Serotonin–norepinephrine reuptake inhibitor

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Findings from clinical trials in humans have shown these antidepressants can help to reduce pain and functional impairment in central and neuropathic pain conditions. This property of SNRIs might be used to reduce doses of other pain relieving medication and lower the frequency of safety, limited efficacy and tolerability issues. Clinical research data have shown in patients with GAD that the SNRI duloxetine is significantly more effective than placebo in reducing pain-related symptoms of GAD, after short-term and long-term treatment. However, findings suggested that such symptoms of physical pain reoccur in relapse situations, which indicates a need for ongoing treatment in patients with GAD and concurrent painful physical symptoms.

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tedizolid, methylene blue, procarbazine, amphetamines, clomipramine, and more. Early symptoms of serotonin syndrome may include nausea, vomiting, diarrhea, sweating, agitation, confusion, muscle rigidity, dilated pupils, hyperthermia, rigidity, and goose bumps. More severe symptoms include fever, seizures, irregular heartbeat, delirium, and coma. If signs or symptoms arise, discontinue treatment with serotonergic agents immediately. It is recommended to washout 4 to 5 half-lives of the serotonergic agent before using an MAO inhibitor.

1147: 4645: 518: 661: 849: 474: 1892: 350: 409: 561: 49: 605: 10401: 1159:-methylation of milnacipran in substituent group R and R reduces the norepinephrine and serotonin activity. Researches on different secondary amides in substitution groups R and R showed that π electrons play an important role in the interaction between transporters and ligands. A phenyl group in substituent R showed effect on norepinephrine transporters. Substituent groups in R and R with 1412:, an area of the brain largely lacking in dopamine transporters. This effect of SNRIs results in increased dopamine neurotransmission, in addition to the increases in serotonin and norepinephrine activity. Furthermore, because SNRIs are extremely selective, they have no measurable effects on other, unintended receptors, in contrast to 864:. This interaction seems to be critical for increased availability of norepinephrine in or near the synaptic clefts. Actions of imipramine-like tricyclic antidepressants have complex, secondary adaptions to their initial and sustained actions as inhibitors of norepinephrine transport and variable blockade of serotonin transport. 286: 1371:. Most SNRIs including venlafaxine, desvenlafaxine, and duloxetine, are several fold more selective for serotonin over norepinephrine, while milnacipran is three times more selective for norepinephrine than serotonin. Elevation of norepinephrine levels is thought to be necessary for an antidepressant to be effective against 1795:

of norepinephrine levels can sometimes cause anxiety, mildly elevated pulse, and elevated blood pressure. However, norepinephrine-selective antidepressants, such as reboxetine and desipramine, have successfully treated anxiety disorders. People at risk for hypertension and heart disease should monitor their blood pressure.

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Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC (December 2007). "Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer

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Most antidepressants, including SNRIs, are safe and effective in the geriatric population. Decisions are often based on co-morbid conditions, drug interactions, and patient tolerance. Due to differences in body composition and metabolism, starting doses are often half that of the recommended dose for

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Because the SNRIs and SSRIs act in similar ways to elevate serotonin levels, they share many side effects, though to varying degrees. The most common side effects include nausea/vomiting, sweating, loss of appetite, dizziness, headache, increase in suicidal thoughts, and sexual dysfunction. Elevation

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in addition to their effect on serotonin and norepinephrine levels. As such, it is possible that an additional mechanism of these drugs that acts in combination with the previously understood mechanism exist. The implication behind these findings suggests use of SNRIs as potential anti-inflammatories

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Several studies have shown that antidepressant drugs which have combined serotonergic and noradrenergic activity are generally more effective than SSRIs, which act upon serotonin reuptake by itself. Serotonergic-noradrenergic antidepressant drugs may have a modest efficacy advantage compared to SSRIs

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to give arylthiomethyl morpholine. Some of the arylthiomethyl morpholine derivatives maintain potent levels of serotonin and norepinephrine reuptake inhibition. Dual serotonin and norepinephrine reuptake inhibition resides in different enantiomers for arylthiomethyl morpholine scaffold. Possible drug

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of these responses may be due to increased exposure to endogenous norepinephrine or from the prolonged occupation of the norepinephrine transport mechanisms (via an allosteric effect). The adaptation allows the presynaptic synthesis and secretion of norepinephrine to return to, or even exceed, normal

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of depression. Symptoms may occur because concentrations of neurotransmitters, such as norepinephrine and serotonin, are insufficient, leading to downstream changes. Medications for depression affect the transmission of serotonin, norepinephrine, and dopamine. Older and less selective antidepressants

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Because SNRIs were developed more recently than SSRIs, there are relatively few of them. However, the SNRIs are among the most widely used antidepressants today. In 2009, Cymbalta and Effexor were the 11th- and 12th-most-prescribed branded drugs in the United States, respectively. This translates to

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A serious, but rare, side effect of SNRIs is serotonin syndrome, which is caused by an excess of serotonin in the body. Serotonin syndrome can be caused by taking multiple serotonergic drugs, such as SSRIs or SNRIs. Other drugs that contribute to serotonin syndrome include MAO inhibitors, linezolid,

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SNRIs are delivered orally, usually in the form of capsules or tablets. It is recommended to take SNRIs in the morning with breakfast, which does not affect drug levels, but may help with certain side effects. Norepinephrine has activating effects in the body and therefore can cause insomnia in some

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provides a more potent inhibitory effect of norepinephrine uptake and improves the selectivity for norepinephrine over the serotonin transporter. Effects of chloro, methoxy and trifluoromethyl substituents in the aromatic ring of cycloalkanol ethylamine scaffold were tested. The results showed that

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Data from clinical trials have indicated that SNRIs might have pain relieving properties. Although the perception and transmission of pain stimuli in the central nervous system have not been fully elucidated, extensive data support a role for serotonin and norepinephrine in the modulation of pain.

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double bond showed significant improved effect on both norepinephrine and serotonin transporters. Studies show that introducing a 2-methyl group in substituent R, the potency at norepinephrine and serotonin transporters are almost abolished. Methyl groups in substituent groups R and R also abolish

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Several reuptake inhibitors contain an aryloxypropanamine scaffold. This structural motif has potential for high affinity binding to biogenic amine transports. Drugs containing an aryloxypropanamine scaffold have selectivity profile for norepinephrine and serotonin transporters that depends on the

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Agents with dual serotonin and norepinephrine reuptake inhibition (SNRIs) are sometimes called non-tricyclic serotonin and norepinephrine reuptake inhibitors. Clinical studies suggest that compounds that increase the concentration in the synaptic cleft of both norepinephrine and serotonin are more

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TCAs were the first medications that had dual mechanism of action. The mechanism of action of tricyclic secondary amine antidepressants is only partly understood. TCAs have dual inhibition effects on norepinephrine reuptake transporters and serotonin reuptake transporters. Increased norepinephrine

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associated particularly with TCAs, and to a lesser extent with SSRIs. Selectivity of antidepressant agents are based on the neurotransmitters that are thought to influence symptoms of depression. Drugs that selectively block the reuptake of serotonin and norepinephrine effectively treat depression

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since 1977. The drug is used to treat acute and chronic pain. It has shown effectiveness in the treatment of fibromyalgia, though it is not specifically approved for this purpose. The drug is also under investigation as an antidepressant and for the treatment of neuropathic pain. It is related in

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Due to the extreme changes in noradrenergic activity produced from norepinephrine and serotonin reuptake inhibition, patients that are just starting an SNRI regimen are usually given lower doses than their expected final dosing to allow the body to acclimate to the drug's effects. As the patient

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activity, pre-existing hypertension should be controlled before treatment with SNRIs and blood pressure periodically monitored throughout treatment. Duloxetine has also been associated with cases of liver failure and should not be prescribed to patients with chronic alcohol use or liver disease.

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Selective serotonin reuptake inhibitors (SSRIs) selectively inhibit the reuptake of serotonin and are a widely used group of antidepressants. With increased receptor selectivity compared to TCAs, undesired effects such as poor tolerability are avoided. Serotonin is synthesized from an amino acid

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in 1994. The reuptake effects of venlafaxine are dose-dependent. At low doses (<150 mg/day), it acts only on serotonergic transmission. At moderate doses (>150 mg/day), it acts on serotonergic and noradrenergic systems, whereas at high doses (>300 mg/day), it also affects

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SSRIs and SNRIs have been shown to be effective in treating major depressive disorder and anxiety in pediatric populations. However, there is a risk of increased suicidality in pediatric populations for treatment of major depressive disorder, especially with venlafaxine. Fluoxetine is the only

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and therefore rapid clearance upon discontinuation. In some cases, switching from venlafaxine to fluoxetine, a long-acting SSRI, and then tapering off fluoxetine, may be recommended to reduce discontinuation symptoms. Signs and symptoms of withdrawal from abrupt cessation of an SNRI include

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of depression, which asserts that decreased concentrations of monoamine neurotransmitters leads to depressive symptoms, the following relations were determined: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; serotonin to anxiety,

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The application of an aryloxypropanamine scaffold has generated a number of potent MAOIs. Before the development of duloxetine, the exploration of aryloxypropanamine structure activity relationships resulted in the identification of fluoxetine and atomoxetine. The same motif can be found in

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mechanism through their effects on presynaptic receptors. One probable explanation for the effects on decreased neurotransmitter release is that, as the receptors activate, inhibition of neurotransmitter release occurs (including suppression of voltage-gated Ca currents and activation of G

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of norepinephrine and serotonin in the brain, which results in higher concentrations of neurotransmitters. Antidepressants that have dual mechanisms of action inhibit the reuptake of both serotonin and norepinephrine and, in some cases, inhibit with weak effect the reuptake of dopamine.

534:(FDA) approved milnacipran for treatment of fibromyalgia in the United States in January 2009, however it is not approved for depression in that country. Milnacipran has been commercially available in Europe and Asia for several years. It was first introduced in France in 1996. 1255:

in treating major depressive disorder (MDD), but are slightly less well tolerated. Further research is needed to examine the possible differences of efficacy in specific MDD sub-populations or for specific MDD symptoms, between these classes of antidepressant drugs.

1923:(brighter presentation of lights or highlighted colors). Evidence shows that 8.9% of those taking SNRIs experienced visual snow, 10.5% experienced palinopsia, 15.3% experienced photophobia, and 17.7% experienced nyctolopia as the result of SNRI prescription intake. 1408:-desmethylvenlafaxine to strongly inhibit serotonin and norepinephrine reuptake in the brain. The evidence also suggests that dopamine and norepinephrine behave in a co-transportational manner, due to the inactivation of dopamine by norepinephrine reuptake in the 1388:

following brain injury or any other disease where swelling of the brain is an issue. However, regardless of the mechanism, the efficacy of these drugs in treating the diseases for which they have been indicated has been proven, both clinically and in practice.

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Recent studies have shown that depression may be linked to increased inflammatory response, thus attempts at finding an additional mechanism for SNRIs have been made. Studies have shown that SNRIs as well as SSRIs have significant anti-inflammatory action on

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and serotonin concentrations are obtained by inhibiting both of these transporter proteins. TCAs have substantially more affinity for norepinephrine reuptake proteins than the SSRIs. This is because of a formation of secondary amine TCA metabolites.

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The active metabolite of venlafaxine. It is believed to work in a similar manner, though some evidence suggests lower response rates compared to venlafaxine and duloxetine. It was introduced by Wyeth in May 2008 and was then the third approved SNRI.

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back into the presynaptic nerve terminal. Dual inhibition of serotonin and noradrenaline reuptake can offer advantages over other antidepressant drugs by treating a wider range of symptoms. They can be especially useful in concomitant chronic or

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Symptoms of SNRI overdose, whether it be a mixed drug interaction or the drug alone, vary in intensity and incidence based on the amount of medicine taken and the individuals sensitivity to SNRI treatment. Possible symptoms may include:

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Mahaney PE, Vu AT, McComas CC, Zhang P, Nogle LM, Watts WL, et al. (December 2006). "Synthesis and activity of a new class of dual acting norepinephrine and serotonin reuptake inhibitors: 3-(1H-indol-1-yl)-3-arylpropan-1-amines".

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chemical structure to venlafaxine. Due to being an opioid, there is risk of abuse and addiction, but it does have less abuse potential, respiratory depression, and constipation compared to other opioids (hydrocodone, oxycodone, etc.).

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in 4' position of the aryloxy ring. Atomoxetine, nisoxetine and reboxetine all have a substitution group in the 2' position and are selective NRIs while compounds that have a substitution group in the 4' position (like fluoxetine and

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Boot J, Cases M, Clark BP, Findlay J, Gallagher PT, Hayhurst L, et al. (February 2005). "Discovery and structure-activity relationships of novel selective norepinephrine and dual serotonin/norepinephrine reuptake inhibitors".

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Milnacipran is structurally different from other SNRIs. The structure activity relationship of milnacipran derivatives at the transporter level is still largely unclear and is based on in vivo efficacy that was reported in 1987.

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protein-coupled receptor-operated K currents). Repeated exposure of agents with this type of mechanism leads to inhibition of neurotransmitter release, but repeated administration of TCAs finally leads to decreased responses by α

714:. Researchers noted that patients given iproniazid became cheerful, more optimistic, and more physically active. Soon after its development, iproniazid and related substances were shown to slow enzymatic breakdown of serotonin, 1856:

Some studies suggest there are risks of upper gastrointestinal bleeding, especially venlafaxine, due to impairment of platelet aggregation and depletion of platelet serotonin levels. Similarly to SSRIs, SNRIs may interact with

1130:. Further synthesis and testing identified WAY-256805, a potent norepinephrine reuptake inhibitor that exhibited excellent selectivity and was efficacious in animal models of depression, pain, and thermoregulatory dysfunction. 5313:

Perahia DG, Pritchett YL, Kajdasz DK, Bauer M, Jain R, Russell JM, et al. (January 2008). "A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder".

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Mahaney PE, Gavrin LK, Trybulski EJ, Stack GP, Vu TA, Cohn ST, et al. (July 2008). "Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors".

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Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E, et al. (October 2002). "Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial".

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and temperature control based on the progression of the serotonin toxicity. Patients are often monitored for vitals and airways cleared to ensure that they are receiving adequate levels of oxygen. Another option is to use

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and other symptoms. Therefore, it is recommended that users seeking to discontinue an SNRI slowly taper the dose under the supervision of a professional. Discontinuation syndrome has been reported to be markedly worse for

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Versiani M, Cassano G, Perugi G, Benedetti A, Mastalli L, Nardi A, Savino M (January 2002). "Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder".

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A systematic review that looked at the efficacy of antidepressants for pain relief concludes that only 11 of 42 comparisons showed evidence of efficacy. Seven of the eleven comparisons belong to the SNRI drug class.

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hypothesis of emotion and its relation to depression was of wide interest and that the decreased levels of certain neurotransmitters, such as norepinephrine, serotonin, and dopamine might play a role in the

7719: 4723:"A meta-analysis of effects of selective serotonin reuptake inhibitors on blood pressure in depression treatment: outcomes from placebo and serotonin and noradrenaline reuptake inhibitor controlled trials" 2477:

Iyengar S, Webster AA, Hemrick-Luecke SK, Xu JY, Simmons RM (November 2004). "Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine reuptake inhibitor in persistent pain models in rats".

5494:"A review of the suitability of duloxetine and venlafaxine for use in patients with depression in primary care with a focus on cardiovascular safety, suicide and mortality due to antidepressant overdose" 4339:

Tynan RJ, Weidenhofer J, Hinwood M, Cairns MJ, Day TA, Walker FR (March 2012). "A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia".

793: 766:, the first SSRI. The improved safety and tolerability profile of the SSRIs in patients with MDD, compared with TCAs and MAOIs, represented yet another important advance in the treatment of depression. 3724:

Vu AT, Cohn ST, Terefenko EA, Moore WJ, Zhang P, Mahaney PE, et al. (May 2009). "3-(Arylamino)-3-phenylpropan-2-olamines as a new series of dual norepinephrine and serotonin reuptake inhibitors".

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Boot JR, Brace G, Delatour CL, Dezutter N, Fairhurst J, Findlay J, et al. (November 2004). "Benzothienyloxy phenylpropanamines, novel dual inhibitors of serotonin and norepinephrine reuptake".

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Fish PV, Deur C, Gan X, Greene K, Hoople D, Mackenny M, et al. (April 2008). "Design and synthesis of morpholine derivatives. SAR for dual serotonin & noradrenaline reuptake inhibition".

8351: 3355:

Nutt DJ, Forshall S, Bell C, Rich A, Sandford J, Nash J, Argyropoulos S (July 1999). "Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders".

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the potency at norepinephrine and serotonin transporters. Researchers found that replacing one of the ethyl groups of milnacipran with an allyl moiety increases the norepinephrine potency. The

991:. With administration of SNRIs, neuronal activity in locus coeruleus region is induced because of increased concentration of norepinephrine in the synaptic cleft. This results in activation of 421:

in August 2004. Duloxetine is contraindicated in patients with heavy alcohol use or chronic liver disease, as duloxetine can increase the levels of certain liver enzymes that can lead to acute

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Tamiya J, Dyck B, Zhang M, Phan K, Fleck BA, Aparicio A, et al. (June 2008). "Identification of 1S,2R-milnacipran analogs as potent norepinephrine and serotonin transporter inhibitors".

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Cashman JR, Ghirmai S (October 2009). "Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression".

789:. In contrast with several other antidepressant drugs, venlafaxine can induce a rapid onset of action mainly due to a subsequent norepinephrine reuptake inhibition. See timeline in figure 1. 3207:

Brunello N, Mendlewicz J, Kasper S, Leonard B, Montgomery S, Nelson J, et al. (October 2002). "The role of noradrenaline and selective noradrenaline reuptake inhibition in depression".

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fused at the 2' and 3' positions, therefore it has dual selective norepinephrine and serotonin reuptake inhibitory effects and has similar potencies for both transporters. The nature of the

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patients if taken at bedtime. SNRIs can also cause nausea, which is usually mild and goes away within a few weeks of treatment, but taking the medication with food can help alleviate this.

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No antidepressants are FDA approved during pregnancy. Use of antidepressants during pregnancy may result in fetus abnormalities affecting functional development of the brain and behavior.

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Redrobe JP, Bourin M, Colombel MC, Baker GB (July 1998). "Dose-dependent noradrenergic and serotonergic properties of venlafaxine in animal models indicative of antidepressant activity".

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Chen C, Dyck B, Fleck BA, Foster AC, Grey J, Jovic F, et al. (February 2008). "Studies on the SAR and pharmacophore of milnacipran derivatives as monoamine transporter inhibitors".

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should not be prescribed SNRIs. Duloxetine and milnacipran are also contraindicated in patients with uncontrolled narrow-angle glaucoma, as they have been shown to increase incidence of

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purposes. Sibutramine was the first drug for the treatment of obesity to be approved in 30 years. It has been associated with increased cardiovascular events and strokes and has been

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Overdosing on SNRIs can be caused by either drug combinations or excessive amounts of the drug itself. Venlafaxine is marginally more toxic in overdose than duloxetine or the SSRIs.

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is about 5 hours, and with once-daily dosing, steady-state concentration is achieved after about 3 days, though its active metabolite desvenlafaxine lasts longer. The half-life of

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Inhibiting the reuptake transport protein results in increased concentrations of serotonin and norepinephrine in the synaptic clefts, leading to improvement of depression symptoms.

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successful than single acting agents in the treatment of depression, but the data is not conclusive whether SNRIs are a more effective treatment option over SSRIs for depression.

1839:(Stendra), have sometimes been helpful to decrease the sexual dysfunction, including erectile dysfunction, although they have been shown to be more effective in men than women. 840:

and are better tolerated than TCAs. TCAs have comprehensive effects on various neurotransmitters receptors, which leads to lack of tolerability and increased risk of toxicity.

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Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J (2018). "Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review".

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Stahl SM, Grady MM, Moret C, Briley M (September 2005). "SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants".

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Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH (August 2006). "Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor".

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levels of norepinephrine in the synaptic clefts. Overall, inhibition of norepinephrine reuptake induced by TCAs leads to decreased rates of neuron firing (mediated through α

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continues along at low doses without any side-effects, the dose is incrementally increased until the patient sees improvement in symptoms without detrimental side-effects.

7705: 2151: 967:. Serotonergic pathways are classified into two main ways in the brain: the ascending projections from the medial and dorsal raphe and the descending projections from the 3080:

Ruelas EG, Diaz-Martinez A, Ruiz RM, Study TV, Group C (1997). "An open assessment of the acceptability, efficacy, and tolerance of venlafaxine in usual care settings".

1706:, which can be life-threatening. Other drugs and substances that should be avoided due to increased risk of serotonin syndrome when combined with an SNRI include: other 17: 2528:

Hunziker ME, Suehs BT, Bettinger TL, Crismon ML (August 2005). "Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder".

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TCAs do not block dopamine transport directly but might facilitate dopaminergic effects indirectly by inhibiting dopamine transport into noradrenergic terminals of the

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isomer of milnacipran. Under development for the treatment of depression in the United States and Canada, it was approved by the FDA for treatment of MDD in July 2013.

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candidates with dual serotonin and norepinephrine reuptake inhibitory activity have also been derived from piperazine, 3-amino-pyrrolidine and benzylamine templates.

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Troy SM, Parker VP, Hicks DR, Pollack GM, Chiang ST (October 1997). "Pharmacokinetics and effect of food on the bioavailability of orally administered venlafaxine".

449:. Caution should be taken when taking Duloxetine with other medications that are metabolized by CYP 2D6 as this may precipitate a potential drug-drug interaction. 2446:

Perry R, Cassagnol M (June 2009). "Desvenlafaxine: a new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder".

2083:), an SSRI. In some studies, SNRIs demonstrated slightly higher antidepressant efficacy than the SSRIs (response rates 63.6% versus 59.3%). However, in one study 1223:

enzymes is thought to be an attractive feature because many of the central nervous system drugs are highly lipophilic and are mainly eliminated by liver enzymes.

8043: 6131: 5612:"Escitalopram in the treatment of major depressive disorder: clinical efficacy, tolerability and cost-effectiveness vs. venlafaxine extended-release formulation" 1090:

substituent also has a significant influence on the activity and selectivity of the compounds as inhibitors of the serotonin or the norepinephrine transporters.

10269: 8386: 3962:"The short- and long-term effect of duloxetine on painful physical symptoms in patients with generalized anxiety disorder: results from three clinical trials" 1404:

in order to inhibit reuptake of serotonin, norepinepherine, and marginal amounts of dopamine. For example, venlafaxine works alongside its primary metabolite

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Tint A, Haddad PM, Anderson IM (May 2008). "The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study".

3112:

Grandoso L, Pineda J, Ugedo L (May 2004). "Comparative study of the effects of desipramine and reboxetine on locus coeruleus neurons in rat brain slices".

1865:. There is more evidence of SSRIs having higher risk of bleeding than SNRIs. Studies have suggested caution when using SNRIs or SSRIs with high doses of 1815:), which are usually somewhat milder with SNRIs compared to SSRIs. To manage sexual dysfunction, studies have shown that switching to or augmenting with 781:. These substances are unrelated to TCA and other SSRIs. Venlafaxine blocks the neuronal reuptake of serotonin, noradrenaline, and, to a lesser extent, 2313:

Spina E, Santoro V, D'Arrigo C (July 2008). "Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update".

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The condition for which SNRIs are mostly indicated, major depressive disorder, was thought to be mainly caused by decreased levels of serotonin and

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Since the late 1980s, SSRIs have dominated the antidepressant drug market. Today, there is increased interest in antidepressant drugs with broader

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or other diseases in certain at risk patients. The risk of liver damage appears to be only for patients already at risk, unlike the antidepressant

9466: 6098: 5006: 1754:, autonomic instability with fluctuating vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. 777:, a serotonin–norepinephrine reuptake inhibitor. Venlafaxine was the first compound described in a new class of antidepressive substances called 3876:

Nemeroff CB, Thase ME (2007). "A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients".

269:. Since their introduction in the late 1980s, second-generation antidepressants have largely replaced first-generation antidepressants, such as 2619: 1044:

The non-tricyclic SNRIs have several important differences that are based on pharmacokinetics, metabolism to active metabolites, inhibition of

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being the latest drug to be developed in 2013. The drugs vary by their other medical uses, chemical structure, adverse effects, and efficacy.

5585: 10331: 9873: 9868: 9149: 9144: 8963: 7390: 7375: 7305: 6913: 6164: 734:(TCA). Imipramine was found to affect numerous neurotransmitter systems and to block the reuptake of norepinephrine and serotonin from the 8036: 1900: 153: 3041: 2947:"Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial" 1219:

interaction, moderate tissue distribution and a reasonably long elimination half-life. Milnacipran's lack of drug-drug interactions via

1122:-trifluoromethyl analogue exhibited the most potent inhibitory effect of norepinephrine and the most selectivity over serotonin uptake. 9652: 1127: 5195:"Use of SSRI, But Not SNRI, Increased Upper and Lower Gastrointestinal Bleeding: A Nationwide Population-Based Cohort Study in Taiwan" 2829: 1416:

inhibition. Pharmaceutical tests have determined that use of both SNRIs or SSRIs can generate significant anti-inflammatory action on

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obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life." SNRIs work by

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substitution pattern of the aryloxy ring. Selective NRIs contain a substituent in 2' position of the aryloxy ring but SSRIs contain a

10249: 9990: 8381: 8376: 5915: 939:. Because they affect so many different receptors, TCAs have adverse effects, poor tolerability, and an increased risk of toxicity. 10374: 4594:"A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder" 195: 4132: 1774:

should caution the use of SNRIs. Furthermore, due to some SNRIs' actions on obesity, patients with major eating disorders such as

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SNRIs, similarly to SSRIs, can cause several types of sexual dysfunction, such as erectile dysfunction, decreased libido, sexual

693: 4517: 4482: 4447: 2644: 2586: 8371: 8029: 2146: 231: 4959:"Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and potential solutions: A narrative literature review" 7663: 7026: 6970: 445:. Duloxetine also undergoes hepatic metabolism and has been shown to cause inhibition of the hepatic cytochrome P450 enzyme 10358: 6197: 2061:

Overdose is usually treated symptomatically, especially in the case of serotonin syndrome, which requires treatment with

1866: 738:, therefore increasing the levels of these neurotransmitters. Use of MAOIs and TCAs gave major advances in treatment of 8724: 6065: 3508: 1007: 773:

that may offer improvements in efficacy and tolerability. In 1993, a new drug was introduced to the US market called

235: 199: 10173: 7680: 6987: 5708:"The Impact of Antidepressant Dose and Class on Treatment Response in Pediatric Anxiety Disorders: A Meta-Analysis" 266: 2771: 2270:

Wright ME, Rizzolo D (March 2017). "An update on the pharmacologic management and treatment of neuropathic pain".

2198:"SNRIs: The Pharmacology, Clinical Efficacy, and Tolerability in Comparison with Other Classes of Antidepressants" 2673:

Frampton JE, Plosker GL (2007). "Duloxetine: a review of its use in the treatment of major depressive disorder".

483: 429:, which, though rare, can spontaneously cause liver failure in healthy patients. Duloxetine is also approved for 4334: 4332: 277:(MAOIs), as the drugs of choice for the treatment of MDD due to their improved tolerability and safety profile. 10378: 7100: 726:, or MAOIs. During this time development of distinctively different antidepressant agents was also researched. 2772:"Meridia (sibutramine hydrochloride monohydrate) Capsules C-IV. Full Prescribing Information (archived label)" 9434: 7796: 5908: 4329: 1958: 1811:. The two common sexual side effects are diminished interest in sex (libido) and difficulty reaching climax ( 1300: 1282: 673:

dopaminergic neurotransmission. At small doses, venlafaxine has also been shown to be effective in treating

10354: 8071: 8052: 7435: 1974:

is related to venlafaxine, the same conditions apply. This is likely due to venlafaxine's relatively short

1288: 531: 434: 207: 5850:"Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews" 5848:

Ferreira GE, Abdel-Shaheed C, Underwood M, Finnerup NB, Day RO, McLachlan A, et al. (February 2023).

9718: 8994: 7420: 6570: 6503: 5400:"Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review" 1699: 1018: 1011: 992: 723: 678: 274: 3449:"The role of selective serotonin reuptake inhibitors in preventing relapse of major depressive disorder" 2613:"Yentreve (duloxetine hydrochloride) Hard Gastro-Resistant Capsules. Summary of Product Characteristics" 10391: 8713: 8225: 6333: 6241: 4656:. University of North Carolina at Chapel Hill and the United States National Institute of Mental Health 1747: 1350:

in the synaptic cleft, causing erratic signaling. This theory, however, has been refuted. Based on the

924: 250: 112: 7697: 4548:"Serotonin-norepinephrine reuptake inhibitors and the influence of binding affinity (Ki) on analgesia" 568:

An SNRI, which, instead of being developed for the treatment of depression, was widely marketed as an

7877: 7770: 7405: 7019: 6345: 4927:

Clayton AH, Montejo AL (2006). "Major depressive disorder, antidepressants, and sexual dysfunction".

2141: 1979:

dizziness, anxiety, insomnia, nausea, sweating, and flu-like symptoms, such as lethargy and malaise.

1376: 1276: 430: 270: 246: 175: 1682:

is about 11 hours, and steady-state concentrations are achieved after 4 to 5 days. The half-life of

7954: 5901: 731: 527: 124: 4223:

Nutt DJ (2008). "Relationship of neurotransmitters to the symptoms of major depressive disorder".

2793:

Luque CA, Rey JA (April 2002). "The discovery and status of sibutramine as an anti-obesity drug".

1690:

has a half-life of about 6 to 8 hours, and steady-state levels are reached within 36 to 48 hours.

10191: 7668: 6975: 4592:

Upadhyaya HP, Desaiah D, Schuh KJ, Bymaster FP, Kallman MJ, Clarke DO, et al. (March 2013).

3157:"Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" 2834: 2136: 1771: 1294: 964: 867:

Norepinephrine interacts with postsynaptic α and β adrenergic receptor subtypes and presynaptic α

577: 1823:

have decreased symptoms of sexual dysfunction. Studies have shown that PDE5 Inhibitors, such as

10370: 10366: 9773: 9049: 8479: 8432: 6810: 6281: 5291: 4518:"Savella- milnacipran hydrochloride tablet, film coated Savella- milnacipran hydrochloride kit" 880: 786: 2172: 1113:

contain a cycloalkanol ethylamine scaffold. Increasing the electron-withdrawing nature of the

9491: 9423: 8897: 8199: 6251: 3056: 1401: 1025: 242: 187: 108: 4264: 4247: 2839: 1055:

Combination of mechanisms of action in a single active agent is an important development in

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are thought to play an important role in mood regulation. SNRIs can be contrasted with the

4785:

Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, et al. (July 2018).

4156:

Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA (2022-07-20).

2350:"A brief history of the development of antidepressant drugs: from monoamines to glutamate" 473: 8: 10048: 9893: 9758: 9486: 9343: 9169: 9034: 8689: 8464: 7820: 7735: 6756: 6696: 4397:

Lambert O, Bourin M (November 2002). "SNRIs: mechanism of action and clinical features".

2945:

Joffe H, Guthrie KA, LaCroix AZ, Reed SD, Ensrud KE, Manson JE, et al. (July 2014).

1397: 397: 385: 4192: 4157: 4001:"SNRIs pharmacological alternatives for the treatment of obsessive compulsive disorder?" 2719:

Morishita S, Arita S (February 2003). "The clinical use of milnacipran for depression".

1686:

is about 12 hours (range: 8–17 hours), and steady-state is achieved after about 3 days.

1171:

The conformation of milnacipran is an important part of its pharmacophore. Changing its

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ring system. Some studies have been made where the oxygen in reboxetine is replaced by

1056: 983:

Noradrenergic neurons are located in two major regions in the brain. These regions are

674: 211: 3368: 3220: 3093: 2920: 2806: 2732: 2326: 1133: 580:

from the market in several countries and regions including the United States in 2010.

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affects the norepinephrine and serotonin concentration. Milnacipran is marketed as a

988: 915: 778: 739: 719: 703: 103: 80: 5785: 5478: 4707: 4426: 4369: 4069: 3913:"Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise" 3862: 3384: 3282: 3141: 3023: 2962: 2890: 2702: 2541: 2507: 2455: 2429: 907:

receptors also cause decreased intracellular cyclic AMP expression which results in

815:

Antidepressants affect variable neuronal receptors such as muscarinic cholinergic, α

130: 10229: 10084: 9456: 8852: 8549: 8489: 8306: 8220: 7962: 7862: 7728: 7139: 6920: 6863: 6799: 6646: 5869: 5861: 5820: 5812: 5765: 5727: 5719: 5675: 5667: 5623: 5513: 5505: 5456: 5448: 5411: 5370: 5362: 5323: 5263: 5255: 5214: 5206: 5165: 5157: 5107: 5046: 4978: 4970: 4907: 4868: 4806: 4798: 4744: 4734: 4687: 4613: 4605: 4559: 4406: 4349: 4308: 4300: 4259: 4187: 4169: 4104: 4096: 4049: 4012: 3973: 3932: 3924: 3885: 3846: 3842: 3803: 3768: 3733: 3698: 3658: 3618: 3582: 3541: 3468: 3460: 3419: 3411: 3364: 3262: 3236: 3216: 3176: 3168: 3121: 3089: 3003: 2966: 2958: 2916: 2870: 2802: 2748: 2728: 2682: 2537: 2487: 2451: 2409: 2369: 2361: 2322: 2279: 2244: 2209: 2067: 1775: 1372: 1310: 1208: 1200: 956: 418: 259: 254: 227: 183: 179: 4158:"The serotonin theory of depression: a systematic umbrella review of the evidence" 3977: 1199:)-isomer has negative impact on norepinephrine concentration. Milnacipran has low 10405: 10199: 10074: 10016: 10004: 9672: 9311: 8943: 8877: 8291: 8179: 8154: 7940: 7538: 7530: 7520: 7317: 7048: 6859: 6853: 6666: 6040: 5161: 3305:(6th ed.). USA: Lippincott Williams & Wilkins. pp. 547–67, 581–582. 1954: 1779: 1607: 1367:

concentrations of serotonin and norepinephrine and, consequently, an increase in

1363:

of the neurotransmitters serotonin and norepinephrine. This results in increased

1220: 1212: 1180: 1176: 1172: 1045: 984: 936: 896: 828: 806: 454: 298: 8021: 7039: 5928: 5210: 2109:

antidepressant that is approved for child/adolescent major depressive disorder.

408: 10028: 10012: 10008: 9934: 9657: 9323: 9315: 8928: 8694: 8417: 8169: 8006: 7828: 7674: 7510: 7352: 7266: 7114: 7088: 6981: 6423: 6132: 6030: 5924: 5816: 5723: 5542: 5259: 5193:

Cheng YL, Hu HY, Lin XH, Luo JC, Peng YL, Hou MC, et al. (November 2015).

4912: 4895: 4587: 4585: 4583: 4174: 3960:

Beesdo K, Hartford J, Russell J, Spann M, Ball S, Wittchen HU (December 2009).

3928: 3807: 3772: 3737: 3702: 3662: 3545: 2907:

Gutierrez MA, Stimmel GL, Aiso JY (August 2003). "Venlafaxine: a 2003 update".

2062: 1820: 1758: 1727: 1711: 1707: 1679: 1521: 1409: 1347: 1305: 1146: 1110: 836: 832: 438: 327: 223: 168: 5074: 4834: 4609: 4353: 4100: 3586: 3400:"Antidepressant efficacy and side-effect burden: a quick guide for clinicians" 3266: 2248: 2213: 1907:

Similarly to other antidepressants, SNRI medications have been found to cause

1093: 253:

that are responsible for the reuptake of serotonin and noradrenaline from the

10415: 10284: 10068: 10064: 10034: 10000: 9974: 9964: 9919: 9883: 9743: 9687: 9526: 9388: 9368: 9351: 9329: 9250: 9245: 9195: 9159: 9019: 8958: 8684: 8204: 8189: 8149: 7992: 7890: 7886: 7848: 7844: 7783: 7779: 7743: 7619: 7504: 7481: 7299: 7261: 7240: 6871: 6818: 6606: 6478: 6453: 6448: 6388: 6363: 5509: 5366: 5111: 4787:"Comprehensive review of cardiovascular toxicity of drugs and related agents" 4448:"Pristiq Extended-Release- desvenlafaxine succinate tablet, extended release" 4410: 4183: 3464: 3172: 2221: 1924: 1858: 1762: 1364: 1204: 1165: 1114: 908: 884: 876: 754: 616:

and SNRI. It was approved by the FDA in 1995, though it has been marketed in

442: 391: 8301: 8296: 5865: 5671: 4974: 4580: 2491: 2413: 1750:. Signs and symptoms of serotonin syndrome include: hyperthermia, rigidity, 879:

which limit the neurophysiological activity of noradrenergic neurons in the

437:(GAD), diabetic neuropathy, chronic musculoskeletal pain, including chronic 10219: 10114: 10104: 9929: 9924: 9768: 9738: 9626: 9496: 9374: 9286: 9255: 9210: 9205: 9200: 9044: 9014: 8902: 8811: 8771: 8674: 8594: 8484: 8474: 8286: 8281: 8266: 8261: 8240: 7921: 7732: 7589: 7579: 7569: 7548: 7471: 7414: 7369: 7256: 7078: 6916: 6904: 6814: 6721: 6651: 6641: 6493: 6483: 6383: 6378: 6301: 6296: 6276: 6261: 6215: 5977: 5941: 5883: 5834: 5799:

Mulsant BH, Blumberger DM, Ismail Z, Rabheru K, Rapoport MJ (August 2014).

5777: 5741: 5689: 5656:"Risks of using SSRI / SNRI antidepressants during pregnancy and lactation" 5637: 5554: 5527: 5470: 5425: 5384: 5335: 5277: 5228: 5179: 5119: 5060: 4992: 4940: 4880: 4820: 4758: 4699: 4627: 4573: 4418: 4361: 4322: 4273: 4232: 4201: 4118: 4026: 3985: 3946: 3897: 3854: 3815: 3780: 3745: 3710: 3670: 3630: 3594: 3553: 3482: 3433: 3376: 3274: 3228: 3190: 3133: 2980: 2928: 2882: 2814: 2740: 2694: 2549: 2499: 2463: 2421: 2383: 2334: 2291: 2256: 2084: 2080: 2045: 2040: 1315: 1083: 968: 759: 743: 711: 707: 9579:

Selective serotonin reuptake inhibitors and serotonin receptor modulators:

4061: 3911:

Marks DM, Shah MJ, Patkar AA, Masand PS, Park GY, Pae CU (December 2009).

3015: 3007: 10289: 10279: 10224: 10195: 10145: 10089: 10042: 10024: 9959: 9939: 9888: 9878: 9853: 9813: 9808: 9753: 9723: 9702: 9692: 9682: 9642: 9581: 9561: 9551: 9531: 9511: 9471: 9461: 9408: 9337: 9319: 9291: 9276: 9235: 9215: 9164: 9154: 9129: 9089: 9084: 9029: 8999: 8978: 8968: 8953: 8918: 8882: 8847: 8776: 8766: 8756: 8751: 8699: 8679: 8669: 8644: 8624: 8554: 8529: 8504: 8499: 8494: 8459: 8454: 8412: 8407: 8356: 8164: 7976: 7936: 7894: 7856: 7840: 7764: 7599: 7584: 7574: 7552: 7494: 7451: 7429: 7250: 7236: 7184: 7159: 7154: 6834: 6731: 6596: 6531: 6526: 6516: 6473: 6458: 6443: 6433: 6403: 6393: 6266: 6236: 6231: 6177: 6154: 6149: 6121: 6078: 6055: 6045: 5987: 5893: 5801:"A systematic approach to pharmacotherapy for geriatric major depression" 5146:"Bleeding incidence with concomitant use of antidepressants and warfarin" 4872: 4691: 3961: 2035: 2030: 1967: 1920: 1687: 1675: 1585: 1565: 1499: 1106: 1074: 972: 774: 626: 573: 539: 491: 294: 5461: 4739: 1226: 1035: 792: 660: 143: 10338: 10294: 10259: 10186: 10149: 10109: 10079: 10056: 10020: 9969: 9954: 9838: 9823: 9793: 9783: 9778: 9733: 9728: 9667: 9662: 9647: 9621: 9591: 9586: 9571: 9566: 9541: 9536: 9506: 9501: 9481: 9476: 9400: 9379: 9362: 9357: 9240: 9230: 9114: 9099: 9069: 9059: 9054: 9009: 9004: 8938: 8933: 8892: 8872: 8857: 8832: 8816: 8791: 8786: 8664: 8654: 8639: 8584: 8574: 8564: 8544: 8534: 8519: 8514: 8437: 8427: 8422: 8235: 8128: 8123: 8000: 7944: 7900: 7872: 7852: 7836: 7832: 7805: 7760: 7727: 7614: 7542: 7489: 7466: 7461: 7444: 7384: 7342: 7327: 7209: 7164: 7149: 7129: 7124: 7119: 7035: 6952: 6938: 6924: 6830: 6826: 6822: 6776: 6746: 6741: 6736: 6716: 6686: 6676: 6636: 6621: 6601: 6488: 6468: 6438: 6418: 6398: 6358: 6306: 6291: 6286: 6246: 6210: 6182: 6111: 6088: 6083: 6035: 6007: 6002: 5997: 5982: 5972: 5351:"A review of the management of antidepressant discontinuation symptoms" 4771:

McIntyre RS et al. The hepatic safety profile of duloxetine: a review.

4641: 4564: 4547: 3415: 2005: 1928: 1916: 1912: 1891: 1832: 1824: 1812: 1808: 1719: 1683: 1543: 1233: 1079: 960: 949: 892: 811: 763: 727: 699: 677:(hot flashes and night sweats) of menopause and may be as effective as 426: 363: 171: 53: 39: 5847: 5452: 5416: 5399: 5139: 5137: 5028: 5026: 4952: 4950: 4896:"Antidepressants and Sexual Dysfunctions: a Translational Perspective" 4802: 3827: 3825: 3622: 1953:

As with SSRIs, the abrupt discontinuation of an SNRI usually leads to

932:

autoreceptors), metabolic activity, and release of neurotransmitters.

848: 285: 10326: 10274: 10244: 10239: 10159: 10141: 10137: 10094: 10052: 9995: 9944: 9863: 9833: 9697: 9616: 9606: 9601: 9596: 9521: 9516: 9396: 9392: 9281: 9271: 9220: 9139: 9109: 8973: 8923: 8842: 8837: 8806: 8801: 8761: 8659: 8649: 8614: 8539: 8509: 8442: 8402: 8366: 8271: 8256: 8230: 8194: 8184: 8113: 8108: 8103: 8098: 7988: 7984: 7966: 7931: 7866: 7787: 7649: 7644: 7639: 7629: 7609: 7534: 7456: 7399: 7289: 7271: 7246: 7219: 7204: 7199: 7194: 7189: 7134: 7068: 7004: 6840: 6726: 6661: 6656: 6631: 6626: 6616: 6611: 6521: 6463: 6428: 6408: 6373: 6329: 6187: 6144: 6116: 6050: 5992: 2365: 2170: 1975: 1870: 1828: 1804: 1783: 1751: 1731: 1715: 1417: 1384: 422: 219: 191: 96: 7391: 7376: 6165: 6018: 3447:

Clevenger SS, Malhotra D, Dang J, Vanle B, IsHak WW (January 2018).

10313: 10264: 10254: 10153: 10099: 10060: 10038: 9828: 9818: 9611: 9404: 9347: 9333: 9104: 9094: 8796: 8781: 8746: 8604: 8599: 8589: 8559: 8361: 8118: 7996: 7980: 7958: 7948: 7809: 7752: 7624: 7604: 7524: 7337: 7281: 7224: 7214: 7179: 7169: 7144: 7073: 6591: 6547: 6271: 6256: 6099: 5398:

Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J (2018).

5134: 5023: 4947: 4082: 3822: 3324: 2050: 2020: 1971: 1874: 1862: 1836: 1360: 1123: 1087: 782: 747: 715: 585: 215: 203: 5758:

Journal of the American Academy of Child and Adolescent Psychiatry

5712:

Journal of the American Academy of Child and Adolescent Psychiatry

5654:

Dubovicky M, Belovicova K, Csatlosova K, Bogi E (September 2017).

1272:

SNRIs have been tested for treatment of the following conditions:

10119: 9949: 9902: 9898: 9848: 9843: 9798: 9788: 9748: 9677: 9556: 9225: 9178: 9174: 9124: 9119: 9074: 9064: 9024: 8948: 8867: 8629: 8619: 8609: 8579: 8524: 8346: 8341: 8336: 8331: 8326: 8321: 8316: 8276: 8174: 8093: 7594: 7231: 7060: 6413: 5653: 4483:"Effexor XR- venlafaxine hydrochloride capsule, extended release" 4083:

Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W (August 2017).

3327:

Goodman & Gilman's: The Pharmacological Basis of Therapeutics

2341: 1962: 1321: 1207:. Because of these properties, milnacipran exhibits almost ideal 1160: 735: 617: 549: 349: 92: 84: 67: 4155: 10129: 9858: 9803: 9546: 9384: 9134: 9079: 8887: 8634: 8311: 7972: 7793: 7634: 7361: 6137:

Tooltip Noradrenergic and specific serotonergic antidepressants

5960: 5144:

Cochran KA, Cavallari LH, Shapiro NL, Bishop JR (August 2011).

3206: 1237: 1216: 978: 900: 613: 530:

effective in the treatment of depression and fibromyalgia. The

446: 5798: 5007:"Serotonin syndrome: Preventing, recognizing, and treating it" 4857: 2476: 2079:

the 2nd- and 3rd-most-common antidepressants, behind Lexapro (

560: 293:

There are eight FDA approved SNRIs in the United States, with

6328: 5754: 5143: 4721:

Zhong Z, Wang L, Wen X, Liu Y, Fan Y, Liu Z (November 2017).

4591: 4338: 2587:"Cymbalta- duloxetine hydrochloride capsule, delayed release" 2527: 1489: 1475: 1006:

Assays have shown that SNRIs have insignificant penchant for

669: 48: 5312: 4678:

Boyer EW, Shannon M (March 2005). "The serotonin syndrome".

4546:

Raouf M, Glogowski AJ, Bettinger JJ, Fudin J (August 2017).

4545: 3079: 2152:

Serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI)

2070:

in the GI tract in order to absorb excess neurotransmitter.

1931:

have also been reported to worsen or cause symptoms of VSS.

668:

The first and most commonly used SNRI. It was introduced by

10203: 6198: 4784: 3607: 2010: 1743: 604: 88: 72:

Selective Serotonin–noradrenaline reuptake inhibitor; SNaRI

8725: 6066: 5241: 3959: 3446: 2993: 2861:

Keating GM (2006). "Tramadol sustained-release capsules".

1770:

three times above their upper normal limit. Patients with

1137:

Cycloalkanol ethylamine scaffold and agents containing it.

942: 7313: 5438: 5397: 4245: 3831: 3758: 2480:

The Journal of Pharmacology and Experimental Therapeutics

2402:

The Journal of Pharmacology and Experimental Therapeutics

10174: 5491: 4246:

Sindrup SH, Otto M, Finnerup NB, Jensen TS (June 2005).

2399: 2312: 710:

properties while researched as a possible treatment for

5706:

Strawn JR, Mills JA, Sauley BA, Welge JA (April 2018).

3344:(4 ed.). San Francisco: Pearson. pp. 383–384. 3042:"History of the Use of Antidepressants in Primary Care" 2944: 1702:

within the last two weeks due to the increased risk of

722:. For this reason, this class of drugs became known as 9716:

Serotonin–norepinephrine–dopamine reuptake inhibitors:

8992:

Serotonin–norepinephrine–dopamine reuptake inhibitors:

7101: 5705: 4248:"Antidepressants in the treatment of neuropathic pain" 4039: 3325:

Brunton, L.L., Lazo, J.S., Parker, K.L., eds. (2006).

3300: 10389: 9435: 7797: 3910: 3571: 3530: 3252: 2195: 1227:

Future development of structure activity relationship

1168:

of milnacipran derivatives is still largely unclear.

1097:

Aryloxypropanamine scaffold and agents containing it.

1036:

Dual serotonin and norepinephrine reuptake inhibitors

8072: 7436: 7396:

Tooltip Serotonin antagonist and reuptake inhibitors

7381:

Tooltip Serotonin-norepinephrine reuptake inhibitors

6170:

Tooltip Serotonin antagonist and reuptake inhibitors

6023:

Tooltip Serotonin–norepinephrine reuptake inhibitors

5701: 5699: 5540: 4133:"Helpful for chronic pain in addition to depression" 3723: 3501:

Applied Therapeutics: The Clinical Use of Drugs, 11e

3354: 2906: 2196:

Stahl SM, Grady MM, Moret C, Briley M (2014-11-07).

2171:

Cleveland Clinic medical professional (2023-03-05).

1048:

isoforms, effect of drug-drug interactions, and the

7757:

Tooltip Serotonin–norepinephrine reuptake inhibitor

7421: 6504: 6104:

Tooltip Norepinephrine–dopamine reuptake inhibitors

5575:"2009 Top 200 branded drugs by total prescriptions" 4384:"Cambridge University Press - Service Announcement" 4289:"Inflammation in depression: is adiposity a cause?" 3688: 3648: 3397: 3111: 2774:. Abbott Laboratories, North Chicago, IL 60064, USA 1101: 8714: 5649: 5647: 5097: 4252:Basic & Clinical Pharmacology & Toxicology 1660: 1449: 1434: 1062: 718:, and norepinephrine via inhibition of the enzyme 238:(NRIs), which act upon single neurotransmitters. 8051: 7878: 7771: 7406: 6346: 5696: 5035:"Recognition and treatment of serotonin syndrome" 3793: 3339: 3301:Lemke TL, Williams DA, Roche VF, Zito SW (2008). 796:Timeline of development of antidepressant agents. 297:being the first drug to be developed in 1993 and 10413: 6569: 5492:Taylor D, Lenox-Smith A, Bradley A (June 2013). 4956: 4477: 4475: 4473: 4471: 4469: 3154: 2668: 2666: 2087:had a superior efficacy profile to venlafaxine. 1766:Studies have found that Duloxetine can increase 1126:, a piperazine-containing derivative, has shown 194:symptoms. Off-label uses include treatments for 7366:Tooltip Selective serotonin reuptake inhibitors 6906: 5965:Tooltip Selective serotonin reuptake inhibitors 5644: 5609: 4720: 4541: 4539: 2830:"Abbott Pulls Diet Drug Meridia Off US Shelves" 2672: 2581: 2579: 2347: 2164: 1877:due to an increased risk of upper GI bleeding. 1215:, low inter-subject variability, limited liver 1128:norepinephrine and dopamine reuptake inhibition 4926: 4893: 3998: 2718: 2577: 2575: 2573: 2571: 2569: 2567: 2565: 2563: 2561: 2559: 2445: 2395: 2393: 2234: 1911:, a condition characterized by visual static, 1191:and substitution of the phenyl group in the (1 1067: 1000: 835:, leading to decreased cardiac conduction and 762:of depression. This led to the development of 9640:Serotonin–norepinephrine reuptake inhibitors: 9424: 8916:Serotonin–norepinephrine reuptake inhibitors: 8744:Selective norepinephrine reuptake inhibitors: 8037: 8008: 7713: 7020: 5909: 5254:(3). National Institutes of Health: 209–217. 5192: 4673: 4671: 4552:Journal of Clinical Pharmacy and Therapeutics 4512: 4510: 4508: 4506: 4504: 4466: 4442: 4440: 4438: 4436: 4396: 4286: 3875: 3498: 3494: 3492: 2940: 2938: 2827: 2766: 2764: 2762: 2760: 2758: 2663: 2637: 2269: 2147:Selective serotonin reuptake inhibitor (SSRI) 1867:nonsteroidal anti-inflammatory drugs (NSAIDs) 1698:SNRIs are contraindicated in patients taking 1656: 1444: 1430: 651:Vasomotor symptoms of menopause (hot flashes) 417:Approved for the treatment of depression and 10422:Serotonin–norepinephrine reuptake inhibitors 8830:Norepinephrine–dopamine reuptake inhibitors: 8061: 4677: 4536: 4216: 3796:Bioorganic & Medicinal Chemistry Letters 3761:Bioorganic & Medicinal Chemistry Letters 3726:Bioorganic & Medicinal Chemistry Letters 3691:Bioorganic & Medicinal Chemistry Letters 3651:Bioorganic & Medicinal Chemistry Letters 3534:Bioorganic & Medicinal Chemistry Letters 3035: 3033: 2902: 2900: 2714: 2712: 2354:Experimental and Clinical Psychopharmacology 979:Selective norepinephrine reuptake inhibitors 883:. Formation of norepinephrine is reduced by 843: 810:like TCAs and MAOIs inhibit the reuptake or 161:Serotonin–norepinephrine reuptake inhibitors 7306: 6940: 6757: 6697: 6203:Tooltip Serotonin modulator and stimulators 5348: 4640: 3567: 3565: 3563: 3202: 3200: 3107: 3105: 3103: 2618:. European Medicines Agency. Archived from 2556: 2523: 2521: 2519: 2517: 2470: 2390: 1948: 1939: 1901:hallucinogen persisting perception disorder 1895:Image depicting the vision of someone with 154:Selective norepinephrine reuptake inhibitor 33:Serotonin–norepinephrine reuptake inhibitor 18:Serotonin norepinephrine reuptake inhibitor 8730:Tooltip Norepinephrine reuptake inhibitors 8044: 8030: 7720: 7706: 7027: 7013: 6071:Tooltip Norepinephrine reuptake inhibitors 5923: 5916: 5902: 5616:International Journal of Clinical Practice 5498:Therapeutic Advances in Psychopharmacology 5355:Therapeutic Advances in Psychopharmacology 5248:Current Neurology and Neuroscience Reports 5235: 4668: 4654:Psychoactive Drug Screening Program (PDSP) 4501: 4433: 3489: 3453:Therapeutic Advances in Psychopharmacology 3320: 3318: 3316: 3314: 3312: 2935: 2755: 2228: 1970:when compared to other SNRIs. As such, as 1332: 5873: 5824: 5731: 5679: 5627: 5541:Simon LV, Hashmi MF, Keenaghan M (2019). 5517: 5460: 5415: 5374: 5267: 5218: 5169: 5050: 4982: 4911: 4810: 4748: 4738: 4617: 4563: 4312: 4263: 4191: 4173: 4108: 4016: 3936: 3684: 3682: 3680: 3472: 3423: 3180: 3039: 3030: 2970: 2897: 2828:Rockoff JD, Dooren JC (October 8, 2010). 2709: 2373: 2348:Hillhouse TM, Porter JH (February 2015). 10179:Tooltip Vesicular monoamine transporters 9454:Selective serotonin reuptake inhibitors: 6798: 3560: 3303:Foye's principles of medicinal chemistry 3296: 3294: 3292: 3248: 3246: 3197: 3100: 3049:Primary Care Companion J Clin Psychiatry 2792: 2514: 1890: 1232:reboxetine where it is constrained in a 1145: 1132: 1092: 847: 791: 742:but their use was limited by unpleasant 284: 196:attention-deficit hyperactivity disorder 7049: 4265:10.1111/j.1742-7843.2005.pto_96696601.x 3644: 3642: 3640: 3526: 3524: 3522: 3520: 3309: 2860: 2441: 2439: 1179:. Effects of milnacipran reside in the 943:Selective serotonin reuptake inhibitors 694:Development and discovery of SSRI drugs 232:selective serotonin reuptake inhibitors 14: 10414: 7106:Tooltip positive allosteric modulators 7089: 7034: 5610:Llorca PM, Fernandez JL (April 2007). 4727:Neuropsychiatric Disease and Treatment 3677: 3503:. Wolters Kluwer. pp. 1813–1833. 3073: 2090: 2073: 1646: 1461: 800: 265:SNRIs, along with SSRIs and NRIs, are 9440:Tooltip Serotonin reuptake inhibitors 8025: 7802:Tooltip monoamine reuptake inhibitors 7701: 7008: 6893: 6797: 6568: 6327: 5940: 5897: 5032: 4085:"Effects of Antidepressants on Sleep" 3329:(11 ed.). New York: McGraw-Hill. 3289: 3243: 2786: 1842: 1798: 8077:Tooltip Dopamine reuptake inhibitors 7441:Tooltip Monoamine oxidase inhibitors 5584:. www.drugtopics.com. Archived from 4957:Jing E, Straw-Wilson K (July 2016). 4894:Olivier JD, Olivier B (2019-09-01). 4222: 4005:Innovations in Clinical Neuroscience 3999:Sansone RA, Sansone LA (June 2011). 3637: 3575:Bioorganic & Medicinal Chemistry 3517: 3348: 2436: 2237:Bioorganic & Medicinal Chemistry 1693: 1423: 860:In addition, the TCAs interact with 753:Throughout the 1960s and 1970s, the 390:Chronic musculoskeletal pain (e.g., 7426:Tooltip Tetracyclic antidepressants 6509:Tooltip Tetracyclic antidepressants 5349:Wilson E, Lader M (December 2015). 5244:"Visual Snow: Updates on Pathology" 5242:Curr Neurol, Neurosci Rep. (2022). 4680:The New England Journal of Medicine 3398:Santarsieri D, Schwartz TL (2015). 2821: 1669: 1391: 1375:, a property shared with the older 1118:the strongest electron-withdrawing 1082:) are SSRIs. Duloxetine contains a 911:relaxation or decreased secretion. 730:became the first clinically useful 24: 9774:Didesmethylsibutramine (BTS-54505) 9050:Didesmethylsibutramine (BTS-54505) 8719:Tooltip Norepinephrine transporter 8480:Didesmethylsibutramine (BTS-54505) 5582:SDI/Verispan, VONA, full year 2009 4929:The Journal of Clinical Psychiatry 4861:The Journal of Clinical Psychiatry 4399:Expert Review of Neurotherapeutics 4293:Dialogues in Clinical Neuroscience 4225:The Journal of Clinical Psychiatry 4054:10.1002/j.1552-4604.1997.tb04270.x 3717: 2284:10.1097/01.JAA.0000512228.23432.f7 1880: 1244: 891:, an effect mediated by decreased 659: 603: 559: 516: 472: 407: 348: 236:norepinephrine reuptake inhibitors 27:Class of antidepressant medication 25: 10433: 8292:Etybenzatropine (ethybenztropine) 7883:Tooltip Tricyclic antidepressants 7776:Tooltip Tricyclic antidepressants 7411:Tooltip Tricyclic antidepressants 6894: 6351:Tooltip Tricyclic antidepressants 2645:"Nefazodone hydrochloride tablet" 1961:", which could include states of 1642: 1638: 1457: 1341: 887:through the rate-limiting enzyme 267:second-generation antidepressants 10399: 9764:Desmethylsibutramine (BTS-54354) 9040:Desmethylsibutramine (BTS-54354) 8470:Desmethylsibutramine (BTS-54354) 5770:10.1097/00004583-200210000-00010 5629:10.1111/j.1742-1241.2007.01335.x 5441:Psychotherapy and Psychosomatics 5404:Psychotherapy and Psychosomatics 5328:10.1016/j.jpsychires.2007.01.008 4305:10.31887/DCNS.2011.13.1/rshelton 4042:Journal of Clinical Pharmacology 3890:10.1016/j.jpsychires.2005.07.009 3357:European Neuropsychopharmacology 3209:European Neuropsychopharmacology 3126:10.1016/j.neuropharm.2003.11.033 2875:10.2165/00003495-200666020-00006 2795:European Journal of Pharmacology 2687:10.2165/00023210-200721070-00004 1757:Due to the effects of increased 1379:(TCAs), but not with the SSRIs. 1102:Cycloalkanol ethylamine scaffold 805:Monoamines are connected to the 47: 10375:Monoamine metabolism modulators 5841: 5792: 5748: 5603: 5567: 5534: 5485: 5432: 5391: 5342: 5316:Journal of Psychiatric Research 5306: 5284: 5186: 5091: 5067: 4999: 4920: 4887: 4851: 4827: 4778: 4765: 4714: 4634: 4604:(2). Springer Nature: 189–200. 4390: 4376: 4280: 4239: 4149: 4125: 4076: 4033: 3992: 3953: 3904: 3878:Journal of Psychiatric Research 3869: 3787: 3752: 3601: 3440: 3391: 3340:Silverthorn, D.U., ed. (2007). 3333: 3155:Pacher P, Kecskemeti V (2004). 3148: 2987: 2963:10.1001/jamainternmed.2014.1891 2854: 2605: 2542:10.1016/j.clinthera.2005.08.010 2456:10.1016/j.clinthera.2009.07.012 2142:Serotonin releasing agent (SRA) 1789: 1327: 1063:Structure activity relationship 959:system regulates the uptake of 5292:"Duloxetine: Drug Information" 4773:Expert Opin Drug Metab Toxicol 4287:Shelton RC, Miller AH (2011). 3847:10.1016/j.biopsych.2007.03.027 3611:Journal of Medicinal Chemistry 2306: 2263: 2189: 1934: 1761:levels and, therefore, higher 1396:Most SNRIs function alongside 1267: 1141: 875:receptors include presynaptic 706:agent, was discovered to have 280: 13: 1: 10355:Receptor/signaling modulators 9429:Tooltip Serotonin transporter 8053:Monoamine reuptake inhibitors 5805:Clinics in Geriatric Medicine 5100:Journal of Psychopharmacology 4900:Current Sexual Health Reports 4342:Brain, Behavior, and Immunity 3978:10.1016/j.janxdis.2009.07.008 3499:Zeind C, Carvalho MG (2018). 3369:10.1016/S0924-977X(99)00030-9 3221:10.1016/s0924-977x(02)00057-3 3161:Current Pharmaceutical Design 3094:10.1016/S0011-393X(97)80088-4 2921:10.1016/s0149-2918(03)80210-2 2807:10.1016/S0014-2999(02)01423-1 2733:10.1016/S0924-9338(02)00003-2 2327:10.1016/S0149-2918(08)80047-1 2157: 2112: 2103: 2056: 1301:Obsessive compulsive disorder 1283:Posttraumatic stress disorder 1249: 208:monoamine reuptake inhibitors 200:obsessive–compulsive disorder 9269:Tetracyclic antidepressants: 8066:Tooltip Dopamine transporter 6571:Monoamine oxidase inhibitors 5660:Interdisciplinary Toxicology 5162:10.1097/FTD.0b013e318224996e 3966:Journal of Anxiety Disorders 3082:Current Therapeutic Research 2095: 1919:(poor vision at night), and 1289:Generalized anxiety disorder 1258: 724:monoamine oxidase inhibitors 639:Generalized anxiety disorder 532:Food and Drug Administration 435:generalized anxiety disorder 382:Generalized anxiety disorder 275:monoamine oxidase inhibitors 7: 9719:3,3-Diphenylcyclobutanamine 8995:3,3-Diphenylcyclobutanamine 6765:Tooltip Monoamine oxidase B 6705:Tooltip Monoamine oxidase A 6334:tetracyclic antidepressants 5211:10.1097/MD.0000000000002022 5150:Therapeutic Drug Monitoring 4963:The Mental Health Clinician 2130: 2121: 1995: 1982: 1851: 1068:Aryloxypropanamine scaffold 1052:of the nontricyclic SNRIs. 746:and significant safety and 679:hormone replacement therapy 398:Stress urinary incontinence 289:Timeline of approved SNRIs. 251:membrane transport proteins 10: 10438: 10359:Monoamine releasing agents 9917:Tricyclic antidepressants: 9193:Tricyclic antidepressants: 8262:Benzatropine (benztropine) 6242:Dextromethorphan/bupropion 5817:10.1016/j.cger.2014.05.002 5724:10.1016/j.jaac.2018.01.015 5260:10.1007/s11910-022-01182-x 4913:10.1007/s11930-019-00205-y 4791:Medicinal Research Reviews 4175:10.1038/s41380-022-01661-0 4089:Current Psychiatry Reports 3929:10.2174/157015909790031201 3808:10.1016/j.bmcl.2008.03.050 3773:10.1016/j.bmcl.2004.08.005 3738:10.1016/j.bmcl.2009.03.054 3703:10.1016/j.bmcl.2008.04.025 3663:10.1016/j.bmcl.2008.01.011 3546:10.1016/j.bmcl.2004.11.025 3055:(S7): 6–10. Archived from 2450:. 31 Pt 1 (1): 1374–1404. 1884: 691: 687: 182:, social phobia, chronic 150: 113:Norepinephrine transporter 10347: 10303: 10172: 9983: 9912: 9711: 9635: 9449: 9422: 9300: 9264: 9188: 8987: 8911: 8825: 8739: 8712: 8395: 8249: 8213: 8137: 8086: 8059: 7955:NMDA receptor antagonists 7909: 7819: 7742: 7658: 7562: 7503: 7480: 7351: 7298: 7280: 7087: 7047: 6965: 6900: 6889: 6806: 6793: 6755: 6695: 6581: 6577: 6564: 6540: 6502: 6344: 6340: 6323: 6224: 6196: 6163: 6130: 6097: 6064: 6016: 5958: 5954: 5936: 5549:. StatPearls Publishing. 5039:Canadian Family Physician 4610:10.1007/s00213-013-2986-z 4354:10.1016/j.bbi.2011.12.011 4101:10.1007/s11920-017-0816-4 3917:Current Neuropharmacology 3587:10.1016/j.bmc.2006.08.039 3267:10.1017/S1092852900019726 2249:10.1016/j.bmc.2009.08.025 2214:10.1017/S1092852900019726 1987: 1724:anti-migraine medications 1628: 1453: 1448: 1443: 1440: 1377:tricyclic antidepressants 1277:Major depressive disorder 1150:Structure of milnacipran. 844:Tricyclic antidepressants 636:Major depressive disorder 508:Major depressive disorder 464:Major depressive disorder 431:major depressive disorder 376:Major depressive disorder 340:Major depressive disorder 271:tricyclic antidepressants 247:noradrenaline transporter 176:major depressive disorder 142: 137: 123: 118: 102: 76: 66: 61: 46: 37: 32: 9643:Atomoxetine (tomoxetine) 8919:Atomoxetine (tomoxetine) 6948:Rubidium chloride (RbCl) 5510:10.1177/2045125312472890 5367:10.1177/2045125315612334 5112:10.1177/0269881107081550 4644:, Driscol J (Dec 2012). 4411:10.1586/14737175.2.6.849 3465:10.1177/2045125317737264 3173:10.2174/1381612043383872 1959:discontinuation syndrome 1949:Discontinuation syndrome 1940:Starting an SNRI regimen 1915:(negative after image), 732:tricyclic antidepressant 152:Not to be confused with 56:, an example of an SNRI. 10021:mepyramine (pyrilamine) 7058:Tooltip 5-HT1A receptor 6811:Atypical antipsychotics 5866:10.1136/bmj-2022-072415 5672:10.1515/intox-2017-0004 4975:10.9740/mhc.2016.07.191 2835:The Wall Street Journal 2492:10.1124/jpet.104.070656 2414:10.1124/jpet.106.103382 2137:List of antidepressants 1772:coronary artery disease 1333:Route of administration 1295:Social anxiety disorder 1211:in humans such as high 642:Social anxiety disorder 10295:Vanoxerine (GBR-12909) 10142:pethidine (meperidine) 9397:pethidine (meperidine) 8185:Pethidine (meperidine) 7098:Tooltip GABAA receptor 5075:"SNRI Antidepressants" 4835:"SNRI Antidepressants" 2951:JAMA Internal Medicine 1904: 1151: 1138: 1098: 881:central nervous system 853: 797: 787:central nervous system 664: 648:Chronic pain syndromes 608: 595:Acute and chronic pain 564: 522: 478: 413: 353: 290: 206:prevention. SNRIs are 10379:Monoamine neurotoxins 9945:Dosulepin (dothiepin) 9492:Didesmethylcitalopram 9221:Dosulepin (dothiepin) 8898:Serdexmethylphenidate 8200:Serdexmethylphenidate 5033:Frank C (July 2008). 3835:Biological Psychiatry 3040:Lieberman JA (2003). 3008:10.1007/s002130050638 2909:Clinical Therapeutics 2530:Clinical Therapeutics 2448:Clinical Therapeutics 2315:Clinical Therapeutics 1894: 1402:secondary metabolites 1149: 1136: 1096: 851: 795: 663: 607: 563: 520: 476: 411: 352: 288: 243:serotonin transporter 210:; specifically, they 188:fibromyalgia syndrome 109:Serotonin transporter 10270:Methoxytetrabenazine 10235:Dihydrotetrabenazine 10049:Arylcyclohexylamines 9344:Arylcyclohexylamines 8495:Dizocilpine (MK-801) 8449:Chaenomeles speciosa 8150:Benocyclidine (BTCP) 7821:Ion channel blockers 7333:Gabapentin enacarbil 6932:Hypericum perforatum 6800:Adjunctive therapies 5543:"Serotonin Syndrome" 4873:10.4088/jcp.v63n0107 4775:. 2008;4(3):281–285. 4692:10.1056/NEJMra041867 4227:. 69 Suppl E1: 4–7. 4162:Molecular Psychiatry 3363:(Suppl 3): S81–S86. 1909:visual snow syndrome 1897:visual snow syndrome 1887:Visual snow syndrome 1768:liver function tests 1352:monoamine hypothesis 1322:musculoskeletal pain 997:adrenergic receptors 889:tyrosine hydroxylase 871:autoreceptors. The α 862:adrenergic receptors 827:-histaminergic, and 771:mechanisms of action 570:appetite suppressant 9894:Threohydrobupropion 9759:Desmethylsertraline 9487:Desmethylcitalopram 9170:Threohydrobupropion 9035:Desmethylsertraline 8690:Threohydrobupropion 8465:Desmethylsertraline 5948:receptor modulators 5944:reuptake inhibitors 4740:10.2147/NDT.S141832 2721:European Psychiatry 2593:. 20 September 2021 2091:Special populations 2074:Comparison to SSRIs 1437: 1429:SNRIs at the human 1398:primary metabolites 965:blood–brain barrier 899:-activation of the 801:Mechanism of action 386:Diabetic neuropathy 319:Chemical structure 97:Menopausal symptoms 10134:dextropropoxyphene 8160:Dexmethylphenidate 7685:Never to phase III 6992:Never to phase III 4935:(Suppl 6): 33–37. 4598:Psychopharmacology 4565:10.1111/jcpt.12534 4524:. 23 December 2022 3416:10.7573/dic.212290 2996:Psychopharmacology 2842:on 11 October 2010 2651:. 16 November 2021 2016:Serotonin syndrome 1905: 1843:Serotonin Syndrome 1799:Sexual Dysfunction 1704:serotonin syndrome 1428: 1152: 1139: 1099: 1057:psychopharmacology 854: 798: 675:vasomotor symptoms 665: 609: 565: 523: 479: 414: 354: 291: 10387: 10386: 10382: 10168: 10167: 9443: 9418: 9417: 8863:Levophacetoperane 8733: 8708: 8707: 8570:Levophacetoperane 8145:4-Fluoropethidine 8080: 8019: 8018: 7927:Botulinum toxin A 7917:Alpha lipoic acid 7863:Local anesthetics 7736:pharmacotherapies 7695: 7694: 7267:Ethanol (alcohol) 7175:Ethyl loflazepate 7002: 7001: 6961: 6960: 6934:(St. John's Wort) 6885: 6884: 6850:lithium carbonate 6789: 6788: 6785: 6784: 6560: 6559: 6556: 6555: 6369:Amitriptylinoxide 6319: 6318: 6315: 6314: 5764:(10): 1205–1215. 5718:(4): 235–244.e2. 5453:10.1159/000491524 5417:10.1159/000491524 4803:10.1002/med.21476 4686:(11): 1112–1120. 3841:(11): 1217–1227. 3767:(21): 5395–5399. 3697:(11): 3328–3332. 3623:10.1021/jm8002262 3617:(13): 4038–4049. 3581:(24): 8455–8466. 3167:(20): 2463–2475. 3114:Neuropharmacology 2243:(19): 6890–6897. 1720:antiemetic agents 1694:Contraindications 1674:The half-life of 1667: 1666: 1624:0.55:1 (= 1:1.8) 1602:0.45:1 (= 1:2.2) 1424:Activity profiles 1414:monoamine oxidase 1369:neurotransmission 989:lateral tegmental 952: 916:negative feedback 779:phenylethylamines 720:monoamine oxidase 704:antimycobacterial 685: 684: 441:pain and chronic 228:neurotransmitters 180:anxiety disorders 167:) are a class of 149: 148: 104:Biological target 62:Class identifiers 16:(Redirected from 10429: 10404: 10403: 10402: 10395: 10349: 10336:Antagonist-like: 10230:Deutetrabenazine 10180: 10176: 10120:MIN-117 (WF-516) 10085:Dextromethorphan 9457:6-Nitroquipazine 9447: 9446: 9441: 9437: 9432: 9430: 9426: 8853:Hydroxybupropion 8737: 8736: 8731: 8727: 8722: 8720: 8716: 8610:MIN-117 (WF-516) 8550:Hydroxybupropion 8490:Diphenylpyraline 8221:Diphenylprolinol 8084: 8083: 8078: 8074: 8069: 8067: 8063: 8046: 8039: 8032: 8023: 8022: 8010: 8007:Sodium oxybate ( 7963:dextromethorphan 7884: 7880: 7803: 7799: 7777: 7773: 7758: 7754: 7729:Neuropathic pain 7722: 7715: 7708: 7699: 7698: 7531:Alpha-2 agonists 7521:Alpha-1 blockers 7514: 7442: 7438: 7427: 7423: 7412: 7408: 7397: 7393: 7382: 7378: 7367: 7363: 7321: 7315: 7312: 7140:Chlordiazepoxide 7107: 7103: 7099: 7095: 7059: 7055: 7029: 7022: 7015: 7006: 7005: 6942: 6908: 6891: 6890: 6864:triiodothyronine 6860:Thyroid hormones 6795: 6794: 6766: 6762: 6706: 6702: 6647:Phenoxypropazine 6579: 6578: 6566: 6565: 6510: 6506: 6352: 6348: 6342: 6341: 6325: 6324: 6204: 6200: 6171: 6167: 6138: 6134: 6105: 6101: 6072: 6068: 6024: 6020: 5966: 5962: 5956: 5955: 5938: 5937: 5918: 5911: 5904: 5895: 5894: 5888: 5887: 5877: 5845: 5839: 5838: 5828: 5796: 5790: 5789: 5752: 5746: 5745: 5735: 5703: 5694: 5693: 5683: 5651: 5642: 5641: 5631: 5607: 5601: 5600: 5598: 5596: 5590: 5579: 5571: 5565: 5564: 5562: 5561: 5538: 5532: 5531: 5521: 5489: 5483: 5482: 5464: 5436: 5430: 5429: 5419: 5395: 5389: 5388: 5378: 5346: 5340: 5339: 5310: 5304: 5303: 5301: 5299: 5288: 5282: 5281: 5271: 5239: 5233: 5232: 5222: 5190: 5184: 5183: 5173: 5141: 5132: 5131: 5095: 5089: 5088: 5086: 5085: 5071: 5065: 5064: 5054: 5030: 5021: 5020: 5018: 5017: 5003: 4997: 4996: 4986: 4954: 4945: 4944: 4924: 4918: 4917: 4915: 4891: 4885: 4884: 4855: 4849: 4848: 4846: 4845: 4831: 4825: 4824: 4814: 4797:(4): 1332–1403. 4782: 4776: 4769: 4763: 4762: 4752: 4742: 4718: 4712: 4711: 4675: 4666: 4665: 4663: 4661: 4638: 4632: 4631: 4621: 4589: 4578: 4577: 4567: 4543: 4534: 4533: 4531: 4529: 4514: 4499: 4498: 4496: 4494: 4489:. 29 August 2022 4479: 4464: 4463: 4461: 4459: 4444: 4431: 4430: 4394: 4388: 4387: 4380: 4374: 4373: 4336: 4327: 4326: 4316: 4284: 4278: 4277: 4267: 4243: 4237: 4236: 4220: 4214: 4213: 4195: 4177: 4168:(8): 3243–3256. 4153: 4147: 4146: 4144: 4143: 4129: 4123: 4122: 4112: 4080: 4074: 4073: 4037: 4031: 4030: 4020: 3996: 3990: 3989: 3972:(8): 1064–1071. 3957: 3951: 3950: 3940: 3908: 3902: 3901: 3884:(3–4): 351–359. 3873: 3867: 3866: 3829: 3820: 3819: 3802:(8): 2562–2566. 3791: 3785: 3784: 3756: 3750: 3749: 3732:(9): 2464–2467. 3721: 3715: 3714: 3686: 3675: 3674: 3657:(4): 1346–1349. 3646: 3635: 3634: 3605: 3599: 3598: 3569: 3558: 3557: 3528: 3515: 3514: 3496: 3487: 3486: 3476: 3444: 3438: 3437: 3427: 3404:Drugs in Context 3395: 3389: 3388: 3352: 3346: 3345: 3342:Human Physiology 3337: 3331: 3330: 3322: 3307: 3306: 3298: 3287: 3286: 3250: 3241: 3240: 3204: 3195: 3194: 3184: 3152: 3146: 3145: 3109: 3098: 3097: 3077: 3071: 3070: 3068: 3067: 3061: 3046: 3037: 3028: 3027: 2991: 2985: 2984: 2974: 2957:(7): 1058–1066. 2942: 2933: 2932: 2915:(8): 2138–2154. 2904: 2895: 2894: 2858: 2852: 2851: 2849: 2847: 2838:. Archived from 2825: 2819: 2818: 2801:(2–3): 119–128. 2790: 2784: 2783: 2781: 2779: 2768: 2753: 2752: 2716: 2707: 2706: 2670: 2661: 2660: 2658: 2656: 2641: 2635: 2634: 2632: 2630: 2624: 2617: 2609: 2603: 2602: 2600: 2598: 2583: 2554: 2553: 2536:(8): 1126–1143. 2525: 2512: 2511: 2474: 2468: 2467: 2443: 2434: 2433: 2397: 2388: 2387: 2377: 2366:10.1037/a0038550 2345: 2339: 2338: 2321:(7): 1206–1227. 2310: 2304: 2303: 2267: 2261: 2260: 2232: 2226: 2225: 2193: 2187: 2186: 2184: 2183: 2177:Cleveland Clinic 2168: 2118:younger adults. 2068:activated carbon 1776:anorexia nervosa 1712:anti-convulsants 1708:anti-depressants 1670:Pharmacokinetics 1662: 1658: 1648: 1644: 1640: 1580:0.06:1 (= 1:16) 1494: 1480: 1463: 1459: 1451: 1446: 1438: 1436: 1432: 1427: 1392:Pharmacodynamics 1373:neuropathic pain 1311:Neuropathic pain 1209:pharmacokinetics 1201:molecular weight 957:Active transport 950: 914:TCAs activate a 419:neuropathic pain 304: 303: 260:neuropathic pain 184:neuropathic pain 157: 133: 51: 30: 29: 21: 10437: 10436: 10432: 10431: 10430: 10428: 10427: 10426: 10412: 10411: 10410: 10400: 10398: 10390: 10388: 10383: 10343: 10321:DAT modulators: 10299: 10200:methamphetamine 10178: 10164: 10075:Cyclobenzaprine 10017:diphenhydramine 10005:brompheniramine 9979: 9908: 9707: 9673:Levomilnacipran 9631: 9439: 9431: 9428: 9414: 9312:brompheniramine 9296: 9260: 9184: 8983: 8944:Levomilnacipran 8907: 8878:Methylphenidate 8821: 8729: 8721: 8718: 8704: 8391: 8245: 8209: 8180:Methylphenidate 8155:Desoxypipradrol 8133: 8076: 8068: 8065: 8055: 8050: 8020: 8015: 7905: 7882: 7829:Anticonvulsants 7815: 7801: 7775: 7756: 7738: 7726: 7696: 7691: 7690: 7675:Clinical trials 7654: 7558: 7539:dexmedetomidine 7511:Antiadrenergics 7508: 7507: 7499: 7476: 7440: 7425: 7410: 7395: 7380: 7365: 7353:Antidepressants 7347: 7310: 7303: 7302: 7294: 7276: 7115:Benzodiazepines 7105: 7097: 7093: 7083: 7057: 7053: 7043: 7033: 7003: 6998: 6997: 6982:Clinical trials 6957: 6896: 6881: 6877: 6869: 6854:lithium citrate 6802: 6781: 6764: 6761: 6751: 6704: 6701: 6691: 6667:Tranylcypromine 6573: 6552: 6536: 6508: 6498: 6350: 6336: 6311: 6220: 6202: 6192: 6169: 6159: 6136: 6126: 6103: 6093: 6070: 6060: 6041:Levomilnacipran 6022: 6012: 5964: 5950: 5932: 5925:Antidepressants 5922: 5892: 5891: 5846: 5842: 5797: 5793: 5753: 5749: 5704: 5697: 5652: 5645: 5608: 5604: 5594: 5592: 5591:on 14 July 2011 5588: 5577: 5573: 5572: 5568: 5559: 5557: 5539: 5535: 5490: 5486: 5437: 5433: 5396: 5392: 5347: 5343: 5311: 5307: 5297: 5295: 5290: 5289: 5285: 5240: 5236: 5191: 5187: 5142: 5135: 5096: 5092: 5083: 5081: 5073: 5072: 5068: 5031: 5024: 5015: 5013: 5005: 5004: 5000: 4955: 4948: 4925: 4921: 4892: 4888: 4856: 4852: 4843: 4841: 4833: 4832: 4828: 4783: 4779: 4770: 4766: 4719: 4715: 4676: 4669: 4659: 4657: 4649: 4639: 4635: 4590: 4581: 4544: 4537: 4527: 4525: 4516: 4515: 4502: 4492: 4490: 4481: 4480: 4467: 4457: 4455: 4454:. 25 March 2022 4446: 4445: 4434: 4395: 4391: 4382: 4381: 4377: 4337: 4330: 4285: 4281: 4244: 4240: 4221: 4217: 4154: 4150: 4141: 4139: 4131: 4130: 4126: 4081: 4077: 4048:(10): 954–961. 4038: 4034: 3997: 3993: 3958: 3954: 3909: 3905: 3874: 3870: 3830: 3823: 3792: 3788: 3757: 3753: 3722: 3718: 3687: 3678: 3647: 3638: 3606: 3602: 3570: 3561: 3529: 3518: 3511: 3497: 3490: 3445: 3441: 3396: 3392: 3353: 3349: 3338: 3334: 3323: 3310: 3299: 3290: 3251: 3244: 3205: 3198: 3153: 3149: 3110: 3101: 3078: 3074: 3065: 3063: 3059: 3044: 3038: 3031: 2992: 2988: 2943: 2936: 2905: 2898: 2859: 2855: 2845: 2843: 2826: 2822: 2791: 2787: 2777: 2775: 2770: 2769: 2756: 2717: 2710: 2671: 2664: 2654: 2652: 2643: 2642: 2638: 2628: 2626: 2625:on 26 June 2016 2622: 2615: 2611: 2610: 2606: 2596: 2594: 2585: 2584: 2557: 2526: 2515: 2475: 2471: 2444: 2437: 2398: 2391: 2346: 2342: 2311: 2307: 2268: 2264: 2233: 2229: 2194: 2190: 2181: 2179: 2169: 2165: 2160: 2133: 2124: 2115: 2106: 2098: 2093: 2076: 2059: 1998: 1990: 1985: 1951: 1942: 1937: 1889: 1883: 1881:Visual problems 1854: 1845: 1835:(Levitra), and 1801: 1792: 1740:St. John's wort 1696: 1672: 1655:values for the 1654: 1650: 1636: 1632: 1608:Levomilnacipran 1493: 1486: 1479: 1472: 1455: 1426: 1394: 1344: 1335: 1330: 1270: 1261: 1252: 1247: 1245:Clinical trials 1229: 1221:cytochrome P450 1213:bioavailability 1177:racemic mixture 1173:stereochemistry 1144: 1104: 1070: 1065: 1038: 1029: 1024:adrenergic, or 1022: 1015: 999:, as discussed 996: 985:locus coeruleus 981: 945: 937:cerebral cortex 931: 925:desensitization 923:receptors. The 922: 906: 897:phosphorylation 874: 870: 846: 829:sodium channels 826: 822: 818: 807:pathophysiology 803: 696: 690: 499: 497: 477:Levomilnacipran 455:Levomilnacipran 313:FDA Indications 299:levomilnacipran 283: 158: 151: 129: 57: 28: 23: 22: 15: 12: 11: 5: 10435: 10425: 10424: 10409: 10408: 10385: 10384: 10348: 10345: 10344: 10342: 10341: 10329: 10317: 10316: 10311:DAT enhancers: 10307: 10305: 10301: 10300: 10298: 10297: 10292: 10287: 10282: 10277: 10272: 10267: 10262: 10257: 10252: 10247: 10242: 10237: 10232: 10227: 10222: 10217: 10212: 10207: 10189: 10183: 10181: 10170: 10169: 10166: 10165: 10163: 10162: 10157: 10127: 10122: 10117: 10112: 10107: 10102: 10097: 10092: 10087: 10082: 10077: 10072: 10046: 10035:Antipsychotics 10032: 10029:tripelennamine 10013:dimenhydrinate 10009:chlorphenamine 10001:Antihistamines 9998: 9993: 9984: 9981: 9980: 9978: 9977: 9972: 9967: 9962: 9957: 9952: 9947: 9942: 9937: 9935:Cyanodothiepin 9932: 9927: 9922: 9913: 9910: 9909: 9907: 9906: 9896: 9891: 9886: 9881: 9876: 9871: 9866: 9861: 9856: 9851: 9846: 9841: 9836: 9831: 9826: 9821: 9816: 9811: 9806: 9801: 9796: 9791: 9786: 9781: 9776: 9771: 9766: 9761: 9756: 9751: 9746: 9741: 9736: 9731: 9726: 9721: 9712: 9709: 9708: 9706: 9705: 9700: 9695: 9690: 9685: 9680: 9675: 9670: 9665: 9660: 9658:Desvenlafaxine 9655: 9650: 9645: 9636: 9633: 9632: 9630: 9629: 9624: 9619: 9614: 9609: 9604: 9599: 9594: 9589: 9584: 9575: 9574: 9569: 9564: 9559: 9554: 9549: 9544: 9539: 9534: 9529: 9524: 9519: 9514: 9509: 9504: 9499: 9494: 9489: 9484: 9479: 9474: 9469: 9464: 9459: 9450: 9444: 9420: 9419: 9416: 9415: 9413: 9412: 9382: 9377: 9372: 9365: 9360: 9355: 9341: 9330:Antipsychotics 9327: 9324:tripelennamine 9316:chlorphenamine 9308:Antihistamines 9301: 9298: 9297: 9295: 9294: 9289: 9284: 9279: 9274: 9265: 9262: 9261: 9259: 9258: 9253: 9248: 9243: 9238: 9233: 9228: 9223: 9218: 9213: 9208: 9203: 9198: 9189: 9186: 9185: 9183: 9182: 9172: 9167: 9162: 9157: 9152: 9147: 9142: 9137: 9132: 9127: 9122: 9117: 9112: 9107: 9102: 9097: 9092: 9087: 9082: 9077: 9072: 9067: 9062: 9057: 9052: 9047: 9042: 9037: 9032: 9027: 9022: 9017: 9012: 9007: 9002: 8997: 8988: 8985: 8984: 8982: 8981: 8976: 8971: 8966: 8961: 8956: 8951: 8946: 8941: 8936: 8931: 8929:Desvenlafaxine 8926: 8921: 8912: 8909: 8908: 8906: 8905: 8900: 8895: 8890: 8885: 8880: 8875: 8870: 8865: 8860: 8855: 8850: 8845: 8840: 8835: 8826: 8823: 8822: 8820: 8819: 8814: 8809: 8804: 8799: 8794: 8789: 8784: 8779: 8774: 8769: 8764: 8759: 8754: 8749: 8740: 8734: 8710: 8709: 8706: 8705: 8703: 8702: 8697: 8695:Tripelennamine 8692: 8687: 8682: 8677: 8672: 8667: 8662: 8657: 8652: 8647: 8642: 8637: 8632: 8627: 8622: 8617: 8612: 8607: 8602: 8597: 8592: 8587: 8582: 8577: 8572: 8567: 8562: 8557: 8552: 8547: 8542: 8537: 8532: 8527: 8522: 8517: 8512: 8507: 8502: 8497: 8492: 8487: 8482: 8477: 8472: 8467: 8462: 8457: 8452: 8445: 8440: 8435: 8430: 8425: 8420: 8418:Amfonelic acid 8415: 8410: 8405: 8396: 8393: 8392: 8390: 8389: 8384: 8379: 8374: 8369: 8364: 8359: 8354: 8349: 8344: 8339: 8334: 8329: 8324: 8319: 8314: 8309: 8304: 8299: 8294: 8289: 8284: 8279: 8274: 8269: 8264: 8259: 8250: 8247: 8246: 8244: 8243: 8238: 8233: 8228: 8223: 8214: 8211: 8210: 8208: 8207: 8202: 8197: 8192: 8187: 8182: 8177: 8172: 8170:Ethylphenidate 8167: 8162: 8157: 8152: 8147: 8138: 8135: 8134: 8132: 8131: 8126: 8121: 8116: 8111: 8106: 8101: 8096: 8087: 8081: 8057: 8056: 8049: 8048: 8041: 8034: 8026: 8017: 8016: 8014: 8013: 8004: 7970: 7952: 7934: 7929: 7924: 7919: 7913: 7911: 7907: 7906: 7904: 7903: 7898: 7875: 7870: 7860: 7825: 7823: 7817: 7816: 7814: 7813: 7791: 7768: 7748: 7746: 7744:Monoaminergics 7740: 7739: 7725: 7724: 7717: 7710: 7702: 7693: 7692: 7689: 7688: 7687: 7686: 7683: 7672: 7666: 7660: 7659: 7656: 7655: 7653: 7652: 7647: 7642: 7637: 7632: 7627: 7622: 7617: 7612: 7607: 7602: 7597: 7592: 7587: 7582: 7577: 7572: 7566: 7564: 7560: 7559: 7557: 7556: 7546: 7528: 7517: 7515: 7505:Sympatholytics 7501: 7500: 7498: 7497: 7492: 7486: 7484: 7482:Antipsychotics 7478: 7477: 7475: 7474: 7469: 7464: 7459: 7454: 7433: 7418: 7403: 7388: 7373: 7357: 7355: 7349: 7348: 7346: 7345: 7340: 7335: 7330: 7324: 7322: 7308: 7300:Gabapentinoids 7296: 7295: 7293: 7292: 7286: 7284: 7278: 7277: 7275: 7274: 7269: 7264: 7259: 7254: 7244: 7234: 7222: 7217: 7212: 7207: 7202: 7197: 7192: 7187: 7182: 7177: 7172: 7167: 7162: 7157: 7152: 7147: 7142: 7137: 7132: 7127: 7122: 7110: 7108: 7091: 7085: 7084: 7082: 7081: 7076: 7071: 7065: 7063: 7051: 7045: 7044: 7032: 7031: 7024: 7017: 7009: 7000: 6999: 6996: 6995: 6994: 6993: 6990: 6979: 6973: 6967: 6966: 6963: 6962: 6959: 6958: 6956: 6955: 6950: 6945: 6936: 6928: 6911: 6905:Ademetionine ( 6901: 6898: 6897: 6887: 6886: 6883: 6882: 6880: 6879: 6875: 6867: 6857: 6843: 6838: 6807: 6804: 6803: 6791: 6790: 6787: 6786: 6783: 6782: 6780: 6779: 6770: 6768: 6759: 6753: 6752: 6750: 6749: 6744: 6739: 6734: 6729: 6724: 6719: 6710: 6708: 6699: 6693: 6692: 6690: 6689: 6680: 6679: 6670: 6669: 6664: 6659: 6654: 6649: 6644: 6639: 6634: 6629: 6624: 6619: 6614: 6609: 6604: 6599: 6594: 6585: 6583: 6575: 6574: 6562: 6561: 6558: 6557: 6554: 6553: 6551: 6550: 6544: 6542: 6538: 6537: 6535: 6534: 6529: 6524: 6519: 6513: 6511: 6500: 6499: 6497: 6496: 6491: 6486: 6481: 6476: 6471: 6466: 6461: 6456: 6451: 6446: 6441: 6436: 6431: 6426: 6424:Imipraminoxide 6421: 6416: 6411: 6406: 6401: 6396: 6391: 6386: 6381: 6376: 6371: 6366: 6361: 6355: 6353: 6338: 6337: 6321: 6320: 6317: 6316: 6313: 6312: 6310: 6309: 6304: 6299: 6294: 6289: 6284: 6279: 6274: 6269: 6264: 6259: 6254: 6249: 6244: 6239: 6234: 6228: 6226: 6222: 6221: 6219: 6218: 6213: 6207: 6205: 6194: 6193: 6191: 6190: 6185: 6180: 6174: 6172: 6161: 6160: 6158: 6157: 6152: 6147: 6141: 6139: 6128: 6127: 6125: 6124: 6119: 6114: 6108: 6106: 6095: 6094: 6092: 6091: 6086: 6081: 6075: 6073: 6062: 6061: 6059: 6058: 6053: 6048: 6043: 6038: 6033: 6031:Desvenlafaxine 6027: 6025: 6014: 6013: 6011: 6010: 6005: 6000: 5995: 5990: 5985: 5980: 5975: 5969: 5967: 5952: 5951: 5934: 5933: 5921: 5920: 5913: 5906: 5898: 5890: 5889: 5840: 5811:(3): 517–534. 5791: 5747: 5695: 5643: 5622:(4): 702–710. 5602: 5566: 5533: 5504:(3): 151–161. 5484: 5447:(4): 195–203. 5431: 5410:(4): 195–203. 5390: 5361:(6): 357–368. 5341: 5305: 5283: 5234: 5185: 5156:(4): 433–438. 5133: 5106:(3): 330–332. 5090: 5066: 5045:(7): 988–992. 5022: 5011:www.mdedge.com 4998: 4969:(4): 191–196. 4946: 4919: 4906:(3): 156–166. 4886: 4850: 4826: 4777: 4764: 4713: 4667: 4647: 4633: 4579: 4558:(4): 513–517. 4535: 4500: 4465: 4432: 4405:(6): 849–858. 4389: 4375: 4348:(3): 469–479. 4328: 4279: 4258:(6): 399–409. 4238: 4215: 4148: 4124: 4075: 4032: 3991: 3952: 3923:(4): 331–336. 3903: 3868: 3821: 3786: 3751: 3716: 3676: 3636: 3600: 3559: 3540:(3): 699–703. 3516: 3509: 3488: 3439: 3390: 3347: 3332: 3308: 3288: 3261:(9): 732–747. 3242: 3215:(5): 461–475. 3196: 3147: 3120:(6): 815–823. 3099: 3088:(9): 609–630. 3072: 3029: 2986: 2934: 2896: 2869:(2): 223–230. 2853: 2820: 2785: 2754: 2708: 2681:(7): 581–609. 2662: 2636: 2604: 2555: 2513: 2486:(2): 576–584. 2469: 2435: 2408:(2): 657–665. 2389: 2340: 2305: 2262: 2227: 2208:(9): 732–747. 2188: 2162: 2161: 2159: 2156: 2155: 2154: 2149: 2144: 2139: 2132: 2129: 2123: 2120: 2114: 2111: 2105: 2102: 2097: 2094: 2092: 2089: 2075: 2072: 2063:cyproheptadine 2058: 2055: 2054: 2053: 2048: 2043: 2038: 2033: 2028: 2023: 2018: 2013: 2008: 1997: 1994: 1989: 1986: 1984: 1981: 1950: 1947: 1941: 1938: 1936: 1933: 1885:Main article: 1882: 1879: 1859:anticoagulants 1853: 1850: 1844: 1841: 1821:PDE5 Inhibitor 1800: 1797: 1791: 1788: 1759:norepinephrine 1728:methylene blue 1695: 1692: 1680:desvenlafaxine 1671: 1668: 1665: 1664: 1652: 1634: 1630: 1626: 1625: 1622: 1619: 1616: 1613: 1610: 1604: 1603: 1600: 1597: 1594: 1591: 1588: 1582: 1581: 1578: 1576: 1573: 1571: 1568: 1562: 1561: 1558: 1555: 1552: 1549: 1546: 1540: 1539: 1536: 1533: 1530: 1527: 1524: 1522:Desvenlafaxine 1518: 1517: 1514: 1511: 1508: 1505: 1502: 1496: 1495: 1491: 1487: 1484: 1481: 1477: 1473: 1470: 1466: 1465: 1452: 1447: 1442: 1425: 1422: 1410:frontal cortex 1393: 1390: 1348:norepinephrine 1343: 1342:Mode of action 1340: 1334: 1331: 1329: 1326: 1325: 1324: 1318: 1313: 1308: 1306:Panic disorder 1303: 1298: 1292: 1286: 1280: 1269: 1266: 1260: 1257: 1251: 1248: 1246: 1243: 1228: 1225: 1143: 1140: 1111:desvenlafaxine 1103: 1100: 1069: 1066: 1064: 1061: 1037: 1034: 1027: 1020: 1013: 994: 980: 977: 944: 941: 929: 920: 904: 872: 868: 845: 842: 837:cardiotoxicity 833:cardiac muscle 824: 823:-adrenergic, H 820: 816: 802: 799: 689: 686: 683: 682: 666: 657: 654: 653: 652: 649: 646: 645:Panic disorder 643: 640: 637: 632: 629: 623: 622: 610: 601: 598: 597: 596: 591: 588: 582: 581: 566: 557: 554: 553: 552: 545: 542: 536: 535: 524: 514: 511: 510: 509: 506: 501: 494: 488: 487: 480: 470: 467: 466: 465: 460: 457: 451: 450: 439:osteoarthritis 415: 405: 402: 401: 400: 395: 388: 383: 380: 377: 372: 366: 360: 359: 355: 346: 343: 342: 341: 336: 334:Khedezla (ER) 330: 328:Desvenlafaxine 324: 323: 320: 317: 314: 311: 308: 282: 279: 255:synaptic cleft 224:norepinephrine 174:used to treat 169:antidepressant 147: 146: 140: 139: 135: 134: 127: 121: 120: 119:External links 116: 115: 106: 100: 99: 78: 74: 73: 70: 64: 63: 59: 58: 52: 44: 43: 35: 34: 26: 9: 6: 4: 3: 2: 10434: 10423: 10420: 10419: 10417: 10407: 10397: 10396: 10393: 10381: 10380: 10376: 10372: 10371:Serotonergics 10368: 10367:Dopaminergics 10364: 10360: 10356: 10353: 10346: 10340: 10337: 10333: 10330: 10328: 10325: 10324:Agonist-like: 10322: 10319: 10318: 10315: 10312: 10309: 10308: 10306: 10302: 10296: 10293: 10291: 10288: 10286: 10285:Tetrabenazine 10283: 10281: 10278: 10276: 10273: 10271: 10268: 10266: 10263: 10261: 10258: 10256: 10253: 10251: 10248: 10246: 10243: 10241: 10238: 10236: 10233: 10231: 10228: 10226: 10223: 10221: 10218: 10216: 10213: 10211: 10208: 10205: 10201: 10197: 10193: 10190: 10188: 10185: 10184: 10182: 10177: 10171: 10161: 10158: 10155: 10151: 10147: 10143: 10139: 10135: 10131: 10128: 10126: 10123: 10121: 10118: 10116: 10113: 10111: 10108: 10106: 10103: 10101: 10098: 10096: 10093: 10091: 10088: 10086: 10083: 10081: 10078: 10076: 10073: 10070: 10069:phencyclidine 10066: 10065:methoxetamine 10062: 10058: 10054: 10050: 10047: 10044: 10040: 10036: 10033: 10030: 10026: 10022: 10018: 10014: 10010: 10006: 10002: 9999: 9997: 9994: 9992: 9989: 9986: 9985: 9982: 9976: 9975:Protriptyline 9973: 9971: 9968: 9966: 9965:Nortriptyline 9963: 9961: 9958: 9956: 9953: 9951: 9948: 9946: 9943: 9941: 9938: 9936: 9933: 9931: 9928: 9926: 9923: 9921: 9920:Amitriptyline 9918: 9915: 9914: 9911: 9904: 9900: 9897: 9895: 9892: 9890: 9887: 9885: 9884:Tedatioxetine 9882: 9880: 9877: 9875: 9872: 9870: 9867: 9865: 9862: 9860: 9857: 9855: 9852: 9850: 9847: 9845: 9842: 9840: 9837: 9835: 9832: 9830: 9827: 9825: 9822: 9820: 9817: 9815: 9812: 9810: 9807: 9805: 9802: 9800: 9797: 9795: 9792: 9790: 9787: 9785: 9782: 9780: 9777: 9775: 9772: 9770: 9767: 9765: 9762: 9760: 9757: 9755: 9752: 9750: 9747: 9745: 9744:Centanafadine 9742: 9740: 9737: 9735: 9732: 9730: 9727: 9725: 9722: 9720: 9717: 9714: 9713: 9710: 9704: 9701: 9699: 9696: 9694: 9691: 9689: 9688:N-Methyl-PPPA 9686: 9684: 9681: 9679: 9676: 9674: 9671: 9669: 9666: 9664: 9661: 9659: 9656: 9654: 9651: 9649: 9646: 9644: 9641: 9638: 9637: 9634: 9628: 9625: 9623: 9620: 9618: 9615: 9613: 9610: 9608: 9605: 9603: 9600: 9598: 9595: 9593: 9590: 9588: 9585: 9583: 9580: 9577: 9576: 9573: 9570: 9568: 9565: 9563: 9560: 9558: 9555: 9553: 9550: 9548: 9545: 9543: 9540: 9538: 9535: 9533: 9530: 9528: 9527:Norfluoxetine 9525: 9523: 9520: 9518: 9515: 9513: 9510: 9508: 9505: 9503: 9500: 9498: 9495: 9493: 9490: 9488: 9485: 9483: 9480: 9478: 9475: 9473: 9470: 9468: 9467:Centpropazine 9465: 9463: 9460: 9458: 9455: 9452: 9451: 9448: 9445: 9438: 9427: 9421: 9410: 9406: 9402: 9398: 9394: 9390: 9389:desmetramadol 9386: 9383: 9381: 9378: 9376: 9373: 9371: 9370: 9369:Ginkgo biloba 9366: 9364: 9361: 9359: 9356: 9353: 9352:phencyclidine 9349: 9345: 9342: 9339: 9335: 9331: 9328: 9325: 9321: 9317: 9313: 9309: 9306: 9303: 9302: 9299: 9293: 9290: 9288: 9285: 9283: 9280: 9278: 9275: 9273: 9270: 9267: 9266: 9263: 9257: 9254: 9252: 9251:Protriptyline 9249: 9247: 9246:Nortriptyline 9244: 9242: 9239: 9237: 9234: 9232: 9229: 9227: 9224: 9222: 9219: 9217: 9214: 9212: 9209: 9207: 9204: 9202: 9199: 9197: 9196:Amitriptyline 9194: 9191: 9190: 9187: 9180: 9176: 9173: 9171: 9168: 9166: 9163: 9161: 9160:Tedatioxetine 9158: 9156: 9153: 9151: 9148: 9146: 9143: 9141: 9138: 9136: 9133: 9131: 9128: 9126: 9123: 9121: 9118: 9116: 9113: 9111: 9108: 9106: 9103: 9101: 9098: 9096: 9093: 9091: 9088: 9086: 9083: 9081: 9078: 9076: 9073: 9071: 9068: 9066: 9063: 9061: 9058: 9056: 9053: 9051: 9048: 9046: 9043: 9041: 9038: 9036: 9033: 9031: 9028: 9026: 9023: 9021: 9020:Centanafadine 9018: 9016: 9013: 9011: 9008: 9006: 9003: 9001: 8998: 8996: 8993: 8990: 8989: 8986: 8980: 8977: 8975: 8972: 8970: 8967: 8965: 8962: 8960: 8959:N-Methyl-PPPA 8957: 8955: 8952: 8950: 8947: 8945: 8942: 8940: 8937: 8935: 8932: 8930: 8927: 8925: 8922: 8920: 8917: 8914: 8913: 8910: 8904: 8901: 8899: 8896: 8894: 8891: 8889: 8886: 8884: 8881: 8879: 8876: 8874: 8871: 8869: 8866: 8864: 8861: 8859: 8856: 8854: 8851: 8849: 8846: 8844: 8841: 8839: 8836: 8834: 8831: 8828: 8827: 8824: 8818: 8815: 8813: 8810: 8808: 8805: 8803: 8800: 8798: 8795: 8793: 8790: 8788: 8785: 8783: 8780: 8778: 8775: 8773: 8770: 8768: 8765: 8763: 8760: 8758: 8755: 8753: 8750: 8748: 8745: 8742: 8741: 8738: 8735: 8728: 8717: 8711: 8701: 8698: 8696: 8693: 8691: 8688: 8686: 8685:Tedatioxetine 8683: 8681: 8678: 8676: 8673: 8671: 8668: 8666: 8663: 8661: 8658: 8656: 8653: 8651: 8648: 8646: 8643: 8641: 8638: 8636: 8633: 8631: 8628: 8626: 8623: 8621: 8618: 8616: 8613: 8611: 8608: 8606: 8603: 8601: 8598: 8596: 8593: 8591: 8588: 8586: 8583: 8581: 8578: 8576: 8573: 8571: 8568: 8566: 8563: 8561: 8558: 8556: 8553: 8551: 8548: 8546: 8543: 8541: 8538: 8536: 8533: 8531: 8528: 8526: 8523: 8521: 8518: 8516: 8513: 8511: 8508: 8506: 8503: 8501: 8498: 8496: 8493: 8491: 8488: 8486: 8483: 8481: 8478: 8476: 8473: 8471: 8468: 8466: 8463: 8461: 8458: 8456: 8453: 8451: 8450: 8446: 8444: 8441: 8439: 8436: 8434: 8431: 8429: 8426: 8424: 8421: 8419: 8416: 8414: 8411: 8409: 8406: 8404: 8401: 8398: 8397: 8394: 8388: 8385: 8383: 8380: 8378: 8375: 8373: 8370: 8368: 8365: 8363: 8360: 8358: 8355: 8353: 8350: 8348: 8345: 8343: 8340: 8338: 8335: 8333: 8330: 8328: 8325: 8323: 8320: 8318: 8315: 8313: 8310: 8308: 8307:Ioflupane (I) 8305: 8303: 8300: 8298: 8295: 8293: 8290: 8288: 8285: 8283: 8280: 8278: 8275: 8273: 8270: 8268: 8265: 8263: 8260: 8258: 8255: 8252: 8251: 8248: 8242: 8239: 8237: 8234: 8232: 8229: 8227: 8224: 8222: 8219: 8218:Pyrrolidines: 8216: 8215: 8212: 8206: 8205:Tenocyclidine 8203: 8201: 8198: 8196: 8193: 8191: 8190:Phencyclidine 8188: 8186: 8183: 8181: 8178: 8176: 8173: 8171: 8168: 8166: 8163: 8161: 8158: 8156: 8153: 8151: 8148: 8146: 8143: 8140: 8139: 8136: 8130: 8127: 8125: 8122: 8120: 8117: 8115: 8112: 8110: 8107: 8105: 8102: 8100: 8097: 8095: 8092: 8089: 8088: 8085: 8082: 8075: 8064: 8058: 8054: 8047: 8042: 8040: 8035: 8033: 8028: 8027: 8024: 8012: 8005: 8002: 7998: 7994: 7993:buprenorphine 7990: 7986: 7982: 7978: 7974: 7971: 7968: 7964: 7960: 7956: 7953: 7950: 7946: 7942: 7938: 7935: 7933: 7930: 7928: 7925: 7923: 7920: 7918: 7915: 7914: 7912: 7908: 7902: 7899: 7896: 7892: 7891:nortriptyline 7888: 7887:amitriptyline 7881: 7876: 7874: 7871: 7868: 7864: 7861: 7858: 7854: 7850: 7849:oxcarbazepine 7846: 7845:carbamazepine 7842: 7838: 7834: 7830: 7827: 7826: 7824: 7822: 7818: 7811: 7807: 7800: 7795: 7792: 7789: 7785: 7784:nortriptyline 7781: 7780:amitriptyline 7774: 7769: 7766: 7762: 7755: 7750: 7749: 7747: 7745: 7741: 7737: 7734: 7730: 7723: 7718: 7716: 7711: 7709: 7704: 7703: 7700: 7684: 7682: 7679: 7678: 7676: 7673: 7670: 7667: 7665: 7662: 7661: 7657: 7651: 7648: 7646: 7643: 7641: 7638: 7636: 7633: 7631: 7628: 7626: 7623: 7621: 7620:Phenaglycodol 7618: 7616: 7613: 7611: 7608: 7606: 7603: 7601: 7598: 7596: 7593: 7591: 7588: 7586: 7583: 7581: 7578: 7576: 7573: 7571: 7568: 7567: 7565: 7561: 7554: 7550: 7549:Beta blockers 7547: 7544: 7540: 7536: 7532: 7529: 7526: 7522: 7519: 7518: 7516: 7512: 7506: 7502: 7496: 7493: 7491: 7488: 7487: 7485: 7483: 7479: 7473: 7470: 7468: 7465: 7463: 7460: 7458: 7455: 7453: 7450: 7446: 7439: 7434: 7431: 7424: 7419: 7416: 7409: 7404: 7401: 7394: 7389: 7386: 7379: 7374: 7371: 7364: 7359: 7358: 7356: 7354: 7350: 7344: 7341: 7339: 7336: 7334: 7331: 7329: 7326: 7325: 7323: 7319: 7316: 7301: 7297: 7291: 7288: 7287: 7285: 7283: 7279: 7273: 7270: 7268: 7265: 7263: 7262:Chlormezanone 7260: 7258: 7255: 7252: 7248: 7245: 7242: 7241:phenobarbital 7238: 7235: 7233: 7230: 7226: 7223: 7221: 7218: 7216: 7213: 7211: 7208: 7206: 7203: 7201: 7198: 7196: 7193: 7191: 7188: 7186: 7183: 7181: 7178: 7176: 7173: 7171: 7168: 7166: 7163: 7161: 7158: 7156: 7153: 7151: 7148: 7146: 7143: 7141: 7138: 7136: 7133: 7131: 7128: 7126: 7123: 7121: 7118: 7116: 7112: 7111: 7109: 7104: 7096: 7086: 7080: 7077: 7075: 7072: 7070: 7067: 7066: 7064: 7062: 7056: 7046: 7041: 7037: 7030: 7025: 7023: 7018: 7016: 7011: 7010: 7007: 6991: 6989: 6986: 6985: 6983: 6980: 6977: 6974: 6972: 6969: 6968: 6964: 6954: 6951: 6949: 6946: 6944: 6937: 6935: 6933: 6929: 6926: 6922: 6918: 6917:neurosteroids 6915: 6912: 6910: 6903: 6902: 6899: 6895:Miscellaneous 6892: 6888: 6873: 6872:levothyroxine 6865: 6861: 6858: 6855: 6851: 6847: 6844: 6842: 6839: 6836: 6832: 6828: 6824: 6820: 6819:brexpiprazole 6816: 6812: 6809: 6808: 6805: 6801: 6796: 6792: 6778: 6775: 6774:Irreversible: 6772: 6771: 6769: 6763: 6754: 6748: 6745: 6743: 6740: 6738: 6735: 6733: 6730: 6728: 6725: 6723: 6720: 6718: 6715: 6712: 6711: 6709: 6703: 6694: 6688: 6685: 6682: 6681: 6678: 6675: 6672: 6671: 6668: 6665: 6663: 6660: 6658: 6655: 6653: 6650: 6648: 6645: 6643: 6640: 6638: 6635: 6633: 6630: 6628: 6625: 6623: 6620: 6618: 6615: 6613: 6610: 6608: 6607:Isocarboxazid 6605: 6603: 6600: 6598: 6595: 6593: 6590: 6589:Irreversible: 6587: 6586: 6584: 6582:Non-selective 6580: 6576: 6572: 6567: 6563: 6549: 6546: 6545: 6543: 6539: 6533: 6530: 6528: 6525: 6523: 6520: 6518: 6515: 6514: 6512: 6507: 6501: 6495: 6492: 6490: 6487: 6485: 6482: 6480: 6479:Protriptyline 6477: 6475: 6472: 6470: 6467: 6465: 6462: 6460: 6457: 6455: 6454:Nortriptyline 6452: 6450: 6449:Nitroxazepine 6447: 6445: 6442: 6440: 6437: 6435: 6432: 6430: 6427: 6425: 6422: 6420: 6417: 6415: 6412: 6410: 6407: 6405: 6402: 6400: 6397: 6395: 6392: 6390: 6389:Demexiptiline 6387: 6385: 6382: 6380: 6377: 6375: 6372: 6370: 6367: 6365: 6364:Amitriptyline 6362: 6360: 6357: 6356: 6354: 6349: 6343: 6339: 6335: 6331: 6326: 6322: 6308: 6305: 6303: 6300: 6298: 6295: 6293: 6290: 6288: 6285: 6283: 6280: 6278: 6275: 6273: 6270: 6268: 6265: 6263: 6260: 6258: 6255: 6253: 6250: 6248: 6245: 6243: 6240: 6238: 6235: 6233: 6230: 6229: 6227: 6223: 6217: 6214: 6212: 6209: 6208: 6206: 6201: 6195: 6189: 6186: 6184: 6181: 6179: 6176: 6175: 6173: 6168: 6162: 6156: 6153: 6151: 6148: 6146: 6143: 6142: 6140: 6135: 6129: 6123: 6120: 6118: 6115: 6113: 6110: 6109: 6107: 6102: 6096: 6090: 6087: 6085: 6082: 6080: 6077: 6076: 6074: 6069: 6063: 6057: 6054: 6052: 6049: 6047: 6044: 6042: 6039: 6037: 6034: 6032: 6029: 6028: 6026: 6021: 6015: 6009: 6006: 6004: 6001: 5999: 5996: 5994: 5991: 5989: 5986: 5984: 5981: 5979: 5976: 5974: 5971: 5970: 5968: 5963: 5957: 5953: 5949: 5945: 5939: 5935: 5930: 5926: 5919: 5914: 5912: 5907: 5905: 5900: 5899: 5896: 5885: 5881: 5876: 5871: 5867: 5863: 5859: 5855: 5851: 5844: 5836: 5832: 5827: 5822: 5818: 5814: 5810: 5806: 5802: 5795: 5787: 5783: 5779: 5775: 5771: 5767: 5763: 5759: 5751: 5743: 5739: 5734: 5729: 5725: 5721: 5717: 5713: 5709: 5702: 5700: 5691: 5687: 5682: 5677: 5673: 5669: 5665: 5661: 5657: 5650: 5648: 5639: 5635: 5630: 5625: 5621: 5617: 5613: 5606: 5587: 5583: 5576: 5570: 5556: 5552: 5548: 5544: 5537: 5529: 5525: 5520: 5515: 5511: 5507: 5503: 5499: 5495: 5488: 5480: 5476: 5472: 5468: 5463: 5458: 5454: 5450: 5446: 5442: 5435: 5427: 5423: 5418: 5413: 5409: 5405: 5401: 5394: 5386: 5382: 5377: 5372: 5368: 5364: 5360: 5356: 5352: 5345: 5337: 5333: 5329: 5325: 5321: 5317: 5309: 5293: 5287: 5279: 5275: 5270: 5265: 5261: 5257: 5253: 5249: 5245: 5238: 5230: 5226: 5221: 5216: 5212: 5208: 5205:(46): e2022. 5204: 5200: 5196: 5189: 5181: 5177: 5172: 5167: 5163: 5159: 5155: 5151: 5147: 5140: 5138: 5129: 5125: 5121: 5117: 5113: 5109: 5105: 5101: 5094: 5080: 5076: 5070: 5062: 5058: 5053: 5048: 5044: 5040: 5036: 5029: 5027: 5012: 5008: 5002: 4994: 4990: 4985: 4980: 4976: 4972: 4968: 4964: 4960: 4953: 4951: 4942: 4938: 4934: 4930: 4923: 4914: 4909: 4905: 4901: 4897: 4890: 4882: 4878: 4874: 4870: 4866: 4862: 4854: 4840: 4836: 4830: 4822: 4818: 4813: 4808: 4804: 4800: 4796: 4792: 4788: 4781: 4774: 4768: 4760: 4756: 4751: 4746: 4741: 4736: 4733:: 2781–2796. 4732: 4728: 4724: 4717: 4709: 4705: 4701: 4697: 4693: 4689: 4685: 4681: 4674: 4672: 4655: 4651: 4643: 4637: 4629: 4625: 4620: 4615: 4611: 4607: 4603: 4599: 4595: 4588: 4586: 4584: 4575: 4571: 4566: 4561: 4557: 4553: 4549: 4542: 4540: 4523: 4519: 4513: 4511: 4509: 4507: 4505: 4488: 4484: 4478: 4476: 4474: 4472: 4470: 4453: 4449: 4443: 4441: 4439: 4437: 4428: 4424: 4420: 4416: 4412: 4408: 4404: 4400: 4393: 4385: 4379: 4371: 4367: 4363: 4359: 4355: 4351: 4347: 4343: 4335: 4333: 4324: 4320: 4315: 4310: 4306: 4302: 4298: 4294: 4290: 4283: 4275: 4271: 4266: 4261: 4257: 4253: 4249: 4242: 4234: 4230: 4226: 4219: 4211: 4207: 4203: 4199: 4194: 4189: 4185: 4181: 4176: 4171: 4167: 4163: 4159: 4152: 4138: 4134: 4128: 4120: 4116: 4111: 4106: 4102: 4098: 4094: 4090: 4086: 4079: 4071: 4067: 4063: 4059: 4055: 4051: 4047: 4043: 4036: 4028: 4024: 4019: 4014: 4010: 4006: 4002: 3995: 3987: 3983: 3979: 3975: 3971: 3967: 3963: 3956: 3948: 3944: 3939: 3934: 3930: 3926: 3922: 3918: 3914: 3907: 3899: 3895: 3891: 3887: 3883: 3879: 3872: 3864: 3860: 3856: 3852: 3848: 3844: 3840: 3836: 3828: 3826: 3817: 3813: 3809: 3805: 3801: 3797: 3790: 3782: 3778: 3774: 3770: 3766: 3762: 3755: 3747: 3743: 3739: 3735: 3731: 3727: 3720: 3712: 3708: 3704: 3700: 3696: 3692: 3685: 3683: 3681: 3672: 3668: 3664: 3660: 3656: 3652: 3645: 3643: 3641: 3632: 3628: 3624: 3620: 3616: 3612: 3604: 3596: 3592: 3588: 3584: 3580: 3576: 3568: 3566: 3564: 3555: 3551: 3547: 3543: 3539: 3535: 3527: 3525: 3523: 3521: 3512: 3510:9781496318299 3506: 3502: 3495: 3493: 3484: 3480: 3475: 3470: 3466: 3462: 3458: 3454: 3450: 3443: 3435: 3431: 3426: 3421: 3417: 3413: 3409: 3405: 3401: 3394: 3386: 3382: 3378: 3374: 3370: 3366: 3362: 3358: 3351: 3343: 3336: 3328: 3321: 3319: 3317: 3315: 3313: 3304: 3297: 3295: 3293: 3284: 3280: 3276: 3272: 3268: 3264: 3260: 3256: 3255:CNS Spectrums 3249: 3247: 3238: 3234: 3230: 3226: 3222: 3218: 3214: 3210: 3203: 3201: 3192: 3188: 3183: 3178: 3174: 3170: 3166: 3162: 3158: 3151: 3143: 3139: 3135: 3131: 3127: 3123: 3119: 3115: 3108: 3106: 3104: 3095: 3091: 3087: 3083: 3076: 3062:on 2014-06-11 3058: 3054: 3050: 3043: 3036: 3034: 3025: 3021: 3017: 3013: 3009: 3005: 3001: 2997: 2990: 2982: 2978: 2973: 2968: 2964: 2960: 2956: 2952: 2948: 2941: 2939: 2930: 2926: 2922: 2918: 2914: 2910: 2903: 2901: 2892: 2888: 2884: 2880: 2876: 2872: 2868: 2864: 2857: 2841: 2837: 2836: 2831: 2824: 2816: 2812: 2808: 2804: 2800: 2796: 2789: 2773: 2767: 2765: 2763: 2761: 2759: 2750: 2746: 2742: 2738: 2734: 2730: 2726: 2722: 2715: 2713: 2704: 2700: 2696: 2692: 2688: 2684: 2680: 2676: 2669: 2667: 2650: 2646: 2640: 2621: 2614: 2608: 2592: 2588: 2582: 2580: 2578: 2576: 2574: 2572: 2570: 2568: 2566: 2564: 2562: 2560: 2551: 2547: 2543: 2539: 2535: 2531: 2524: 2522: 2520: 2518: 2509: 2505: 2501: 2497: 2493: 2489: 2485: 2481: 2473: 2465: 2461: 2457: 2453: 2449: 2442: 2440: 2431: 2427: 2423: 2419: 2415: 2411: 2407: 2403: 2396: 2394: 2385: 2381: 2376: 2371: 2367: 2363: 2359: 2355: 2351: 2344: 2336: 2332: 2328: 2324: 2320: 2316: 2309: 2301: 2297: 2293: 2289: 2285: 2281: 2277: 2273: 2266: 2258: 2254: 2250: 2246: 2242: 2238: 2231: 2223: 2219: 2215: 2211: 2207: 2203: 2202:CNS Spectrums 2199: 2192: 2178: 2174: 2167: 2163: 2153: 2150: 2148: 2145: 2143: 2140: 2138: 2135: 2134: 2128: 2119: 2110: 2101: 2088: 2086: 2082: 2071: 2069: 2064: 2052: 2049: 2047: 2044: 2042: 2039: 2037: 2034: 2032: 2029: 2027: 2024: 2022: 2019: 2017: 2014: 2012: 2009: 2007: 2004: 2003: 2002: 1993: 1980: 1977: 1973: 1969: 1964: 1960: 1956: 1946: 1932: 1930: 1926: 1925:Amitriptyline 1922: 1918: 1914: 1910: 1902: 1898: 1893: 1888: 1878: 1876: 1872: 1868: 1864: 1860: 1849: 1840: 1838: 1834: 1830: 1826: 1822: 1818: 1814: 1810: 1806: 1796: 1787: 1785: 1781: 1777: 1773: 1769: 1764: 1763:noradrenergic 1760: 1755: 1753: 1749: 1745: 1741: 1737: 1733: 1729: 1725: 1721: 1717: 1713: 1709: 1705: 1701: 1691: 1689: 1685: 1681: 1677: 1627: 1623: 1620: 1617: 1614: 1611: 1609: 1606: 1605: 1601: 1598: 1595: 1592: 1589: 1587: 1584: 1583: 1579: 1577: 1574: 1572: 1569: 1567: 1564: 1563: 1559: 1556: 1553: 1550: 1547: 1545: 1542: 1541: 1537: 1534: 1531: 1528: 1525: 1523: 1520: 1519: 1515: 1512: 1509: 1506: 1503: 1501: 1498: 1497: 1488: 1482: 1474: 1468: 1467: 1439: 1421: 1419: 1415: 1411: 1407: 1403: 1399: 1389: 1386: 1380: 1378: 1374: 1370: 1366: 1365:extracellular 1362: 1358: 1353: 1349: 1339: 1323: 1319: 1317: 1314: 1312: 1309: 1307: 1304: 1302: 1299: 1296: 1293: 1290: 1287: 1284: 1281: 1278: 1275: 1274: 1273: 1265: 1256: 1242: 1239: 1235: 1224: 1222: 1218: 1214: 1210: 1206: 1205:lipophilicity 1202: 1198: 1194: 1190: 1188: 1184: 1178: 1174: 1169: 1167: 1166:pharmacophore 1162: 1158: 1148: 1135: 1131: 1129: 1125: 1121: 1116: 1115:aromatic ring 1112: 1108: 1095: 1091: 1089: 1085: 1081: 1076: 1060: 1058: 1053: 1051: 1047: 1042: 1033: 1031: 1023: 1016: 1009: 1004: 1002: 998: 990: 986: 976: 974: 970: 966: 962: 958: 954: 940: 938: 933: 926: 917: 912: 910: 909:smooth muscle 902: 898: 894: 890: 886: 885:autoreceptors 882: 878: 877:autoreceptors 865: 863: 858: 850: 841: 838: 834: 830: 813: 808: 794: 790: 788: 784: 780: 776: 772: 767: 765: 761: 756: 755:catecholamine 751: 749: 745: 741: 737: 733: 729: 725: 721: 717: 713: 709: 705: 701: 695: 680: 676: 671: 667: 662: 658: 655: 650: 647: 644: 641: 638: 635: 634: 633: 630: 628: 625: 624: 619: 615: 611: 606: 602: 599: 594: 593: 592: 589: 587: 584: 583: 579: 575: 571: 567: 562: 558: 555: 551: 548: 547: 546: 543: 541: 538: 537: 533: 529: 528:significantly 525: 519: 515: 512: 507: 504: 503: 502: 495: 493: 490: 489: 485: 481: 475: 471: 468: 463: 462: 461: 458: 456: 453: 452: 448: 444: 443:low back pain 440: 436: 432: 428: 424: 420: 416: 410: 406: 403: 399: 396: 393: 392:low back pain 389: 387: 384: 381: 378: 375: 374: 373: 371: 367: 365: 362: 361: 356: 351: 347: 344: 339: 338: 337: 335: 331: 329: 326: 325: 321: 318: 316:Approval Year 315: 312: 309: 306: 305: 302: 300: 296: 287: 278: 276: 272: 268: 263: 261: 256: 252: 248: 244: 239: 237: 233: 229: 225: 221: 217: 213: 209: 205: 201: 197: 193: 189: 185: 181: 177: 173: 170: 166: 162: 155: 145: 141: 136: 132: 128: 126: 122: 117: 114: 110: 107: 105: 101: 98: 94: 90: 86: 82: 79: 75: 71: 69: 65: 60: 55: 50: 45: 42: 41: 36: 31: 19: 10351: 10350: 10335: 10323: 10320: 10310: 10220:Bietaserpine 10192:Amphetamines 10115:Mifepristone 10105:Medifoxamine 9987: 9930:Clomipramine 9925:Cianopramine 9916: 9769:Diclofensine 9739:Brasofensine 9715: 9639: 9627:Vortioxetine 9578: 9497:Escitalopram 9453: 9375:Indeloxazine 9367: 9304: 9287:Oxaprotiline 9268: 9256:Trimipramine 9211:Clomipramine 9206:Cianopramine 9201:Butriptyline 9192: 9045:Diclofensine 9015:Brasofensine 8991: 8915: 8903:Solriamfetol 8829: 8812:Teniloxazine 8772:Esreboxetine 8743: 8675:Solriamfetol 8595:Medifoxamine 8485:Dimethocaine 8475:Diclofensine 8447: 8399: 8287:Difluoropine 8282:Dichloropane 8267:Brasofensine 8253: 8241:Pyrovalerone 8217: 8142:Piperidines: 8141: 8091:Piperazines: 8090: 7937:Cannabinoids 7922:Benfotiamine 7751: 7733:fibromyalgia 7590:Lorpiprazole 7580:Fabomotizole 7570:Benzoctamine 7472:Vortioxetine 7448: 7415:clomipramine 7370:escitalopram 7257:Carisoprodol 7237:Barbiturates 7228: 7113: 7079:Tandospirone 6939:Oxitriptan ( 6931: 6815:aripiprazole 6773: 6722:Metralindole 6713: 6683: 6673: 6652:Pivhydrazine 6642:Pheniprazine 6588: 6494:Trimipramine 6484:Quinupramine 6384:Clomipramine 6379:Butriptyline 6302:Teniloxazine 6297:Tandospirone 6282:Metryptamine 6277:Medifoxamine 6262:Indeloxazine 6216:Vortioxetine 5978:Escitalopram 5857: 5853: 5843: 5808: 5804: 5794: 5761: 5757: 5750: 5715: 5711: 5666:(1): 30–34. 5663: 5659: 5619: 5615: 5605: 5593:. Retrieved 5586:the original 5581: 5569: 5558:. Retrieved 5546: 5536: 5501: 5497: 5487: 5462:2158/1132671 5444: 5440: 5434: 5407: 5403: 5393: 5358: 5354: 5344: 5322:(1): 22–34. 5319: 5315: 5308: 5296:. Retrieved 5286: 5251: 5247: 5237: 5202: 5198: 5188: 5153: 5149: 5103: 5099: 5093: 5082:. Retrieved 5078: 5069: 5042: 5038: 5014:. Retrieved 5010: 5001: 4966: 4962: 4932: 4928: 4922: 4903: 4899: 4889: 4867:(1): 31–37. 4864: 4860: 4853: 4842:. Retrieved 4838: 4829: 4794: 4790: 4780: 4772: 4767: 4730: 4726: 4716: 4683: 4679: 4658:. Retrieved 4653: 4636: 4601: 4597: 4555: 4551: 4526:. Retrieved 4521: 4491:. Retrieved 4486: 4456:. Retrieved 4451: 4402: 4398: 4392: 4378: 4345: 4341: 4299:(1): 41–53. 4296: 4292: 4282: 4255: 4251: 4241: 4224: 4218: 4165: 4161: 4151: 4140:. Retrieved 4136: 4127: 4092: 4088: 4078: 4045: 4041: 4035: 4011:(6): 10–14. 4008: 4004: 3994: 3969: 3965: 3955: 3920: 3916: 3906: 3881: 3877: 3871: 3838: 3834: 3799: 3795: 3789: 3764: 3760: 3754: 3729: 3725: 3719: 3694: 3690: 3654: 3650: 3614: 3610: 3603: 3578: 3574: 3537: 3533: 3500: 3459:(1): 49–58. 3456: 3452: 3442: 3407: 3403: 3393: 3360: 3356: 3350: 3341: 3335: 3326: 3302: 3258: 3254: 3212: 3208: 3164: 3160: 3150: 3117: 3113: 3085: 3081: 3075: 3064:. Retrieved 3057:the original 3052: 3048: 2999: 2995: 2989: 2954: 2950: 2912: 2908: 2866: 2862: 2856: 2844:. Retrieved 2840:the original 2833: 2823: 2798: 2794: 2788: 2776:. Retrieved 2727:(1): 34–35. 2724: 2720: 2678: 2674: 2653:. Retrieved 2648: 2639: 2627:. Retrieved 2620:the original 2607: 2595:. Retrieved 2590: 2533: 2529: 2483: 2479: 2472: 2447: 2405: 2401: 2357: 2353: 2343: 2318: 2314: 2308: 2278:(3): 13–17. 2275: 2271: 2265: 2240: 2236: 2230: 2205: 2201: 2191: 2180:. Retrieved 2176: 2166: 2125: 2116: 2107: 2099: 2085:escitalopram 2081:escitalopram 2077: 2060: 2046:Hyperthermia 2041:Hypertension 1999: 1991: 1952: 1943: 1906: 1855: 1846: 1819:or adding a 1802: 1793: 1790:Side effects 1756: 1697: 1673: 1629:All of the K 1405: 1395: 1381: 1345: 1336: 1328:Pharmacology 1316:Fibromyalgia 1271: 1262: 1253: 1230: 1196: 1192: 1186: 1182: 1170: 1156: 1153: 1119: 1105: 1084:phenyl group 1071: 1054: 1043: 1039: 1005: 982: 969:caudal raphe 946: 934: 913: 866: 859: 855: 804: 768: 760:pathogenesis 752: 744:side effects 712:tuberculosis 708:psychoactive 697: 612:A dual weak 526:Shown to be 505:Fibromyalgia 484:levorotating 379:Fibromyalgia 369: 333: 292: 264: 240: 234:(SSRIs) and 164: 160: 159: 138:Legal status 38: 10363:Adrenergics 10290:Valbenazine 10280:Rose bengal 10225:Deserpidine 10196:amphetamine 10146:levorphanol 10090:Dextrorphan 10043:ziprasidone 10025:pheniramine 9960:Lofepramine 9940:Desipramine 9889:Tesofensine 9879:Sibutramine 9854:Perafensine 9814:JNJ-7925476 9809:Indatraline 9754:Dasotraline 9724:Amifitadine 9703:Venlafaxine 9683:Milnacipran 9582:Etoperidone 9562:Seproxetine 9552:Pirandamine 9532:Omiloxetine 9512:Fluvoxamine 9472:Cericlamine 9462:Alaproclate 9409:levorphanol 9338:ziprasidone 9320:pheniramine 9292:Setiptiline 9277:Maprotiline 9236:Lofepramine 9216:Desipramine 9165:Tesofensine 9155:Sibutramine 9130:Perafensine 9090:JNJ-7925476 9085:Indatraline 9030:Dasotraline 9000:Amifitadine 8979:Venlafaxine 8954:Milnacipran 8883:Nomifensine 8848:Fencamfamin 8777:Lortalamine 8767:Edivoxetine 8757:Ciclazindol 8752:Alseroxylon 8700:Venlafaxine 8680:Tametraline 8670:Sibutramine 8645:Perafensine 8625:Nomifensine 8555:Indatraline 8530:Fencamfamin 8505:DOV-216,303 8500:DOV-102,677 8460:Dasotraline 8455:Ciclazindol 8413:Armodafinil 8408:Amifitadine 8357:Tesofensine 8165:Difemetorex 7977:hydrocodone 7895:desipramine 7857:lamotrigine 7841:mirogabalin 7765:milnacipran 7671:from market 7600:Mepiprazole 7585:Hydroxyzine 7575:Cycloserine 7553:propranolol 7495:Flupentixol 7452:Agomelatine 7430:mirtazapine 7251:meprobamate 7185:Fludiazepam 7160:Clotiazepam 7155:Clorazepate 7036:Anxiolytics 6978:from market 6921:brexanolone 6835:risperidone 6732:Moclobemide 6714:Reversible: 6674:Reversible: 6597:Iproclozide 6532:Setiptiline 6527:Mirtazapine 6517:Maprotiline 6474:Propizepine 6459:Noxiptiline 6444:Metapramine 6434:Lofepramine 6404:Dimetacrine 6394:Desipramine 6267:Flupentixol 6252:Etryptamine 6237:Amisulpride 6232:Agomelatine 6178:Etoperidone 6155:Setiptiline 6150:Mirtazapine 6122:Nomifensine 6079:Atomoxetine 6056:Venlafaxine 6046:Milnacipran 5988:Fluvoxamine 5860:: e072415. 4528:12 February 4493:12 February 4458:12 February 4137:Mayo Clinic 2778:2 September 2655:12 February 2597:12 February 2360:(1): 1–21. 2036:Hypotension 2031:Tachycardia 1968:venlafaxine 1935:Precautions 1921:photophobia 1688:Milnacipran 1676:venlafaxine 1651:based on IC 1637:values are 1586:Milnacipran 1566:Atomoxetine 1500:Venlafaxine 1420:, as well. 1268:Indications 1142:Milnacipran 1107:Venlafaxine 1075:substituent 973:spinal cord 963:across the 953:-tryptophan 775:venlafaxine 627:Venlafaxine 574:weight loss 540:Sibutramine 521:Milnacipran 492:Milnacipran 295:venlafaxine 281:Medications 273:(TCAs) and 245:(SERT) and 202:(OCD), and 190:(FMS), and 172:medications 144:In Wikidata 10339:SoRI-20041 10332:SoRI-20040 10260:Ketanserin 10187:Amiodarone 10150:tapentadol 10110:Mesembrine 10080:Delucemine 10057:esketamine 9970:Pipofezine 9955:Imipramine 9874:SEP-228432 9869:SEP-228431 9839:Nefazodone 9824:Liafensine 9794:Fezolamine 9784:DOV-216303 9779:DOV-102677 9734:Bicifadine 9729:Ansofaxine 9668:Eclanamine 9663:Duloxetine 9648:Bicifadine 9622:Vilazodone 9592:Lubazodone 9587:Litoxetine 9572:Zimelidine 9567:Sertraline 9542:Paroxetine 9537:Panuramine 9507:Fluoxetine 9502:Femoxetine 9482:Dapoxetine 9477:Citalopram 9401:tapentadol 9380:Nefazodone 9363:Ephenidine 9358:Dopexamine 9241:Melitracen 9231:Imipramine 9150:SEP-228432 9145:SEP-228431 9115:Nefazodone 9100:Liafensine 9070:Fezolamine 9060:DOV-216303 9055:DOV-102677 9010:Bicifadine 9005:Ansofaxine 8964:Nafenodone 8939:Eclanamine 8934:Duloxetine 8893:Radafaxine 8873:Manifaxine 8858:Lefetamine 8833:Amineptine 8817:Viloxazine 8792:Reboxetine 8787:Nisoxetine 8665:Sertraline 8655:Radafaxine 8640:Oroxylin A 8585:Manifaxine 8575:Liafensine 8565:Lefetamine 8545:GYKI-52895 8535:Fezolamine 8520:Esketamine 8515:Ephenidine 8438:BTS 74,398 8428:Ansofaxine 8423:Amineptine 8302:FP-β-CPPIT 8297:FE-β-CPPIT 8236:Prolintane 8129:Vanoxerine 8124:Nefazodone 8001:tapentadol 7945:dronabinol 7901:Ziconotide 7873:Mexiletine 7853:lacosamide 7837:pregabalin 7833:gabapentin 7806:tapentadol 7761:duloxetine 7615:Oxaflozane 7543:guanfacine 7490:Quetiapine 7467:Vilazodone 7462:Tianeptine 7445:phenelzine 7385:duloxetine 7343:Pregabalin 7328:Gabapentin 7247:Carbamates 7210:Nordazepam 7165:Cloxazolam 7150:Clonazepam 7130:Bromazepam 7125:Alprazolam 7120:Adinazolam 6953:Tryptophan 6925:zuranolone 6831:quetiapine 6827:olanzapine 6823:lurasidone 6777:Selegiline 6767:-selective 6747:Toloxatone 6742:Tetrindole 6737:Pirlindole 6717:Eprobemide 6707:-selective 6687:Bifemelane 6677:Caroxazone 6637:Phenelzine 6622:Mebanazine 6602:Iproniazid 6489:Tianeptine 6469:Pipofezine 6439:Melitracen 6419:Imipramine 6399:Dibenzepin 6359:Amineptine 6307:Tianeptine 6292:Pivagabine 6287:Oxaflozane 6247:Esketamine 6211:Vilazodone 6183:Nefazodone 6112:Amineptine 6089:Viloxazine 6084:Reboxetine 6036:Duloxetine 6008:Zimelidine 6003:Sertraline 5998:Paroxetine 5983:Fluoxetine 5973:Citalopram 5560:2019-11-21 5547:StatPearls 5294:. UpToDate 5084:2019-10-23 5079:poison.org 5016:2019-11-21 4844:2019-10-21 4839:poison.org 4142:2019-10-24 3410:: 212290. 3066:2014-03-05 3002:(1): 1–8. 2182:2024-01-09 2158:References 2113:Geriatrics 2104:Pediatrics 2057:Management 2006:Somnolence 1955:withdrawal 1929:citalopram 1917:nyctalopia 1913:palinopsia 1869:, such as 1833:vardenafil 1831:(Cialis), 1827:(Viagra), 1825:sildenafil 1813:anorgasmia 1809:anorgasmia 1716:analgesics 1684:duloxetine 1544:Duloxetine 1357:inhibiting 1250:Depression 1234:morpholine 1080:paroxetine 1001:previously 961:tryptophan 895:-mediated 893:cyclic AMP 812:metabolism 764:fluoxetine 740:depression 728:Imipramine 700:iproniazid 692:See also: 427:nefazodone 412:Duloxetine 364:Duloxetine 310:Brand name 307:Medication 249:(NAT) are 241:The human 192:menopausal 131:D000068760 81:Depression 54:Duloxetine 40:Drug class 10352:See also: 10327:SoRI-9804 10275:Reserpine 10245:GBR-12935 10240:Efavirenz 10160:Roxindole 10138:methadone 10125:N-Me-5-HT 10095:Efavirenz 10053:3-MeO-PCP 9996:Amoxapine 9864:Pridefine 9834:Naphyrone 9698:Tofenacin 9617:Trazodone 9607:SB-649915 9602:Quipazine 9597:LY-393558 9522:Ifoxetine 9517:Indalpine 9393:methadone 9282:Mianserin 9272:Amoxapine 9140:Pridefine 9110:Naphyrone 8974:Tofenacin 8924:CP-39,332 8843:Fencamine 8838:Bupropion 8807:Tandamine 8802:Talsupram 8762:Daledalin 8660:Rimcazole 8650:Pridefine 8615:Modafinil 8540:Fluorenol 8510:Efavirenz 8443:Bupropion 8403:Adrafinil 8367:Tropoxane 8257:Altropane 8254:Tropanes: 8231:Naphyrone 8195:Pipradrol 8114:GBR-13098 8109:GBR-13069 8104:GBR-12935 8099:GBR-12783 7989:methadone 7985:oxycodone 7967:methadone 7932:Bupropion 7867:lidocaine 7788:dosulepin 7681:Phase III 7669:Withdrawn 7650:Validolum 7645:Tofisopam 7640:Tiagabine 7630:Picamilon 7610:Opipramol 7535:clonidine 7457:Bupropion 7400:trazodone 7290:Zopiclone 7282:Hypnotics 7272:Etifoxine 7220:Pinazepam 7205:Medazepam 7200:Lorazepam 7195:Ketazolam 7190:Halazepam 7135:Camazepam 7069:Buspirone 6988:Phase III 6976:Withdrawn 6841:Buspirone 6727:Minaprine 6662:Tedizolid 6657:Safrazine 6632:Octamoxin 6627:Nialamide 6617:Linezolid 6612:Isoniazid 6522:Mianserin 6464:Opipramol 6429:Iprindole 6409:Dosulepin 6374:Amoxapine 6330:Tricyclic 6188:Trazodone 6145:Mianserin 6117:Bupropion 6051:Tofenacin 5993:Indalpine 5942:Specific 5128:145217439 4650:Database" 4210:250646781 4184:1476-5578 4095:(9): 63. 3833:agents". 2846:8 October 2675:CNS Drugs 2629:29 August 2300:205396280 2222:1092-8529 2096:Pregnancy 1976:half-life 1871:ibuprofen 1829:tadalafil 1817:bupropion 1805:anhedonia 1784:mydriasis 1752:myoclonus 1732:linezolid 1418:microglia 1385:microglia 1259:Analgesic 1050:half-life 1030:receptors 971:into the 698:In 1952, 578:withdrawn 423:hepatitis 368:Cymbalta 220:serotonin 10416:Category 10406:Medicine 10314:Luteolin 10265:Lobeline 10255:Ibogaine 10154:tramadol 10100:Hypidone 10061:ketamine 10039:loxapine 9899:Tropanes 9829:Mazindol 9819:JZ-IV-10 9653:CP-39332 9612:TGBA01AD 9405:tramadol 9348:ketamine 9334:loxapine 9175:Tropanes 9105:Mazindol 9095:JZ-IV-10 8797:Talopram 8782:Mazindol 8747:Amedalin 8605:Metaphit 8600:Mesocarb 8590:Mazindol 8560:Ketamine 8362:Troparil 8119:JJC8-088 7997:tramadol 7981:morphine 7959:ketamine 7949:nabilone 7941:cannabis 7810:tramadol 7625:Phenibut 7605:Nicotine 7525:prazosin 7338:Phenibut 7318:blockers 7225:Prazepam 7215:Oxazepam 7180:Etizolam 7170:Diazepam 7145:Clobazam 7074:Gepirone 7061:agonists 6914:GABAkine 6592:Benmoxin 6548:Tiazesim 6272:Ketamine 6257:Gepirone 5884:36725015 5835:25037293 5786:29031880 5778:12364842 5742:29588049 5690:30123033 5638:17394446 5555:29493999 5528:24167687 5479:51677365 5471:30016772 5426:30016772 5385:26834969 5336:17445831 5278:35235167 5229:26579809 5199:Medicine 5180:21743381 5120:18515448 5061:18625822 4993:29955469 4941:16848675 4881:11838623 4821:29315692 4759:29158677 4708:37959124 4700:15784664 4628:23397050 4574:28503727 4522:DailyMed 4487:DailyMed 4452:DailyMed 4427:37792842 4419:19810918 4370:39281923 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1088:aromatic 783:dopamine 750:issues. 748:toxicity 716:dopamine 586:Tramadol 500:Impulsor 332:Pristiq 226:. 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