Tricyclic antidepressant

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Tricyclic antidepressant
Drug class
Chemical structure of the prototypical and first marketed tricyclic antidepressant imipramine. Notice its three rings.
Class identifiers
Chemical class Tricyclic
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MeSH D000929
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In Wikidata

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. [1] They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.


Although TCAs are sometimes prescribed for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). Adverse effects have been found to be of a similar level between TCAs and SSRIs. [2]


The TCAs were developed amid the "explosive birth" of psychopharmacology in the early 1950s. The story begins with the synthesis of chlorpromazine in December 1950 by Rhône-Poulenc's chief chemist, Paul Charpentier, from synthetic antihistamines developed by Rhône-Poulenc in the 1940s. [3] Its psychiatric effects were first noticed at a hospital in Paris in 1952. The first widely used psychiatric drug, by 1955 it was already generating significant revenue as an antipsychotic. [4] Research chemists quickly began to explore other derivatives of chlorpromazine.

The first TCA reported for the treatment of depression was imipramine, a dibenzazepine analogue of chlorpromazine code-named G22355. It was not originally targeted for the treatment of depression. The drug's tendency to induce manic effects was "later described as 'in some patients, quite disastrous'". The paradoxical observation of a sedative inducing mania led to testing with depressed patients. The first trial of imipramine took place in 1955 and the first report of antidepressant effects was published by Swiss psychiatrist Roland Kuhn in 1957. [3] Some testing of Geigy's imipramine, then known as Tofranil, took place at the Münsterlingen Hospital near Konstanz. [4] Geigy later became Ciba-Geigy and eventually Novartis.

Dibenzazepine derivatives are described in U.S. patent 3,074,931 issued 1963-01-22 by assignment to Smith Kline & French Laboratories. The compounds described share a tricyclic backbone different from the backbone of the TCA amitriptyline.

Merck introduced the second member of the TCA family, amitriptyline (Elavil), in 1961. [4] This compound has a different three-ring structure than imipramine.

Medical uses

The TCAs are used primarily in the clinical treatment of mood disorders such as major depressive disorder (MDD), dysthymia, and treatment-resistant variants. They are also used in the treatment of a number of other medical disorders, including cyclic vomiting syndrome (CVS) and anxiety disorders such as generalized anxiety disorder (GAD), social phobia (SP) also known as social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), and panic disorder (PD), post-traumatic stress disorder (PTSD), body dysmorphic disorder (BDD), eating disorders like anorexia nervosa and bulimia nervosa, certain personality disorders such as borderline personality disorder (BPD), neurological disorders such as attention-deficit hyperactivity disorder (ADHD), [5] Parkinson's disease [6] as well as chronic pain, neuralgia or neuropathic pain, and fibromyalgia, headache, or migraine, smoking cessation, tourette syndrome, trichotillomania, irritable bowel syndrome (IBS), interstitial cystitis (IC), nocturnal enuresis (NE), [7] narcolepsy, insomnia, pathological crying and/or laughing, chronic hiccups, ciguatera poisoning, and as an adjunct in schizophrenia.

Nortriptyline and desipramine may be preferred medications over other TCAs among older adults due to their reduced anticholinergic effects, diminished cardiac toxicity, and more linear pharmacokinetics. [8] [9]

Clinical depression

For many years the TCAs were the first choice for pharmacological treatment of major depression. Although they are still considered to be highly effective, they have been increasingly replaced by antidepressants with an improved safety and side-effect profile, such as the SSRIs and other newer antidepressants such as the novel reversible MAOI moclobemide. However, tricyclic antidepressants are possibly more effective in treating melancholic depression than other antidepressant drug classes. [10] Newer antidepressants are thought to have fewer and less severe side effects and are also thought to be less likely to result in injury or death if used in a suicide attempt, as the doses required for clinical treatment and potentially lethal overdose (see therapeutic index) are far wider in comparison. A 2024 systematic review concluded that, in the treatment of depression, "[t]he long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events," but cautioned that "results were based on low and very low certainty evidence," owing to the poor quality of the clinical trials reviewed. [11]

Nonetheless, the TCAs are commonly prescribed for treatment-resistant depression that has failed to respond to therapy with newer antidepressants, they also tend to have fewer emotional blunting and sexual side effects than SSRI antidepressants. [12] They are not considered addictive and are somewhat preferable to the monoamine oxidase inhibitors (MAOIs). The side effects of the TCAs usually come to prominence before the therapeutic benefits against depression and/or anxiety do, and for this reason, they may potentially be somewhat dangerous, as volition can be increased, possibly giving the patient a greater desire to attempt or commit suicide. [13]

Attention-deficit hyperactivity disorder

The TCAs were used in the past in the clinical treatment of ADHD, [14] though they are not typically used anymore, having been replaced by more effective agents with fewer side effects such as atomoxetine (Strattera, Tomoxetin) and stimulants like methylphenidate (Ritalin, Focalin, Concerta), and amphetamine (Adderall, Attentin, Dexedrine, Vyvanse). ADHD is thought to be caused by an insufficiency of dopamine and norepinephrine activity in the prefrontal cortex of the brain. [15] Most of the TCAs inhibit the reuptake of norepinephrine, though not dopamine, and as a result, they show some efficacy in remedying the disorder. [16] Notably, the TCAs are more effective in treating the behavioral aspects of ADHD than the cognitive deficits, as they help limit hyperactivity and impulsivity, but have little to no benefits on attention. [17]

Chronic pain

The TCAs show efficacy in the clinical treatment of a number of different types of chronic pain, notably neuralgia or neuropathic pain and fibromyalgia. [18] [19] The precise mechanism of action in explanation of their analgesic efficacy is unclear, but it is thought that they indirectly modulate the opioid system in the brain downstream via serotonergic and noradrenergic neuromodulation, among other properties. [20] [21] [22] They are also effective in migraine prophylaxis, though not in the instant relief of an acute migraine attack. They may also be effective to prevent chronic tension headaches.

Side effects

Many side effects may be related to the antimuscarinic properties of the TCAs. Such side effects are relatively common and may include dry mouth, dry nose, blurry vision, lowered gastrointestinal motility or constipation, urinary retention, cognitive and/or memory impairment, and increased body temperature.

Other side effects may include drowsiness, anxiety, emotional blunting (apathy/anhedonia), confusion, restlessness, dizziness, akathisia, hypersensitivity, changes in appetite and weight, sweating, muscle twitches, weakness, nausea and vomiting, hypotension, tachycardia, and rarely, irregular heart rhythms. Twitching, hallucinations, delirium and coma are also some of the toxic effects caused by overdose. [23] Rhabdomyolysis or muscle breakdown has been rarely reported with this class of drugs as well. [24]

Tolerance to these adverse effects of these drugs often develops if treatment is continued. Side effects may also be less troublesome if treatment is initiated with low doses and then gradually increased, although this may also delay the beneficial effects.

TCAs can behave like class 1A antiarrhythmics, as such, they can theoretically terminate ventricular fibrillation, decrease cardiac contractility and increase collateral blood circulation to ischemic heart muscle. Naturally, in overdose, they can be cardiotoxic, prolonging heart rhythms and increasing myocardial irritability.

New research has also revealed compelling evidence of a link between long-term use of anticholinergic medications like TCAs and dementia. [25] Although many studies have investigated this link, this was the first study to use a long-term approach (over seven years) to find that dementias associated with anticholinergics may not be reversible even years after drug use stops. [26] Anticholinergic drugs block the action of acetylcholine, which transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory.


Antidepressants in general may produce withdrawal. However, since the term "withdrawal" has been linked to addiction to recreational drugs like opioids, the medical profession and pharmaceutical public relations prefer that a different term be used, hence "discontinuation syndrome." [27] Discontinuation symptoms can be managed by a gradual reduction in dosage over a period of weeks or months to minimise symptoms. [28] In tricyclics, discontinuation syndrome symptoms include anxiety, insomnia, headache, nausea, malaise, or motor disturbance. [29]


TCA overdose is a significant cause of fatal drug poisoning. The severe morbidity and mortality associated with these drugs is well documented due to their cardiovascular and neurological toxicity. Additionally, it is a serious problem in the pediatric population due to their inherent toxicity [30] and the availability of these in the home when prescribed for bed-wetting and depression. In the event of a known or suspected overdose, medical assistance should be sought immediately.

A number of treatments are effective in a TCA overdose.

An overdose on TCA is especially fatal as it is rapidly absorbed from the GI tract in the alkaline conditions of the small intestines. As a result, toxicity often becomes apparent in the first hour after an overdose. However, symptoms may take several hours to appear if a mixed overdose has caused delayed gastric emptying.

Many of the initial signs are those associated to the anticholinergic effects of TCAs such as dry mouth, blurred vision, urinary retention, constipation, dizziness, and emesis (or vomiting). Due to the location of norepinephrine receptors all over the body, many physical signs are also associated with a TCA overdose: [31]

  1. Anticholinergic effects: altered mental status (e.g., agitation, confusion, lethargy, etc.), resting sinus tachycardia, dry mouth, mydriasis, blurred vision, fever
  2. Cardiac effects: hypertension (early and transient, should not be treated), tachycardia, orthostasis and hypotension, arrhythmias (including ventricular tachycardia and ventricular fibrillation, most serious consequence), ECG changes (prolonged QRS, QT, and PR intervals)
  3. CNS effects: syncope, seizure, coma, myoclonus, hyperreflexia, convulsions, drowsiness
  4. Pulmonary effects: hypoventilation resulting from CNS depression [32]
  5. Gastrointestinal effects: decreased or absent bowel sounds

Treatment of TCA overdose depends on severity of symptoms:

Initially, gastric decontamination of the patient is achieved by administering, either orally or via a nasogastric tube, activated charcoal pre-mixed with water, which adsorbs the drug in the gastrointestinal tract (most useful if given within 2 hours of drug ingestion). Other decontamination methods such as stomach pumps, gastric lavage, whole bowel irrigation, or (ipecac induced) emesis, are not  recommended in TCA poisoning.

If there is metabolic acidosis, intravenous infusion of sodium bicarbonate is recommended by, the UK and Ireland poisons advice database (TCAs are protein bound and become less bound in more acidic conditions, so by reversing the acidosis, protein binding increases and bioavailability thus decreases – the sodium load may also help to reverse the Na+ channel blocking effects of the TCA).


The TCAs are highly metabolised by the cytochrome P450 (CYP) hepatic enzymes. Drugs that inhibit cytochrome P450 (for example cimetidine, methylphenidate, fluoxetine, antipsychotics, and calcium channel blockers) may produce decreases in the TCAs' metabolism, leading to increases in their blood concentrations and accompanying toxicity. [33] Drugs that prolong the QT interval including antiarrhythmics such as quinidine, the antihistamines astemizole and terfenadine, and some antipsychotics may increase the chance of ventricular dysrhythmias. TCAs may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. Side effects may also be enhanced by other drugs that have antimuscarinic properties.


The majority of the TCAs act primarily as SNRIs by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET), which results in an elevation of the synaptic concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission. [34] [35] Notably, with the sole exception of amineptine, the TCAs have weak affinity for the dopamine transporter (DAT), and therefore have low efficacy as dopamine reuptake inhibitors (DRIs). [34] Both serotonin and norepinephrine have been highly implicated in depression and anxiety, and it has been shown that facilitation of their activity has beneficial effects on these mental disorders. [36]

In addition to their reuptake inhibition, many TCAs also have high affinity as antagonists at the 5-HT2 [37] (5-HT2A [38] and 5-HT2C [38] ), 5-HT6, [39] 5-HT7, [40] α1-adrenergic, [37] and NMDA receptors, [41] and as agonists at the sigma receptors [42] (σ1 [42] and σ2 [43] ), some of which may contribute to their therapeutic efficacy, as well as their side effects. [44] The TCAs also have varying but typically high affinity for antagonising the H1 [37] and H2 [45] [46] histamine receptors, as well as the muscarinic acetylcholine receptors. [37] As a result, they also act as potent antihistamines and anticholinergics. These properties are often beneficial in antidepressants, especially with comorbid anxiety, as it provides a sedative effect. [47]

Most, if not all, of the TCAs also potently inhibit sodium channels and L-type calcium channels, and therefore act as sodium channel blockers and calcium channel blockers, respectively. [48] [49] The former property is responsible for the high mortality rate upon overdose seen with the TCAs via cardiotoxicity. [50] It may also be involved in their efficacy as analgesics, however. [51]

In summary, tricyclic antidepressants can act through NMDA antagonism, opioidergic effects, sodium, potassium and calcium channel blocking, through interfering with the reuptake of serotonin and acting as antagonists to SHAM (serotonin, histamine, alpha, muscarinic) receptors.  Thus their dangerous side effect profile limits their use in daily practice.

Binding profiles

The binding profiles of various TCAs and some metabolites in terms of their affinities (Ki, nM) for various receptors and transporters are as follows: [52]

Compound SERT Tooltip Serotonin transporter NET Tooltip Norepinephrine transporter DAT Tooltip Dopamine transporter 5-HT1A 5-HT2A 5-HT2C 5-HT6 5-HT7 α1 α2 D2 H1 H2 mACh Tooltip Muscarinic acetylcholine receptor σ1 σ2
Amineptine >100,00010,0001,000–1,400>100,00074,000NDNDND>100,000>100,000>100,000≥13,000ND>100,000NDND
Amitriptyline 2.8–4.319–353,250≥45018–234.065–14193–1234.4–24114–690196–1,4600.5–1.1669.6300ND
Amoxapine 58164,310ND0.52.06.0–5041502,6003.6–1607.9–25ND1,000NDND
Butriptyline ≥1,3605,1003,9407,000380NDNDND5704,800ND1.1ND35NDND
Clomipramine 0.14–0.2838–54≥2,190≥7,00027–3665541273.2–38≥53578–19013–3120937546ND
Desipramine 18–1630.63–3.53,190≥6,400115–350244–748ND>1,00023–130≥1,3793,40060–1101,55066–198≥1,990≥1,610
Dibenzepin NDND>10,000>10,000≥1,500NDNDND>10,000>10,000>10,000231,9501,750NDND
Dosulepin 8.6–7846–705,3104,000152NDNDND4192,400ND3.6–4.0ND25–26NDND
Doxepin 68–21013–58≥4,60027611–278.8–200136ND2428–1,2703600.09–1.2317423–80NDND
Imipramine 1.3–1.420–378,500≥5,80080–150120190–209>1,000323,100620–7267.6–3755046332–520327–2,100
Iprindole ≥1,6201,2606,5302,800217–280206NDND2,3008,6006,300100–130200–8,3002,100>10,000ND
Lofepramine 705.4>10,0004,600200NDNDND1002,7002,000245–3604,270672,520ND
Maprotiline 5,80011–121,000ND51122ND50909,400350–6650.79–2.0776570NDND
Norclomipramine 400.452,10019,000130NDNDND1901,8001,200450ND92NDND
Northiaden 192252,5392,623141NDNDND950NDND25ND110NDND
Nortriptyline 15–181.8–4.41,1402945.0–418.5148ND552,0302,5703.0–15646372,000ND
Opipramol ≥2,200≥700≥3,000>10,000120NDNDND2006,100120–3006.04,4703,3000.2–50110
Protriptyline 19.61.412,1003,80070NDNDND1306,6002,3007.2–2539825NDND
Tianeptine >10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000>10,000
Trimipramine 149–2,110≥2,450≥3,7808,00032537NDND24680143–2100.27–1.54158NDND
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. For assay species and references, see the individual drug articles. Most but not all values are for human proteins.

With the exception of the sigma receptors, the TCAs act as antagonists or inverse agonists of the receptors and as inhibitors of the transporters. Tianeptine is included in this list due to it technically being a TCA, but with a vastly different pharmacology.

Therapeutic levels of TCAs are generally in the range of about 100 to 300 ng/mL, or 350 to 1,100 nM. [53] Plasma protein binding is generally 90% or greater. [53]


There are two major groups of TCAs in terms of chemical structure, which most, but not all, TCAs fall into. [54] [55] [56] The groupings are based on the tricyclic ring system. [54] [55] [56] They are the dibenzazepines (imipramine, desipramine, clomipramine, trimipramine, lofepramine) and the dibenzocycloheptadienes (amitriptyline, nortriptyline, protriptyline, butriptyline). [54] [55] Minor TCA groups based on ring system include the dibenzoxepins (doxepin), the dibenzothiepines (dosulepin), and the dibenzoxazepines (amoxapine). [54] [55]

In addition to classification based on the ring system, TCAs can also be usefully grouped based on the number of substitutions of the side chain amine. [56] [57] These groups include the tertiary amines (imipramine, clomipramine, trimipramine, amitriptyline, butriptyline, doxepin, dosulepin) and the secondary amines (desipramine, nortriptyline, protriptyline). [56] [57] Lofepramine is technically a tertiary amine, but acts largely as a prodrug of desipramine, a secondary amine, and hence is more similar in profile to the secondary amines than to the tertiary amines. [57] Amoxapine does not have the TCA side chain and hence is neither a tertiary nor secondary amine, although it is often grouped with the secondary amines due to sharing more in common with them. [58] In 2021, a new method was developed at the Institute for Bioengineering of Catalonia for designing photochromic analogs of tricyclic drugs via (1) isosteric replacement of the two-atom bridge between the aromatic systems with an azo group and (2) opening of the central ring. The authors named the strategy "crypto-azologization". [59]

Society and culture

Recreational use

A very small number of cases involving non-medical use of antidepressants have been reported over the past 30 years. [60] According to the US government classification of psychiatric medications, TCAs are "non-abusable" [61] and generally have low misuse potential. [62] Nonetheless, due to their atypical mechanism of action, amineptine and tianeptine (dopamine reuptake inhibition and μ-opioid receptor agonism, respectively) are the two TCAs with the highest addiction and misuse potential. Several cases of the misuse [63] of amitriptyline alone [64] [65] or together with methadone [63] [66] or in other drug dependent patients [67] [68] and of dosulepin with alcohol [69] or in methadone patients [70] have been reported.

List of TCAs

Those that preferentially inhibit the reuptake of serotonin (by at least 10-fold over norepinephrine) include:

Those that preferentially inhibit the reuptake of norepinephrine (by at least 10-fold over serotonin) include:

Whereas either fairly balanced reuptake inhibitors of serotonin and norepinephrine or unspecified inhibitors include:

And the following are TCAs that act via main mechanisms other than serotonin or norepinephrine reuptake inhibition:


See also

Related Research Articles

An anxiolytic is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.

<span class="mw-page-title-main">Maprotiline</span> Antidepressant

Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary amine. In terms of its chemistry and pharmacology, maprotiline is closely related to such-other secondary-amine TCAs as nortriptyline and protriptyline and has similar effects to them, albeit with more distinct anxiolytic effects. Additionally, whereas protriptyline tends to be somewhat more stimulating and in any case is distinctly more-or-less non-sedating, mild degrees of sedation may be experienced with maprotiline.

<span class="mw-page-title-main">Amitriptyline</span> Tricyclic antidepressant

Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and migraine prevention. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

<span class="mw-page-title-main">Imipramine</span> Antidepressant

Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. Imipramine is taken by mouth.

<span class="mw-page-title-main">Desipramine</span> Antidepressant

Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose.

<span class="mw-page-title-main">Clomipramine</span> Antidepressant

Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most-notably obsessive–compulsive disorder but also many other disorders, including panic disorder, major depressive disorder, trichotilomania, body dysmorphic disorder and chronic pain. It has also been notably used to treat premature ejaculation and the cataplexy associated with narcolepsy.

<span class="mw-page-title-main">Nortriptyline</span> Antidepressant medication

Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is also sometimes used for neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many antidepressants, its use for young people with depression and other psychiatric disorders may be limited due to increased suicidality in the 18–24 population initiating treatment. Nortriptyline is a less preferred treatment for ADHD and stopping smoking. It is taken by mouth.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Trimipramine</span> Antidepressant

Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs, however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.

<span class="mw-page-title-main">Dosulepin</span> Antidepressant

Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects.

<span class="mw-page-title-main">Dibenzepin</span> Chemical compound

Dibenzepin, sold under the brand name Noveril among others, is a tricyclic antidepressant (TCA) used widely throughout Europe for the treatment of depression. It has similar efficacy and effects relative to other TCAs like imipramine but with fewer side effects.

<span class="mw-page-title-main">Butriptyline</span> Atypical tricyclic antidepressant medication

Butriptyline, sold under the brand name Evadyne among others, is a tricyclic antidepressant (TCA) that has been used in the United Kingdom and several other European countries for the treatment of depression but appears to no longer be marketed. Along with trimipramine, iprindole, and amoxapine, it has been described as an "atypical" or "second-generation" TCA due to its relatively late introduction and atypical pharmacology. It was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.

<span class="mw-page-title-main">Lofepramine</span> Chemical compound

Lofepramine, sold under the brand names Gamanil, Lomont, and Tymelyt among others, is a tricyclic antidepressant (TCA) which is used to treat depression. The TCAs are so named as they share the common property of having three rings in their chemical structure. Like most TCAs lofepramine is believed to work in relieving depression by increasing concentrations of the neurotransmitters norepinephrine and serotonin in the synapse, by inhibiting their reuptake. It is usually considered a third-generation TCA, as unlike the first- and second-generation TCAs it is relatively safe in overdose and has milder and less frequent side effects.

<span class="mw-page-title-main">Iprindole</span> Atypical tricyclic antidepressant

Iprindole, sold under the brand names Prondol, Galatur, and Tertran, is an atypical tricyclic antidepressant (TCA) that has been used in the United Kingdom and Ireland for the treatment of depression but appears to no longer be marketed. It was developed by Wyeth and was marketed in 1967. The drug has been described by some as the first "second-generation" antidepressant to be introduced. However, it was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.

<span class="mw-page-title-main">Opipramol</span> Drug used to treat depressive and anxiety disorders

Opipramol, sold under the brand name Insidon among others, is an anxiolytic and tricyclic antidepressant that is used throughout Europe. Despite chemically being a tricyclic dibenzazepine (iminostilbene) derivative similar to imipramine, opipramol is not a monoamine reuptake inhibitor like most other tricyclic antidepressants, and instead, uniquely among antidepressants, acts primarily as a SIGMAR1 agonist. It was developed by Schindler and Blattner in 1961.

<span class="mw-page-title-main">Quinupramine</span> Tricyclic antidepressant

Quinupramine is a tricyclic antidepressant (TCA) used in Europe for the treatment of depression.

<span class="mw-page-title-main">Metapramine</span> Chemical compound

Metapramine is a tricyclic antidepressant (TCA) developed by Rhone Poulenc that was introduced for the treatment of depression in France in 1984. In addition to its efficacy against affective disorders, it also has analgesic properties, and may be useful in the treatment of pain.

<span class="mw-page-title-main">Amitriptylinoxide</span> Chemical compound

Amitriptylinoxide, or amitriptyline N-oxide, is a tricyclic antidepressant (TCA) which was introduced in Europe in the 1970s for the treatment of depression.

<span class="mw-page-title-main">Imipraminoxide</span> Chemical compound

Imipraminoxide, or imipramine N-oxide, is a tricyclic antidepressant (TCA) that was introduced in Europe in the 1960s for the treatment of depression.


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