|Oral, IM, IV|
|Biological half-life||23-24 hours|
|Chemical and physical data|
|Molar mass||294.434 g/mol|
|3D model (Jmol)|
Trimipramine's primary use in medicine is in the treatment of major depressive disorder, especially where sedation is required due to its prominent sedative effects. Trimipramine also has some weak antipsychotic effects which are less pronounced than with the phenothiazine antipsychotic perazine.
Trimipramine is the only effective drug against insomnia known so far that does not alter the normal sleep architecture (there is evidence in medical journals that refute this last statement[weasel words]). In particular, it does not suppress REM sleep, and dreams are said to brighten during treatment.
Note: Bolded adverse effects are serious ones.
- Sedation — especially common with trimipramine compared to the other TCAs
- Anticholinergic effects including:
- - dry mouth
- - blurred vision
- - mydriasis
- - decreased lacrimation
- - constipation
- - urinary hesitancy or retention
- - reduced GI motility
- - tachycardia (high heart rate)
- - anticholinergic delirium (particularly in the elderly and in Parkinson's disease)
- Weight gain
- Orthostatic hypotension
- Sexual dysfunction including impotence, loss of libido and other sexual adverse effects
- Extrapyramidal side effects (e.g. parkinsonism, dystonia, etc.)
- ECG changes
- Increased liver function tests
- Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
- Blood dyscrasias including:
- Myocardial infarction
- Heart block
- QTc interval prolongation
- Sudden cardiac death
- Depression worsening
- Suicidal ideation
- Recent myocardial infarction
- Any degree of heart block or other cardiac arrhythmias
- Severe liver disease
- During breast feeding
- Hypersensitivity to trimipramine maleate or to any of the excipients
Compared to other tricyclic antidepressants trimipramine is relatively safe in overdose, although it is more dangerous than the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) but less dangerous than bupropion in cases of overdose.
Mechanism of action
Trimipramine's mechanism of action differs from other TCAs. It is a weak to moderate reuptake inhibitor of serotonin, and an extremely weak inhibitor of norepinephrine and dopamine reuptake. Its main effects are due to considerable receptor antagonism as follows:
Trimipramine is a racemic compound with two enantiomers. CYP2C19 is responsible for the demethylation of (D)- and (L)-trimipramine to (D)- (L)-desmethyltrimipramine, respectively, and CYP2D6 is responsible for the 2-hydroxylation of (D)- and (L)-desmethyltrimipramine to (D)- and (L)-2-hydroxydesmethyltrimipramine, respectively. CYP2D6 also metabolizes (L)-trimipramine into (L)-2-hydroxytrimipramine.
Trimipramine maleate (as Surmontil) oral capsules were first approved by the Food and Drug Administration prior to January 1, 1982 in 25 mg and 50 mg formulations, with the 100 mg formulation having been approved on September 15, 1982. A generic version of all three formulations was given FDA approval on August 2, 2006.
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