Trimipramine is an tricyclic antidepressant with sedative and anxiolytic properties.

Pharmacology

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Trimipramine's mechanism of action differs from other tricyclic antidepressants. It is only a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamin. The main effects are due to considerable postynaptic blockade as follows:

• strong : 5-HT2, Muscarinic, H1, H2, Alpha1
• moderate : D2
• weak : 5-HT1, Alpha2

The spectrum of effects (strong antidepressant activity, sedation and anxiolysis) and side-effects (strong anticholinergic and antiadrenergic side-effcts) is the same as with Doxepin. It is also a more effective sedative than Amitriptyline. Trimipramine is the only effective drug against insomnia known so far that does not alter the normal sleep architecture. In particular, it does not suppress REM-sleep. Moreover, dreams are said to brighten during treatment. Its relatively strong antagonistic activity at postsynaptic D2-receptors led to a clinical study trying Trimipramine as atypical neuroleptic. There it exerted good antipsychotic activity with a low incidence of extrapyramidal and other side-effects. But this study encompassed only 28 patients, so the use of Trimipramine as a neuroleptic needs further confirmation and can currently not be recommended. Trimipramine shows also useful activity against chronic pain.

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