Тримипрамин

Использование

Antidepressant.

Определение

ChEBI: A dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)-2-methylpropyl group at the nitrogen atom. It is used as an antidepressant.

Всемирная организация здравоохранения(ВОЗ)

Trimipramine, a tricyclic antidepressant was introduced in 1961 for the management of endogenous depression. Much of the adverse effects are caused by its antimuscarinic actions. These include dry mouth, cardiac arrhythmias, central nervous system disturbances, blood disorders and risk of suicide. The risk of suicide and dangers related to overdosage led Norwegian Medicines Control Authority to put the higher strength formulation under prescribing restriction in 1992. The risk of death following overdosage is apparently higher for products containing tricyclic compounds as compared with nontricyclic products.

Фармакокине?тика

Trimipramine is one of the antidepressants with the most pronounced differences in pharmacokinetics caused by the CYP2D6 genetic polymorphism. Its bioavailability and systemic clearance depended significantly on the CYP2D6 isoform with a linear dose relationship. Its mean bioavailability was 44% in individuals without CYP2D6 (poor metabolizers) but 16 and 12% in those individuals with two and three active genes of CYP2D6 (fast and ultrafast metabolizers), respectively. Consequently, the mean total clearances of the oral dose were 27, 151, and 253 L/hour in poor, extensive, and ultrarapid metabolizers, respectively. The 44% bioavailability combined with low systemic clearance of trimipramine in poor metabolizers of CYP2D6 substrates results in a very high exposure to trimipramine with the risk of adverse drug reactions. On the other hand, the presystemic elimination may result in subtherapeutic drug concentrations in carriers of CYP2D6 gene duplications with a high risk of poor therapeutic response

Клиническое использование

Although trimipramine has the weakest binding affinity for the monoamine transporters, it shares the pharmacological and toxicity actions of the other TCAs and is used primarily in the treatment of depression.