Кломипрамин

Использование

Antidepressan.

Определение

ChEBI: A dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine which is substituted by chlorine at position 3 and in which the hydrogen attached to the nitrogen is replaced by a 3-(dimethylamino)propyl group. One of the more sedating tricyclic antidepressan s, it is used as the hydrochloride salt for the treatment of depression as well as obsessive-compulsive disorder and phobias.

Механизм действия

Clomipramine is different from the other TCAs, exhibiting preferential selectivity for inhibiting the reuptake of 5-HT at the presynaptic neuronal membrane. Its antidepressant mechanism of action as an inhibitor of the 5-HT transporter is reduced in vivo, however, because of the formation of its active metabolite, N-desmethylclomipramine, which inhibits the reuptake of NE. As a result of its common structure with the other TCAs, clomipramine shares the pharmacological and adverse-effect profile of the other TCAs.
The efficacy of clomipramine relative to the other TCAs in the treatment of obsessive-compulsive disorder may be related to its potency in blocking 5-HT reuptake at the presynaptic neuronal membrane, suggesting a dysregulation of 5-HT for the pathogenesis of obsessive-compulsive disorder. Clomipramine appears to decrease the turnover of 5-HT in the CNS, probably because of a decrease in the release and/or synthesis of 5-HT.
Although in vitro studies suggest that clomipramine is approximately four times more potent than fluoxetine as a 5-HT reuptake inhibitor, in vivo studies suggest the opposite. This difference has been attributed to the relatively long elimination half-lives for fluoxetine and its principal serotonergic metabolite norfluoxetine. In addition, metabolism of clomipramine to its N-desmethyl secondary amine metabolite decreases the potency and selectivity of 5-HT -reuptake inhibition of clomipramine, but not fluoxetine.

Клиническое использование

Clomipramine is considered to be the most powerful antidepressant ever made. This dihydrodibenzazepine TCA, with actions on both the NE and 5-HT transporters, was the last of the major TCAs to come to market. Initially, the U.S. FDA regarded it as another “me-too” drug, and accordingly, they did not license it. Subsequently, however, it was licensed for the treatment of obsessive-compulsive disorders. Clomipramine differs from imipramine only by the addition of a 3-chloro group.

Побочные эффекты

Male patients taking clomipramine should be informed of sexual dysfunction as a side effect associated with antidepressants having significant serotonergic activity. Sexual dysfunction in men appears as ejaculatory incompetence, ejaculatory retardation, decreased libido, or inability to obtain or maintain an erection. Sexual dysfunction is dose-related and may be treated by simply lowering the drug dose.