クロミプラミン 化学特性,用途語,生産方法
効能
抗うつ薬, セロトニン・ノルアドレナリン再取り込み阻害薬
使用
Antidepressan.
定義
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.
作用機序
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.
臨床応用
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.
副作用
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.
クロミプラミン 上流と下流の製品情報
原材料
準備製品