莫达非尼的促觉醒作用和药动学

Wake-promoting action and pharmacokinetics of modafinil

莫达非尼(modafinil)是一种强效促觉醒药。它的促觉醒作用依赖于多巴胺(DA)能神经的激活,也与抑制γ-氨基丁酸(GABA)的释放和促进谷氨酸释放有关,完整的儿茶酚胺(包括DA)系统和5-羟色胺(5-HT)系统对莫达非尼抑制GABA的释放是必须的。莫达非尼还可能通过激活orexin(食欲素)神经元促进组胺释放而增加自发活动,部分与它的促觉醒作用有关。莫达非尼口服迅速吸收,在肝脏代谢,失活代谢产物和少于10%的原型药物从尿排泄。

Modafinil is a potent wake-promoting agent.Its actions are dependent on the activation of dopaminergic nerve and related to decrease of γ-aminobutyric acid（GABA）release and increase of glutamate release.Intact catecholamine（including dopamine）and serotonin systems are essential for modafinil effects on GABA.An increase in the release of histamine induced by an activation of modafinil on orexin neurons seems also to be related to an increase of the locomotion activity which is partially involved in its wakefulness.Modafinil is readily absorbed after oral administration.The liver is the primary site of metabolism.The inactive metabolites and less than 10% uncharged drug are excreted by kidney.