氨己烯酸的作用机制及代谢分布研究进展

Research progress of the mechanism,metabolism and distribution of vigabatrin

抗癫痫药物氨己烯酸(vigabatrin,VGB)是一种选择性、不可逆的γ-氨基丁酸转氨酶抑制剂,可通过增加中枢神经系统抑制性神经递质γ-氨基丁酸的浓度抑制大脑神经元异常放电。VGB的临床适应证为婴儿痉挛症的单一治疗、难治性部分发作性癫痫的辅助治疗,导致视野损失是限制其临床使用的主要不良反应。研究表明,除调节γ-氨基丁酸能神经功能之外,VGB还可通过调节β-丙氨酸、天冬氨酸和鸟氨酸等组织内源性物质的代谢变化及雷帕霉素机械靶蛋白(mTOR)信号通路的功能等途径发挥其抗癫痫作用。本文主要就VGB的作用机制及其体内代谢分布研究进展进行综述,旨在为深入了解VGB的药效和毒副作用机制提供依据。

The antiepileptic drug vigabatrin(VGB) is a selective and irreversible inhibitor of γ-aminobutyric acid transaminase,which can inhibit the abnormal electrical activity in brain via increasing the concentration of inhibitory neurotransmitter γ-aminobutyric acid(GABA).The clinical indications of VGB include infantile spasms and refractory partial seizure epilepsy,acting as a single treatment or an adjuvant treatment,respectively.Visual field loss is the main adverse reaction of VGB that limits its clinical application.Increasing evidence has demonstrated that,apart from acting on the GABA ergic system,VGB exerts an antiepileptic effect via regulating the metabolic changes of tissue endogenous substances including β-alanine,aspartic acid,ornithine,as well as the function of mechanistic target of rapamycin(mTOR) signalling pathway.In this article,we mainly review the progress of the studies focusing on mechanism,metabolism,and distribution of VGB,which will be helpful to understand the pharmacodynamics and toxic and side effects of VGB in depth.