Bryans J S, Wustrow D J
Parke-Davis Neuroscience Research Center, Forvie Site, Cambridge, UK.
Med Res Rev. 1999 Mar;19(2):149-77. doi: 10.1002/(sici)1098-1128(199903)19:2<149::aid-med3>3.0.co;2-b.
Gabapentin and Pregabalin are both 3-alkylated gamma-amino butyric acid (GABA) analogs. Gabapentin was designed as a lipophilic GABA analog and was first synthesized as a potential anticonvulsant and was launched in 1994 as add-on therapy for the treatment of epilepsy. In this review the discovery and development of gabapentin as an anticonvulsant are discussed. During human trials and while in clinical use, it became apparent that gabapentin induced some other potentially useful therapeutic effects in chronic pain states and behavioral disorders. A review of animal and clinical data relating to these other potential therapeutic utilities is presented. Pregabalin was identified after an investigation into other 3-substituted GABA analogs. It has since been shown to have a similar pharmacological profile to gabapentin with greater potency in preclinical models of pain and epilepsy. Studies of the mechanism(s) of action of these compounds are discussed. Work towards identifying new analogs of both gabapentin and pregabalin is also reviewed.
加巴喷丁和普瑞巴林都是3-烷基化γ-氨基丁酸（GABA）类似物。加巴喷丁被设计为一种亲脂性GABA类似物，最初作为一种潜在的抗惊厥药合成，并于1994年作为癫痫附加疗法推出。在本综述中，将讨论加巴喷丁作为抗惊厥药的发现和开发过程。在人体试验期间以及临床使用过程中，加巴喷丁在慢性疼痛状态和行为障碍中诱导出一些其他潜在有用的治疗效果这一点变得很明显。本文将对与这些其他潜在治疗用途相关的动物和临床数据进行综述。普瑞巴林是在对其他3-取代GABA类似物进行研究后确定的。此后已证明它具有与加巴喷丁相似的药理学特征，在疼痛和癫痫的临床前模型中效力更强。本文还将讨论这些化合物作用机制的研究。同时也会综述寻找加巴喷丁和普瑞巴林新类似物的工作进展。
