Davies J A
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Seizure. 1995 Dec;4(4):267-71. doi: 10.1016/s1059-1311(95)80003-4.
Depending on their mechanism of action, anticonvulsant drugs in clinical use may be divided into three groups: those drugs which facilitate gamma-aminobutryic acid (GABA)ergic neurotransmission; those which block neuronal ion channels; and those whose mechanism of action is unresolved. The compounds acting on GABAergic systems may be further subdivided into those which modulate transmission through chloride channels, e.g. the barbiturates and the benzodiazepines; those compounds, in particular vigabatrin, which reduce the degradation of GABA by blocking GABA transaminase; and those which inhibit the re-uptake of GABA into the presynaptic terminal. The other group of compounds whose mechanism of action is known are those which block neuronal ion channels. Blockage of voltage-operated sodium channels by lamotrigine, phenytoin or carbamazepine leads to decreased electrical activity and, probably, a subsequent reduction in glutamate release. Conversely, ethosuximide, blocks voltage-operated calcium channels, especially those which mediate calcium currents in thalamic neurones. Of those drugs in which the mechanism of action is unknown, sodium valproate is the prime example. An antagonistic action at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor might also be a possibility, which could be the case with some of the newer compounds currently undergoing evaluation.
根据其作用机制，临床使用的抗惊厥药物可分为三类：一类是促进γ-氨基丁酸（GABA）能神经传递的药物；一类是阻断神经元离子通道的药物；还有一类其作用机制尚未明确。作用于GABA能系统的化合物可进一步细分为：通过氯离子通道调节神经传递的化合物，如巴比妥类和苯二氮䓬类；通过阻断GABA转氨酶来减少GABA降解的化合物，特别是氨己烯酸；以及抑制GABA再摄取到突触前终末的化合物。另一类作用机制已知的化合物是阻断神经元离子通道的药物。拉莫三嗪、苯妥英或卡马西平对电压门控钠通道的阻断会导致电活动降低，并且可能随后减少谷氨酸释放。相反，乙琥胺阻断电压门控钙通道，尤其是介导丘脑神经元钙电流的通道。在作用机制未知的药物中，丙戊酸钠是主要例子。对谷氨酸受体N-甲基-D-天冬氨酸（NMDA）亚型的拮抗作用也有可能，目前正在评估的一些新化合物可能就是这种情况。
