Targets for antiepileptic drugs in the synapse.
Targets for antiepileptic drugs in the synapse.
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发表时间：
2006-12
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通讯作者：
C. J. Landmark
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作者：
C. J. Landmark
抗癫痫药物（AEDs）有许多已提出的作用机制，但仍未完全了解。目前，AED被广泛用于治疗癫痫、偏头痛、神经性疼痛和双相情感障碍，其他疾病也正在研究中。本文综述了抗癫痫药物作用于GABA能和GABA能突触的主要靶点，以及抗癫痫药物未来可能的作用部位，以阐明抗癫痫药物的广谱活性。这项研究是对最近发表的关于抗癫痫药物作用机制的研究的综述。AED在突触中的主要作用靶点包括增强GABA能抑制性神经传递、直接或通过抑制电压依赖性钠和钙通道减少多巴胺能兴奋性神经传递以及干扰细胞内信号通路。氨己烯酸、噻加宾和丙戊酸盐主要作用于GABA能突触。左乙拉西坦、托吡酯、拉莫三嗪、卡马西平、奥卡西平、加巴喷丁、普瑞巴林、非氨酯和唑尼沙胺可降低多巴胺能兴奋性。此外，丙戊酸盐、卡马西平和奥卡西平可调节细胞内信号通路。几种基于现有药物的新一代AED正在开发中。未来降低兴奋性的靶点可能包括GABA和谷氨酸离子型和代谢型受体以及星形胶质细胞。了解AEDs在突触中的作用部位对于提高我们对其广泛临床疗效的理解以及开发未来治疗癫痫和其他神经和精神疾病的有效药物非常重要。
Antiepileptic drugs (AEDs) have many proposed mechanisms of action and are still not fully understood. AEDs are widely used today to treat epilepsy, migraine, neuropathic pain, and bipolar disorder, and other disorders are also being investigated. The focus in this review is the main targets for AEDs in the GABAergic and glutamatergic synapses and possible future sites of action for AEDs to clarify their wide spectrum of activity. The study is a review of recently published investigations of the mechanisms of action of AEDs. The main targets for AEDs in the synapses include enhancement of GABAergic inhibitory neurotransmission, decrease in glutamatergic excitatory neurotransmission directly or via inhibition of voltage-dependent sodium and calcium channels, and interference with intracellular signaling pathways. Vigabatrin, tiagabine, and valproate possess their main actions in the GABAergic synapse. Levetiracetam, topiramate, lamotrigine, carbamazepine, oxcarbazepine, gabapentin, pregabalin, felbamate, and zonisamide decrease glutamatergic excitability. In addition, valproate, carbamazepine, and oxcarbazepine modulate intracellular signaling pathways. Several AEDs of a new generation based on the existing drugs are in development. Future targets to decrease excitability may include GABA and glutamate ionotropic and metabotropic receptors and astrocytes. Knowledge of the sites of action of AEDs in the synapse is important to improve our understanding of their broad spectrum of clinical efficacy and to develop future effective drugs for the treatment of both epilepsy and other neurological and psychiatric disorders.