Department of Pharmacology, School of Medicine, University of South Carolina, Columbia, South Carolina 29208, USA.
Epilepsia. 2011 Apr;52 Suppl 2(0 2):76-8. doi: 10.1111/j.1528-1167.2011.03008.x.
The anticonvulsant stiripentol (Diacomittm) has been shown to have a positive impact on control of seizures for many patients with Dravet syndrome. As with most antiepileptic drugs, stiripentol has multiple mechanisms of action. Its direct anticonvulsant activity is likely due to enhancement of inhibitory, γ-aminobutyric acid (GABA)ergic neurotransmission. Stiripentol was shown to increase the activity of both neuronal and recombinant GABA(A) receptors at clinically relevant concentrations. At recombinant receptors, stiripentol was found to act through a unique site in a subunit-dependent manner. Positive modulation by stiripentol was most effective at GABA(A) receptors containing an α3 subunit. The expression of the α3 subunit is developmentally regulated, with highest levels in the immature brain. This subunit selectivity may explain the greater clinical efficacy of stiripentol in childhood-onset epilepsies, including Dravet syndrome.
抗惊厥药物屈昔多巴（Diacomittm）已被证明对许多患有德拉维特综合征的患者的癫痫发作控制具有积极影响。与大多数抗癫痫药物一样，屈昔多巴具有多种作用机制。其直接的抗惊厥活性可能是由于增强了抑制性γ-氨基丁酸（GABA）能神经传递。屈昔多巴在临床相关浓度下显示出增加神经元和重组 GABA(A)受体的活性。在重组受体中，发现屈昔多巴以亚单位依赖性的方式通过独特的位点起作用。屈昔多巴的正调节在含有α3 亚单位的 GABA(A)受体中最有效。α3 亚单位的表达受发育调控，在未成熟的大脑中水平最高。这种亚单位选择性可能解释了屈昔多巴在儿童期起病的癫痫，包括德拉维特综合征中的临床疗效更高。
