Department of Human Anatomy, Medical University, Jaczewskiego 4, PL 20-090 Lublin, Poland.
Pharmacol Rep. 2010 Mar-Apr;62(2):211-9. doi: 10.1016/s1734-1140(10)70260-7.
Retigabine represents an antiepileptic drug possessing a completely different mechanism of action when compared to the existing classical and newer antiepileptic drugs. In the therapeutic range, retigabine enhances potassium currents, very likely via destabilization of a closed conformation or stabilization of the open conformation of the potassium Kv7.2-7.3 channels. There are also data indicating that this drug may be a GABA enhancer. Kainate-induced status epilepticus in rats resulted in massive apoptosis in the pyriform cortex and hippocampal area - retigabine inhibited neurodegeneration only in the former brain structure. The metabolism of retigabine has nothing to do with cytochrome P450 enzymes and the drug undergoes glucuronidation and acetylation. Randomized, placebo-controlled multicenter studies have shown that retigabine produced a considerable improvement as an add-on drug in patients with partial drug-resistant epilepsy. The most prominent adverse effects due to retigabine combined with the existing antiepileptic treatment were dizziness, somnolence and fatigue. The preclinical data indicate that this antiepileptic drug may possibly be applied in patients with neuropathic pain and affective disorders. Initial clinical data suggest that retigabine may be also effective in Alzheimer's disease or stroke.
雷替加滨是一种抗癫痫药物，与现有的经典和新型抗癫痫药物相比，具有完全不同的作用机制。在治疗范围内，雷替加滨增强钾电流，很可能通过使钾 Kv7.2-7.3 通道的关闭构象不稳定或开放构象稳定来实现。也有数据表明，这种药物可能是 GABA 增强剂。在大鼠中，红藻氨酸诱导的癫痫持续状态导致梨状皮层和海马区大量细胞凋亡——雷替加滨仅抑制前一种脑结构的神经退行性变。雷替加滨的代谢与细胞色素 P450 酶无关，药物经历葡萄糖醛酸化和乙酰化。随机、安慰剂对照的多中心研究表明，雷替加滨作为附加药物在部分耐药性癫痫患者中产生了显著的改善。由于雷替加滨联合现有抗癫痫治疗最突出的不良反应是头晕、嗜睡和疲劳。临床前数据表明，这种抗癫痫药物可能适用于治疗神经性疼痛和情感障碍患者。初步临床数据表明，雷替加滨对阿尔茨海默病或中风也可能有效。
