Kavoussi Richard
Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.
Eur Neuropsychopharmacol. 2006 Jul;16 Suppl 2:S128-33. doi: 10.1016/j.euroneuro.2006.04.005. Epub 2006 Jun 9.
Pregabalin, a compound with a novel mechanism of action (MOA), has demonstrated efficacy as an adjunctive treatment for epilepsy and in several neuropathic pain models. Multiple generalized anxiety disorder (GAD) clinical trials have shown that pregabalin has efficacy similar to the benzodiazepines and venlafaxine. Onset of anxiolytic effect was observed as early as Week 1 of treatment, and efficacy was seen in treating both psychic and somatic anxiety symptoms. Pregabalin binds potently and selectively to the alpha-2-delta subunit of "hyper-excited" voltage-gated calcium channels (VGCCs). The binding of pregabalin to VGCCs changes their conformation, reducing calcium influx at nerve terminals. Pregabalin only modulates the release of excitatory neurotransmitters in "hyper-excited" neurons, restoring them to normal physiological state. This newly defined MOA is believed to confer on pregabalin its anxiolytic, analgesic, and anticonvulsant properties. Thus, pregabalin may offer physicians an effective and well-tolerated therapy for GAD, which differs from existing treatments.
普瑞巴林是一种具有新型作用机制（MOA）的化合物，已证明其作为癫痫辅助治疗药物以及在多种神经性疼痛模型中具有疗效。多项广泛性焦虑症（GAD）临床试验表明，普瑞巴林的疗效与苯二氮䓬类药物和文拉法辛相似。早在治疗第1周就观察到抗焦虑作用起效，并且在治疗精神性和躯体性焦虑症状方面均有疗效。普瑞巴林强效且选择性地结合“过度兴奋”的电压门控钙通道（VGCCs）的α-2-δ亚基。普瑞巴林与VGCCs的结合改变其构象，减少神经末梢的钙内流。普瑞巴林仅调节“过度兴奋”神经元中兴奋性神经递质的释放，使其恢复到正常生理状态。这种新定义的作用机制被认为赋予了普瑞巴林抗焦虑、镇痛和抗惊厥特性。因此，普瑞巴林可能为医生提供一种针对GAD的有效且耐受性良好的治疗方法，这与现有治疗方法不同。
