Richens A, Chadwick D W, Duncan J S, Dam M, Gram L, Mikkelsen M, Morrow J, Mengel H, Shu V, McKelvy J F
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, UK.
Epilepsy Res. 1995 May;21(1):37-42. doi: 10.1016/0920-1211(95)00006-v.
Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into neurons and glia. A double-blind, placebo-controlled, crossover trial was undertaken, based upon a response-dependent design. Ninety-four patients with complex partial seizures with or without secondary generalised tonic-clonic seizures were recruited into an open screening phase and tiagabine was added to their existing drug therapy in doses titrated to reduce seizure frequency by > or = 25% or to the limit of tolerance. Forty-six responders were subsequently randomised to a double-blind crossover trial in which tiagabine was compared with placebo. Forty-two patients completed the trial. A significant reduction in the frequency of complex partial and secondary generalised tonic clonic seizures was seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their complex partial seizures, and of the 27 patients who also had secondary generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No interactions with baseline antiepileptic drugs were detected and no serious adverse reactions occurred. The commonest adverse events were tiredness, dizziness and headache. We conclude that tiagabine has promising antiepileptic effects. Further trials are underway.
噻加宾是一种新型抗癫痫药物，其作用机制新颖，可抑制抑制性神经递质γ-氨基丁酸（GABA）再摄取进入神经元和神经胶质细胞。基于反应依赖性设计进行了一项双盲、安慰剂对照的交叉试验。94例伴有或不伴有继发性全身强直阵挛发作的复杂部分性发作患者进入开放筛选阶段，噻加宾以滴定剂量添加到他们现有的药物治疗中，以将癫痫发作频率降低≥25%或达到耐受极限。46例有反应者随后被随机分配到一项双盲交叉试验中，将噻加宾与安慰剂进行比较。42例患者完成了试验。观察到复杂部分性发作和继发性全身强直阵挛发作的频率显著降低。26%的患者复杂部分性发作频率降低≥50%，在27例也有继发性全身强直阵挛发作的患者中，63%的患者发作频率降低≥50%。未检测到与基线抗癫痫药物的相互作用，也未发生严重不良反应。最常见的不良事件是疲劳、头晕和头痛。我们得出结论，噻加宾具有有前景的抗癫痫作用。进一步的试验正在进行中。
