Patat A, Naef M M, van Gessel E, Forster A, Dubruc C, Rosenzweig P
Clinical Research Department, Synthelabo Recherche, Bagneux.
Clin Pharmacol Ther. 1994 Oct;56(4):430-6. doi: 10.1038/clpt.1994.157.
Zolpidem is a new imidazopyridine-hypnotic that selectively binds to the central omega 1-receptor subtype. A double-blind, randomized, three-way, crossover placebo-controlled study was carried out in nine healthy male volunteers to assess the possible antagonism of central nervous system--depressant effects of zolpidem by flumazenil. Subjects received zolpidem (0.21 mg/kg) or placebo, intravenously, followed 17 minutes later by flumazenil (0.04 mg/kg) or placebo. Vigilance and performance were assessed by a trained anesthetist with use of ciliary reflex, response to a verbal instruction, subjective sedation, a tracking task, and a free recall task. Zolpidem produced a clinically relevant hypnotic effect in five subjects and significantly impaired performance in all nine subjects up to 90 minutes after dosing. Flumazenil rapidly antagonized clinical sedation in the five subjects who were asleep and significantly reversed the performance decrement within 3 minutes, without any escape phenomenon. Flumazenil did not change zolpidem plasma concentrations, confirming the pharmacodynamic nature of the interaction. Flumazenil may thus be a safe and effective antidote in patients with zolpidem overdosage.
唑吡坦是一种新型咪唑吡啶类催眠药，它能选择性地与中枢ω1受体亚型结合。在9名健康男性志愿者中进行了一项双盲、随机、三向交叉、安慰剂对照研究，以评估氟马西尼对唑吡坦中枢神经系统抑制作用的可能拮抗作用。受试者静脉注射唑吡坦（0.21mg/kg）或安慰剂，17分钟后再静脉注射氟马西尼（0.04mg/kg）或安慰剂。由一名训练有素的麻醉师通过睫状反射、对口头指令的反应、主观镇静、跟踪任务和自由回忆任务来评估警觉性和表现。唑吡坦在5名受试者中产生了具有临床意义的催眠效果，并且在给药后长达90分钟内，所有9名受试者的表现均受到显著损害。氟马西尼迅速拮抗了5名入睡受试者的临床镇静作用，并在3分钟内显著逆转了表现下降，且没有任何逃逸现象。氟马西尼并未改变唑吡坦的血浆浓度，证实了这种相互作用的药效学性质。因此，氟马西尼可能是治疗唑吡坦过量患者的一种安全有效的解毒剂。
