Wesensten N J, Balkin T J, Davis H Q, Belenky G L
Department of Behavioral Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Psychopharmacology (Berl). 1995 Sep;121(2):242-9. doi: 10.1007/BF02245635.
The effects of flumazenil, a benzodiazepine receptor antagonist, on triazolam- and zolpidem-induced memory impairment were investigated. Sixty subjects received oral triazolam 0.5 mg, zolpidem 20.0 mg, or placebo at 10 a.m. (n = 20 per drug). Ninety minutes later, half of the subjects (n = 10) in each oral drug group were administered flumazenil 1.0 mg, while the remaining half received placebo (normal saline), through indwelling venous catheters. Learning/memory tests (including Simulated Escape, Restricted Reminding, Paired-Associates, and Repeated Acquisition) were administered at that time, and at 1.5-h intervals over the next 6 h. Triazolam/placebo and zolpidem/placebo drug combinations impaired memory on all tests (all Ps < 0.05). However, the triazolam/flumazenil and zolpidem/flumazenil groups showed no evidence of impairment during any test session. These results demonstrate that flumazenil 1.0 mg rapidly and lastingly reverses memory impairment caused by agonists of the benzodiazepine receptor. Furthermore, nonsignificant trends suggested that performance of the placebo/flumazenil group was consistently better than that of the placebo/placebo group, denoting a possible role of endogenous benzodiazepine agonists in natural sleep/wake processes.
研究了苯二氮䓬受体拮抗剂氟马西尼对三唑仑和唑吡坦所致记忆损害的影响。60名受试者于上午10点口服0.5毫克三唑仑、20.0毫克唑吡坦或安慰剂（每种药物n = 20）。90分钟后，每个口服药物组中的一半受试者（n = 10）通过留置静脉导管给予1.0毫克氟马西尼，而其余一半受试者接受安慰剂（生理盐水）。此时以及在接下来的6小时内每隔1.5小时进行学习/记忆测试（包括模拟逃脱、限制性回忆、配对联想和重复习得）。三唑仑/安慰剂和唑吡坦/安慰剂药物组合在所有测试中均损害记忆（所有P < 0.05）。然而，三唑仑/氟马西尼组和唑吡坦/氟马西尼组在任何测试期间均未显示出损害的迹象。这些结果表明，1.0毫克氟马西尼可迅速且持久地逆转苯二氮䓬受体激动剂所致的记忆损害。此外，无显著差异的趋势表明，安慰剂/氟马西尼组的表现始终优于安慰剂/安慰剂组，这表明内源性苯二氮䓬激动剂在自然睡眠/觉醒过程中可能发挥作用。
