Gerra G, Giucasto G, Zaimovic A, Fertonani G, Chittolini B, Avanzini P, Caccavari R, Delsignore R
Centro Studi Farmacotossicodipendenze, SER.T., AUSL Parma, Italy.
Int Clin Psychopharmacol. 1996 Jun;11(2):81-8.
The capacity of flumazenil to reverse benzodiazepine agonist effects has been widely demonstrated. In contrast, the role of flumazenil in precipitating withdrawal symptoms is unclear in humans: the inability of RO 15-1788 to induce benzodiazepine withdrawal seems to be related to the duration of exposure to the GABAergic drugs. In the present experiment we evaluated the effects of intravenous flumazenil or placebo in 36 healthy volunteers pretreated with lormetazepam for 30 days (2 mg/day) and 18 lormetazepam-dependent subjects (6-8 mg/day). Measurements of a balance task, subject- and observer-rated symptoms showed a reversal of lormetazepam effects induced by flumazenil without any significant withdrawal symptoms. Slight anxiety, increase in heart rate and perspiration were observed in a few subjects. Independent of benzodiazepine doses, long-term treatment seems to be responsible for tolerance development with consistent changes in GABA-benzodiazepine receptor sensitivity. Flumazenil could be able to normalize benzodiazepine receptor sensitivity and exert its weak agonist activity.
氟马西尼逆转苯二氮䓬激动剂作用的能力已得到广泛证实。相比之下，氟马西尼在引发戒断症状方面在人类中的作用尚不清楚：RO 15 - 1788无法诱发苯二氮䓬戒断似乎与接触GABA能药物的持续时间有关。在本实验中，我们评估了静脉注射氟马西尼或安慰剂对36名用氯美扎酮预处理30天（2毫克/天）的健康志愿者和18名氯美扎酮依赖者（6 - 8毫克/天）的影响。平衡任务测量、受试者和观察者评定的症状显示氟马西尼可逆转氯美扎酮的作用，且无任何明显的戒断症状。少数受试者出现轻微焦虑、心率加快和出汗。与苯二氮䓬剂量无关，长期治疗似乎是耐受性发展的原因，同时GABA - 苯二氮䓬受体敏感性也发生了持续变化。氟马西尼可能能够使苯二氮䓬受体敏感性恢复正常并发挥其弱激动剂活性。
