Gerak L R, Woolverton W L, Nader M A, Patrick G A, Harris L S, Winger G, Woods J H, France C P
Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Drug Alcohol Depend. 2001 Jun 1;63(1):39-49. doi: 10.1016/s0376-8716(00)00189-7.
Flunitrazepam was evaluated in several procedures that have been used extensively to study the behavioral effects and abuse potential of positive GABA(A) modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i.v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimination studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of flunitrazepam is comparable to that of other benzodiazepines.
氟硝西泮在几种已被广泛用于研究正向γ-氨基丁酸A（GABA(A)）调节剂的行为效应和滥用潜力的实验程序中进行了评估。一组猴子（n = 3）通过静脉注射甲己炔巴比妥或生理盐水来做出反应，而其他组（每组n = 2 - 4）对戊巴比妥或三唑仑与溶媒进行辨别。另外的猴子（n = 2）每天接受地西泮治疗，并对氟马西尼与溶媒进行辨别。最后，评估了氟硝西泮预防戊巴比妥治疗的大鼠出现戒断症状的能力。氟硝西泮维持的静脉自我给药，平均而言，低于甲己炔巴比妥维持的水平，高于生理盐水维持的水平。在药物辨别研究中，氟硝西泮替代了戊巴比妥和三唑仑，但未能替代氟马西尼。在大鼠（每组n = 3 - 6）中，当用氟硝西泮治疗替代戊巴比妥治疗时，未出现明显的戒断症状；当戊巴比妥或氟硝西泮治疗终止时，出现了戒断症状。结合先前研究的数据，这些数据表明氟硝西泮的滥用可能性与其他苯二氮䓬类药物相当。
