Chan A W, Leong F W, Schanley D L, Langan M C, Penetrante F
Research Institute on Alcoholism, New York State Division of Alcoholism and Alcohol Abuse, Buffalo 14203.
Pharmacol Biochem Behav. 1991 Jul;39(3):659-63. doi: 10.1016/0091-3057(91)90143-p.
There are conflicting reports concerning whether flumazenil (Ro15-1788) can antagonize the central effects of ethanol and ethanol withdrawal reactions. C57BL/6J mice were treated chronically with an ethanol liquid diet. Control mice were pair fed an isocaloric diet containing no ethanol. These mice were injected with either Ro15-1788 (25 mg/kg) or vehicle immediately before, 14 h or 24 h before ethanol withdrawal. Under these conditions, no attenuation of the severity of handling-induced withdrawal seizures or of withdrawal hypothermia was observed in the ethanol-dependent mice injected with Ro15-1788. Likewise, there was no abolition or attenuation of tolerance to the ataxic effects (sleep time and horizontal dowel tests) and hypothermic effects of ethanol by Ro15-1788 when the mice were tested on day 3 of ethanol withdrawal. It is concluded that Ro15-1788 (25 mg/kg) has no effect on ethanol tolerance and dependence.
关于氟马西尼(Ro15 - 1788)是否能拮抗乙醇的中枢作用及乙醇戒断反应,存在相互矛盾的报道。用乙醇液体饲料长期喂养C57BL / 6J小鼠。对照小鼠以配对方式给予不含乙醇的等热量饲料。在乙醇戒断前即刻、戒断前14小时或24小时,给这些小鼠注射Ro15 - 1788(25毫克/千克)或赋形剂。在这些条件下,注射Ro15 - 1788的乙醇依赖小鼠中,未观察到处理诱导的戒断性癫痫发作严重程度或戒断性体温过低有所减轻。同样,在乙醇戒断第3天对小鼠进行测试时,Ro15 - 1788对乙醇的共济失调作用(睡眠时间和水平棒试验)及体温过低作用的耐受性也没有消除或减弱。结论是,Ro15 - 1788(25毫克/千克)对乙醇耐受性和依赖性没有影响。