McNicholas L F, Martin W R, Sloan J W, Wala E
University of Kentucky, Department of Pharmacology, College of Medicine, Lexington.
J Pharmacol Exp Ther. 1988 Apr;245(1):221-4.
Dogs were made dependent on p.o. administered diazepam (24 or 36 mg/kg/day) or nordiazepam (18 mg/kg/day). Flumazenil (2, 6 or 18 mg/kg) administered p.o. once a week according to a Latin Square design precipitated abstinence in both groups of dogs. Abstinence was evaluated using a Nordiazepam Precipitated Abstinence Scale (NPAS) of various signs of abstinence and by counting seizure episodes. Flumazenil caused dose-related increases in the NPAS scores of both diazepam- and nordiazepam-dependent dogs; the slopes of the two dose-response lines were not different. Both groups of dogs also had both clonic and tonic-clonic seizures after flumazenil administration. CGS-8216 (2, 6 or 18 mg/kg) administered p.o. did not cause a dose-related elevation in NPAS scores for either group of dogs but clonic and tonic-clonic seizures were seen. Thus, flumazenil precipitates the benzodiazepine abstinence syndrome, as evidenced by tremors, tachypnea and other signs, including seizures, whereas CGS-8216 may have some selectivity in precipitating seizures without other signs of abstinence.
使犬依赖口服给予地西泮（24或36毫克/千克/天）或去甲地西泮（18毫克/千克/天）。根据拉丁方设计，每周口服给予氟马西尼（2、6或18毫克/千克），导致两组犬均出现戒断反应。使用包含各种戒断体征的去甲地西泮诱发戒断量表（NPAS）并通过计算癫痫发作次数来评估戒断反应。氟马西尼使地西泮依赖和去甲地西泮依赖的犬的NPAS评分呈剂量相关增加；两条剂量反应线的斜率无差异。给予氟马西尼后，两组犬均出现阵挛性和强直阵挛性癫痫发作。口服给予CGS - 8216（2、6或18毫克/千克）未使两组犬的NPAS评分出现剂量相关升高，但可见阵挛性和强直阵挛性癫痫发作。因此，氟马西尼可诱发苯二氮䓬类戒断综合征，表现为震颤、呼吸急促及其他体征，包括癫痫发作，而CGS - 8216在诱发癫痫发作方面可能具有一定选择性，且无其他戒断体征。
