Gupta M B, Nath C, Patnaik G K, Saxena R C
Department of Pharmacology, K.G. Medical College, Lucknow.
Indian J Med Res. 1996 Jun;103:310-4.
Effects of calcium channel blockers were investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg daily x days). Parameters such as body weight, food intake, spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock-aggression (FSA) and audiogenic seizures were observed during the period of administration of lorazepam and after its withdrawal. Calcium channel blockers viz. verapamil, nifedipine and nimodipine in different doses were administered orally twice daily in separate groups during the withdrawal period. The withdrawal signs observed in control group (without calcium channel blockers) were hyperkinesia, hyperthermia, hyper-aggression and audiogenic seizures. The administration of verapamil (5-20 mg/kg), nifedipine (1.75-7 mg/kg) and nimodipine (5-20 mg/kg) during the withdrawal period of lorazepam showed dose dependent significant blockade of all the withdrawal signs. Audiogenic seizures were completely blocked by 20 mg/kg dose of verapamil and nimodipine while nifedipine was partially effective. It may be concluded that calcium channel blockers exert protective effects on benzodiazepine withdrawal syndrome.
研究了钙通道阻滞剂对劳拉西泮依赖大鼠戒断症状的影响。通过按以下剂量方案将劳拉西泮与食物混合给药来产生身体依赖性：10×4、20×4、40×4、80×4和120×7（毫克/千克/天×天数）。在劳拉西泮给药期间及其撤药后，观察体重、食物摄入量、自发运动活动（SLA）、体温、对疼痛的反应时间、足部电击攻击（FSA）和听源性惊厥等参数。在撤药期间，不同剂量的钙通道阻滞剂维拉帕米、硝苯地平和尼莫地平分别给予不同组，每天口服两次。在对照组（未使用钙通道阻滞剂）中观察到的戒断症状有运动亢进、体温过高、攻击性增强和听源性惊厥。在劳拉西泮撤药期间给予维拉帕米（5 - 20毫克/千克）、硝苯地平（1.75 - 7毫克/千克）和尼莫地平（5 - 20毫克/千克）显示出对所有戒断症状的剂量依赖性显著阻断作用。20毫克/千克剂量的维拉帕米和尼莫地平完全阻断了听源性惊厥，而硝苯地平部分有效。可以得出结论，钙通道阻滞剂对苯二氮䓬类药物戒断综合征具有保护作用。
