Kulcsár-Gergely J
Department of Pharmacology, Medical University, Debrecen, Hungary.
Arzneimittelforschung. 1989 Jul;39(7):782-5.
Three nonselective beta-adrenoceptor blockers, propranolol, cloranolol and talinolol, were examined in male rats. The amount and function of polysubstrate monooxygenase, serum bilirubin and carbohydrate metabolism were investigated. Doses producing a 25% reduction in heart beat/min were given orally. The effect of a single dose was compared to that of a 12-day treatment period. Propranolol in a single dose did not influence hepatic parameters. The 12-day treatment reduced the amount of cytochrome P-450 (cP-450) and prolonged hexobarbital biotransformation time. Cloranolol decreased cP-450, prolonged hexobarbital anaesthesia and inhibited aminopyrine-N-demethylation (AND) even in a single dose. No further impairment occurred with continued treatment. A single dose of talinolol led to cP-450 loss and inhibited cP-450 dependent liver functions. This inhibition progressed with continued treatment. High bilirubin levels were measured. Both cloranolol and talinolol elicited an initial rapid hyperglycaemia with normal liver glycogen content. At the end of the treatment blood glucose and liver glycogen values were normal. The reversible hyperglycemic reaction shows the necessity of controlling glucose tolerance. When talinolol is administered liver function parameters should be checked in appropriate time intervals.
在雄性大鼠中对三种非选择性β-肾上腺素能受体阻滞剂普萘洛尔、氯萘洛尔和他林洛尔进行了研究。对多底物单加氧酶的量和功能、血清胆红素和碳水化合物代谢进行了调查。口服给予使心跳/分钟降低25%的剂量。将单次给药的效果与12天治疗期的效果进行了比较。单次给药的普萘洛尔不影响肝脏参数。12天的治疗减少了细胞色素P-450（cP-450）的量并延长了己巴比妥的生物转化时间。氯萘洛尔降低了cP-450，延长了己巴比妥麻醉时间并抑制了氨基比林-N-去甲基化（AND），即使是单次给药也是如此。持续治疗未出现进一步损害。单次给药的他林洛尔导致cP-450减少并抑制了依赖cP-450的肝功能。这种抑制随着持续治疗而进展。测得高胆红素水平。氯萘洛尔和他林洛尔均引发了初始快速高血糖症，肝脏糖原含量正常。治疗结束时血糖和肝脏糖原值正常。可逆性高血糖反应表明控制葡萄糖耐量的必要性。当给予他林洛尔时，应在适当的时间间隔检查肝功能参数。
