MITIGATION OF CAFFEINE-INDUCED FETOPATHY IN MICE BY PRETREATMENT WITH β-ADRENERGIC BLOCKING AGENTS*

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Abstract
Fetopathic effects of caffeine were previously shown to be significantly reduced by pretreatment with propranolol at dosage levels of 2.5-10 mg/kg. The relation between time intervals of propranolol pretreatment and its effect on reducing fetopathy were investigated. The effect of timolol, another .beta.-adrenergic blocking agent, on reducing fetopathy was compared with that of propranolol. Propranolol (5 mg/kg) administered 15, 30 or 60 min before caffeine treatment significantly reduced the caffeine-induced fetopathy. The optimal effect was found when propranolol was given 30 min before caffeine. The reduction in fetopathy by timolol pretreatment was comparable to that of propranolol. The hypothesis was supported that the fetopathic effect of caffeine was linked with released catecholamines in maternal or fetal tissues of mice.