UNIQUE BETA ADRENERGIC STIMULATION AND BLOCKADE BY QUINTERENOL

¹ Department of Pharmacology, Medical Research Laboratories, Pfizer Inc. Groton, Connecticut

Quinterenol was evaluated for its effect on selected isolated beta adrenergic systems. In uterine, tracheal and atrial preparations quinterenol caused beta adrenergic activation, as indicated by the ability of propranolol to block its effects. In atrial preparations this effect was unique in that 1) it did not appear unless the tissues were incubated in quinterenol solution for at least six minutes and then washed, suggesting a peculiar type of autoinhibition phenomenon, 2) rate acceleration without a positive inotropic effect occurred and 3) the rate acceleration was specificaUy antagonized by chlorpromazine. In rat uterus experiments, the autoinhibition phenomenon was demonstrated occasionally at submaximal doses of quinterenol, but antagonism of quinterenol by chlorpromazine could not be shown. In contrast, autoinhibition did not occur in tracheal experiments, but chlorpromazine did block the effects of quinterenol. The specific antagonism by chlorpromazine suggests that quinterenol acts at sites different than the isoproterenol sites. In atria the quinterenol sites might be equivalent to the beta-1 rate receptor sites recently described by Farmer et al. (J. Pharm. Pharmacol. 22: 61-63, 1970). Quinterenol had approximately equally potent beto adrenergic activating effects on the beta-1 receptor systems of cardiac muscle and adipose tissue and the beta-2 receptor system of uterus but failed to activate significantly the beta-2 receptor system of gut. Thus, quinterenol did not discriminate between the two types of beta receptors.