STUDIES WITH ABANOQUIL (UK-52,046) A NOVEL QUINOLINE ALPHA-1-ADRENOCEPTOR ANTAGONIST .1. EFFECTS ON BLOOD-PRESSURE, HEART-RATE AND PRESSOR RESPONSIVENESS IN NORMOTENSIVE SUBJECTS

1 Abanoquil (UK 52,046) is a novel, quinoline-derivative, alpha-1-adrenoceptor antagonist which, on the basis of animal studies, possesses antiarrhythmic activity at doses which have little or no effect on blood pressure. 2 In two placebo-controlled, double-blind, crossover studies the alpha-1-adrenoceptor antagonist activity (phenylephrine pressor responses) and the effects on blood pressure and heart rate (in the presence and absence of concomitant beta-adrencoeptor blockade) have been investigated in healthy, normotensive subjects following the intravenous administration (i.v.) of abanoquil. 3 In the first study, abanoquil at a dose of 0.4-mu-g kg-1 i.v.(as a bolus or by increments) produced significant alpha-1-adrenoceptor antagonism (with rightward shifts of more than two-fold in the phenylephrine pressor dose-response curves) but no significant effects on supine or erect blood pressure and heart rate. 4 In the second study, a dose of 0.5-mu-g kg-1 i.v. had no significant effect on supine or erect blood pressure but pre-treatment with atenolol promoted a small fall in erect blood pressure without causing significant orthostatic hypertension. 5 In conclusion, significant alpha-1-adrenoceptor antagonism without marked reflex tachycardia or profound postural hypotension suggest that abanoquil has a different haemodynamic profile from that of 'classical' peripheral alpha-1-adrenoceptor antagonists.