Studies with abanoquil (UK‐52,046) a novel quinoline alpha 1‐ adrenoceptor antagonist: I. 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‐ adrenoceptor 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 micrograms 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 micrograms 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 hypotension. 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.