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.

Abstract

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.

• Authors: R F Schafers, H L Elliott, C A Howie, J L Reid
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 32 Issue 5 Pg. 599-604 (Nov 1991) ISSN: 0306-5251 [Print] England
• PMID: 1683249 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Adrenergic alpha-Antagonists
• Aminoquinolines
• Tetrahydroisoquinolines
• Phenylephrine
• Atenolol
• abanoquil

Topics

• Adrenergic alpha-Antagonists (pharmacology)
• Adult
• Aminoquinolines (administration & dosage, pharmacology)
• Atenolol (pharmacology)
• Blood Pressure (drug effects)
• Double-Blind Method
• Heart Rate (drug effects)
• Humans
• Injections, Intravenous
• Male
• Phenylephrine (antagonists & inhibitors, pharmacology)
• Tetrahydroisoquinolines