Duration of action and effect on baroreflex function of the anti-arrhythmic α1 antagonist UK-52,046

Author:

Spiers James P1,Harron Dean W G1,Wilson Richard1

Affiliation:

1. Department of Therapeutics and Pharmacology, Whitla Medical Building, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland

Abstract

Abstract The effects of acute and chronic oral administration of UK-52,046 (25 μg kg−1) on baroreflex function and its duration of action, were studied in conscious dogs. It was found that UK-52,046 had no effect on blood pressure and heart rate following acute and chronic administration. UK-52,046 shifted the phenylephrine dose response curve to the right, and the PE50 (measure of α1-adrenoceptor antagonism) was increased (P < 0.05) compared to placebo on day 1 (2, 4, 8 and 24 h) and day 8 (2, 4, 8 and 12 h). The antagonism was increased (P < 0.05) on day 8 (0,8 and 12 h) compared with day 1. Evaluation of the effects of UK-52,046 on baroreflex function using phenylephrine to increase blood pressure indicated no significant difference from placebo. It was concluded that at an antiarrhythmic dose, UK-52,046 has no effect on blood pressure, heart rate or baroreflex function. The pressor response curve was shifted to the right indicating a duration of action of at least 12 h on chronic oral administration.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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