THE CARDIOVASCULAR EFFECTS OF ICI 118,587: A β1‐ADRENOCEPTOR PARTIAL AGONIST

Abstract

In a preparation in which cardiovascular reflexes were prevented from occurring, ICI 118,587 (1‐(p‐hydroxyphenoxy)‐3‐β‐(morpholinocarbonamido) ethylamino‐2‐propranol fumarate) caused dose‐dependent positive chronotropic and inotropic effects upon the dog heart. The increase in heart rate brought about by ICI 118,587 was about 43% of the maximum increase produced by isoprenaline. For a given chronotropic effect produced by either ICI 118,587 or isoprenaline, each compound produced a similar inotropic effect as indicated by an increase in LV dp/dt max. In contrast to the direct stimulant action of ICI 118,587 on the heart no direct effects on vascular smooth muscle were observed. ICI 118,587 was shown to be a competitive antagonist of the chronotropic and vasodilator effects of isoprenaline on the heart and blood vessels and of the chronotropic effects of noradrenaline on the heart. It is concluded that ICI 118,587 is a selective β1‐adrenoceptor partial agonist. 1982 British Pharmacological Society