Cardiovascular effects of a new inotropic agent, U. K. 14275, in patients with coronary heart disease.

Abstract

1 The chronotropic and inotropic properties of U.K. 14275, a phosphodiesterase inhibitor were assessed in patients with coronary heart disease. 2 Left ventricular function was assessed in eight patients with acute myocardial infarction using the non‐invasive measurement of systolic time intervals. 3 Twelve patients with angina pectoris were studied during diagnostic coronary arteriography. Left ventricular function was assessed using a high fidelity catheter tipped transducer in the left ventricle. 4 In both groups of patients U.K. 14275 infused intravenously in doses of 32, 64, 128 and 256 microgram kg‐1 bodyweight min‐1 enhanced the contractile state of the left ventricle without altering the heart rate.

Haemodynamic effects of BM 10.188, a new orally active inotropic agent, in healthy volunteers.

“…Shortening of the LVET and PEP has been demon-strated following administration of the ,3-adrenoceptor agonist isoprenaline (Harris et al, 1966;Lewis et al, 1972) and similar changes have been shown with the 8/ I-adrenoceptor agonist prenalterol (Hutton et al, 1980). Other compounds with inotropic activity but with different modes of action, for example the phosophodiesterase inhibitors, also exhibit changes in LVET and PEP (Hutton et al, 1977). The present study was designed to determine whether or not a new 3-sympathomimetic agent had any detectable effect on these non-invasive indices.…”

“…Other compounds with inotropic activity but with different modes of action, for example the phosophodiesterase inhibitors, also exhibit changes in LVET and PEP (Hutton et al, 1977). The present study was designed to determine whether or not a new 3-sympathomimetic agent had any detectable effect on these non-invasive indices.…”

Electrophysiological and haemodynamic effects of a new inotropic agent (UK 14275) in the dog

“…A recently developed inotropic compound UKI 4275, 1 -butyl-3( 1 (6,7dimethoxyquinazolin-4.~1) piperidin4-yl urea), chemically unrelated to currently available inotropic agents, and thought to act by inhibition of myocardial phosphodiesterase thereby increasing tissue concentrations of adenosine 3',5'cyclic monophosphate (CAMP), has been shown to exert a powerful inotropic effect with minimal effect on heart rate in dogs (Follath et al, 1976) and humans (Hutton et al, 1977). Such properties could be advantageous in the management of cardiac failure over those of currently available inotropic agents.…”