Cromakalim, a potassium channel activator: a comparison of its cardiovascular haemodynamic profile and tissue specificity with those of pinacidil and nicorandil
Longman, S.D.; Clapham, J.C.; Wilson, C.; Hamilton, T.C.
Journal of Cardiovascular Pharmacology 12(5): 535-542
1988
ISSN/ISBN: 0160-2446 PMID: 2468052 Document Number: 326249
Studies have been performed to compare the cardiovascular haemodynamic profiles of the potassium channel activator, cromakalim (BRL 34915), with those of pinacidil and nicorandil. In conscious renal hypertensive cats, cromakalim was 10 times more potent than pinacidil as an antihypertensive agent while nicroandil was 10 times less potent than pinacidil. Cromakalim and pinacidil had a similar duration of action while nicroandil was short acting. In anaesthetised cats, hypotension evoked by intravenous infusions of cromakalim, pinacidil, or nicorandil was associated with a decrease in mesenteric vascular resistance but only cromakalim produced a marked reduction in renal vascular resistance. Cromakalim, pinacidil, and nicrorandil were highly specific as inhibitors of tension in vascular (rabbit portal vein) (IC50 = 2.1 .times. 10-8, 4.6 .times. 10-8, and 1.3 .times. 10-6 M, respectively), rather than cardiac (rabbit papillary muscle), tissue. In view of its antihypertensive efficacy, specificity for vascular tissue, and beneficial effect upon renal haemodynamics, the potassium channel activator, cromakalim, has advantages in its profile of activity compared to pinacidil and nicorandil.