Cromakalim, a potassium channel activator: a comparison of its cardiovascular haemodynamic profile and tissue specificity with those of pinacidil and nicorandil.
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 nicorandil was 10 times less potent than pinacidil. Cromakalim and pinacidil had a similar duration of action while nicorandil 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 nicorandil were highly specific as inhibitors of tension in vascular (rabbit portal vein) (IC50 = 2.1 x 10(-8), 4.6 x 10(-8), and 1.3 x 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.
Longman
S D
SD
Beecham Pharmaceuticals Research Division, Harlow Essey, England.
Clapham
J C
JC
Wilson
C
C
Hamilton
T C
TC
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D019806:Cromakalim; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D009928:Organ Specificity; D010210:Papillary Muscles / Q000187:drug effects; D020110:Pinacidil; D011169:Portal Vein / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D000959:Antihypertensive Agents; D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil