Pharmacology of BMY 20064, a potent Ca2+ entry blocker and selective alpha 1-adrenoceptor antagonist.

BMY 20064 is a dihydropyridine Ca2+ entry blocker with potent and selective alpha 1-adrenoceptor antagonist properties. The drug was equal in potency to nifedipine as a Ca2+ entry blocker in depolarized smooth muscle preparations. It was less active than nifedipine in antagonizing Ca2+-induced contractions of isolated guinea pig papillary muscles paced at 0.2, 1.0, or 2 Hz. BMY 20064 was a potent (0.1-0.2 X prazosin) and selective alpha 1-adrenoceptor antagonist in radioligand binding assays and in ganglion-blocked anesthetized rats challenged with phenylephrine. BMY 20064 blocked both the K+ and alpha 1-adrenergic agonist-induced increases in 45Ca uptake into rabbit aortic rings. The drug was more effective than nifedipine, prazosin, or combinations of the drugs in preventing ATP depletion of the rat heart during global ischemia. BMY 20064 was a potent antihypertensive agent in normotensive rats and in SHR. BMY 20064 administered intraarterially (i.a.) dilated both femoral and coronary arterial beds of the dog. Hemodynamic changes elicited by BMY 20064 in anesthetized dogs were similar to those induced by nifedipine. BMY 20064 appears to be a more effective myocardial antiischemic agent than nifedipine, prazosin, or combinations of nifedipine and prazosin. A drug of this type may be more efficacious than dihydropyridines in the management of ischemic episodes.