Reconsideration of vascular selectivity of dihydropyridine calcium antagonists: comparison of cardiovascular profile of mepirodipine, a novel dihydropyridine consisting of a single stereoisomer with (+)-(S)-(S) conformation, with those of nifedipine and nicardipine.
The coronary vasodilator effect and negative chronotropic, inotropic and dromotropic effects of mepirodipine, the single stereoisomer of a novel dihydropyridine Ca antagonist, were compared with those of nifedipine and nicardipine using canine isolated, blood-perfused heart preparations. Drugs were injected into each nutrient artery. In the sinoatrial node preparation, the dose producing a 15% decrease in sinoatrial rate was 1.3, 6.5 and 2.5 micrograms for mepirodipine, nifedipine and nicardipine, respectively. In the papillary muscle preparation, the dose causing a 50% decrease in developed tension was 44, 6.5 and 54 micrograms for mepirodipine, nifedipine and nicardipine, respectively. The dose causing a 50% increase in blood flow through the anterior septal artery was 0.26, 0.18 and 2.0 micrograms for mepirodipine, nifedipine and nicardipine, respectively, while the time required for return to half maximum at the above dose was 13.1, 1.8 and 4.1 min, respectively. In the atrioventricular node preparation, the dose producing a 50% increase in AH interval was 1.6, 2.4 and 3.7 micrograms for mepirodipine, nifedipine and nicardipine, respectively. These results indicate that mepirodipine is a potent and long-lasting dihydropyridine Ca antagonist, whose vascular selectivity is highest against cardiac contractility, but less selective against sinoatrial node automaticity and atrioventricular nodal conduction, compared with nifedipine.
Motomura
S
S
Department of Pharmacology, Yamanashi Medical College, Japan.
Hashimoto
K
K
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; C050699:mepirodipine; D009529:Nicardipine; D009543:Nifedipine