Cardiovascular effects of the new dihydropyridine derivative elgodipine.
The cardiovascular effects of elgodipine (IQB-875, CAS 119413-55-7), a new phenyldihydropyridine derivative, were studied and compared with those of other dihydropyridines. In isolated guinea-pig atria elgodipine, nifedipine and oxodipine decreased atrial rate and contractile force and in atrial and ventricular muscle fibres shortened the action potential duration (APD) at both 50% and 90% levels of repolarization, but had no effect on amplitude and Vmax of the upstroke or resting membrane potential. They also inhibited the amplitude of the slow contractions and decreased the amplitude and Vmax and shortened the APD of the slow action potentials elicited isoprenaline (isoproterenol) in K-depolarized fibres. In isolated perfused guinea-pig hearts elgodipine, oxodipine, nimodipine, nisoldipine, nitrendipine and nifedipine increased coronary flow and slowed conduction time through the A-V node, but they had no effect on intraatrial and intraventricular conduction times. In anaesthetized dogs the most marked effect of elgodipine was an arterial vasodilator action resulting in a decrease in systemic vascular resistance which explained the decrease in systemic blood pressure and improved left ventricular systolic performance (cardiac output and stroke volume) due to reduction of afterload. As a consequence elgodipine also decreased the pressure-rate product. It is concluded that elgodipine exerted cardiovascular effects qualitatively similar to those previously described with other Ca antagonists of the same class.
Tamargo
J
J
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
López-Sendón
J
J
Delpón
E
E
González-Morales
M
M
de Miguel
E
E
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C063839:elgodipine; D011188:Potassium