Effects of the new dihydropyridine derivative 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester on the cardiohemodynamics and the energy metabolism of ischemic myocardium.
To characterize the effects of a new calcium antagonist of the dihydropyridine type, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic++ + acid methyl 6-(5-phenyl-3-pyrazolyloxy) hexyl ester (CV-159) on the cardiovascular system, experiments were performed in the anesthetized open-chest dogs and in the heart-lung preparation with a support dog in comparison with those of nicardipine. In the anesthetized dog CV-159 (1-30 micrograms/kg) produced a dose-related decrease in mean blood pressure with a decrease in total peripheral resistance, and an increase in coronary flow. There was a reflex increase in heart rate, aortic flow and left ventricular dP/dtmax. Nicardipine (1-30 micrograms/kg) produced qualitatively similar changes in these parameters, although the onset of action was quicker and the duration shorter. Hypotensive effects of CV-159 were approximately three times less potent than those of nicardipine. In doses above 3 micrograms CV-159 produced a long-lasting increase in coronary flow and slight negative inotropic and chronotropic effects in the heart-lung preparation. In doses above 1 microgram nicardipine produced an increase in coronary flow without producing any change in the cardiac functions. The increase in coronary flow produced by these two compounds was not associated with an increase in myocardial oxygen consumption. Studies conducted with 31P-NMR in the isolated perfused heart preparation of the rat demonstrated no improvement of the ischemic derangement of the myocardial energy metabolism with doses of CV-159 and nicardipine producing an increase in coronary flow rate, but no change in myocardial oxygen demand as assessed by heart rate X left ventricular pressure.
Imai
H
H
Department of Pharmacology, Niigata University School of Medicine, Japan.
Matsui
K
K
Ochi
S
S
Nakazawa
M
M
Nakagawa
Y
Y
Imai
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D004952:Esters; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004952:Esters; C055634:CV 159; D009529:Nicardipine