Antihypertensive and cardiovascular effects of the new dihydropyridine derivative methyl (E)-3-phenyl-2-propen-1-yl-1,4-dihydro-2,6-dimethyl- 4-(3-nitrophenyl)pyridine-3,5-dicarboxylate.
The hypotensive and cardiovascular effects of a newly synthetized dihydropyridine derivative, methyl (E)-3-phenyl-2-propen-1-yl-1,4-dihydro-2,6-dimethyl-4-(3- nitrophenyl)pyridine-3,5-dicarboxylate (FRC-8411) were investigated in rats, guinea pigs, and rabbits, in comparison with nifedipine, nicardipine, and diltiazem. In conscious hypertensive rats, FRC-8411 (0.3-3 mg/kg p.o.) was found to be an orally effective antihypertensive agent and its effect lasted for more than 7 h. This effect was gradual and yet much more potent and longer than those of other reference drugs. An accompanied tachycardia was observed after oral administration of FRC-8411 and other dihydropyridine derivatives. In anesthetized rats, FRC-8411 (3-30 micrograms/kg i.v.) also showed a gradual, potent and long-lasting hypotension with a tachycardia. FRC-8411 (up to 3 mg/kg i.v.) had no effect on the PQ interval of the ECG in anesthetized rats. In isolated guinea pig atria, FRC-8411 (10(-9) - 3 X 10(-8) mol/l) showed a negative chronotropic effect, but a higher dose of the drug was needed for induction of the negative inotropic effect. In K+-depolarized rabbit aorta and guinea pig taenia coli, FRC-8411 (3 X 10(-9) - 3 X 10(-7) and 10(-7) - 3 X 10(-7) mol/l) showed a dose-dependent inhibition of the calcium-induced contraction, and its pA2 value was 8.4 and 7.1, respectively. FRC-8411 had a much higher sensitivity to the aorta than the taenia coli, though it was less potent than nifedipine and nicardipine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
D000768:Anesthesia, General; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006977:Hypertension, Renal / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C048161:pranidipine; D009543:Nifedipine