The influence of 3-ester side chain variation on the cardiovascular profile of nitrendipine in porcine isolated trabeculae and coronary arteries.
It has been reported that the lipophilicity of dihydropyridine-type calcium entry blockers may influence both their negative inotropic and their vasodilator activities. The action of nitrendipine and six related 3-ester side-chain derivatives with increasing alkyl and aryl substituents have been investigated in isolated porcine trabecular muscles and coronary artery rings. The lipophilicity of the drugs was determined by high-pressure liquid chromatography. In addition, some sterical parameters of the ester derivatives were considered. For the drugs tested, an increase in 3-ester side chain volume correlated well with increasing lipophilicity. Compared to nitrendipine, vascular selectivity of the ester side-chain derivatives, as expressed by the ratio of their negative inotropic and vasodilator activities, was much reduced. Neither vasodilator nor negative inotropic activity was directly related to the corresponding lipophilicity. Based on these results, earlier suggestions about the influence of the ester side-chain in dihydropyridines on their cardiovascular profile are extended.
Kojda
G
G
Institut für Pharmakologie, Universität zu Köln, Federal Republic of Germany.
Klaus
W
W
Werner
G
G
Fricke
U
U
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003331:Coronary Vessels / Q000187:drug effects*; D003864:Depression, Chemical; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry; D009200:Myocardial Contraction / Q000187:drug effects; D009568:Nitrendipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
D008055:Lipids; D014665:Vasodilator Agents; D011189:Potassium Chloride; D009568:Nitrendipine