Effects of 4-(2-Alkylthio-1-benzyl-5-imidazolyl)-Dihydropyridines on the Isolated Rat Colon and Right Atrium Contractility

In order to provide a pharmacological profile for some newly synthesized dihydropyridines, we investigated their effects on the isolated rat colon segments and the isolated rat atrium contractility. The tested compounds include alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by 2-alkylthio-1-benzyl-5-imidazolyl substituent, and nifedipine as a positive control substance. Isolated rat colon and atrial tissues were prepared. Rat colon was contracted with 80 mM KCl, and maximum response was recorded (100%). After washing tissue with Krebs solution it was preincubated with different concentrations of test compounds and again KCl was added and percent change in contraction was calculated. Spontaneous contractions and its frequency for colon and atrium before and after addition of test compounds were also recorded and percent change was calculated. Nifedipine (10-8 -10-5 M) was used as positive control at all experiments.The compounds showed similar effects to that of nifedipine on the isolated rat colon. The potency of these analogues with concentration range 10-5 to 10-4 M was compared to potency of nifedipine which was effective at 10-8 to 10-5 M (P<0.01). However, unlike nifedipine, the test compounds exerted significant positive inotropic effect on the isolated rat atrium (P < 0.01). Our observations suggest that these analogues of nifedipine selectively enhance contractility of heart muscle while causing relaxation of intestinal smooth muscle. These compounds may serve as valuable probes to develop novel dihydropyridines with dual smooth muscle relaxant effect and positive inotropic action.