The effect of the new Dihydropyridine derivative on the ileal smooth muscle of rat in the

Structurally diverse groups of compounds are known to be effective as Calcium antagonists. The most potent class of antagonists comprises derivatives of 1, 4 Dihydropyridine of which the most widely known agent is Nifedipine. This class of compounds has been subject of many structure-activity relationship studies. In this research we evaluated the Calcium channel antagonists activity of various diester analogues of Nifedipine on rat ileal smooth muscle. In these analogues, the Orthophenyl group at position 4 is replaced by 1 Methyl-2-Meythlusulfonyl or Methylthio-5 Imidazolyl. Wistar rats (180-250 g) were killed by a blow to the head. The intestine was removed above the ileocecal junction and longitudinal smooth muscle segments of 2 cm length were maintained at 37°C in a 10 ml jacket organ bath containing oxygenated intestinal Krbps solution. The contraction were recorded with a forced displacement transducer connected to a physiograph. The contraction was elicited with 80 mmol kcl. Test compounds were cumulatively added to produce 50% relaxation of contracted ileal smooth muscle (IC50) that was determined from the concentration response trace recorded by physiograph. The comparison of activities of symmetrical esters indicates that increasing the length of methylen chain in C3 and C5 esters substituent decreased the activity and comparison of activities of a symmetrical ester, compound indicate when at C3 was a small substituent, increasing the length of methylen chain increase activity.