Journal of Kerman University of Medical Sciences (Dec 2003)
Effect of New Derivatives of Dihydropyridine on Rat Ileal Smooth Muscle in Vitro
Abstract
In this research we evaluated the calcium channel antagonist activity of various diester analohues of nifedipine on rat ileal smooth muscle.in these analogues,the orthophenyl group at position 4 was replaced by 1 methyl 2-meythylsulfonyl or methylthio 5-imidazolyl.wistar rats(180-250g) were killed by a blow to the head.the intestine was removed above the ileucecal junction and longitudinal smooth muscle segments of 2 cm length were maintained at 37c in a 10 ml jacket organ bath containing oxygenated intestinal krebs soluion.the contractions was recorded with a force displacement transducer connected to a physiograp.the contraction was elisited with 80 mmol KCL.test compounds were cumulatively added to produse 50% relaxation of contracted ileal smooth muscle (IC50) THAT WAS DETERMINED FROM THE CINCENTRATION response trace recorded by physiograph.the IC50 of nifedipine was (1.26+-0.37)*10 and of compounds 1,2,3,4,5 and 6 was(2.57+_0.28)*10,(1.03+_0.12)*10,(2.55+_0.50)*10,(1.32+_0.18)*10,(3.16+_0.89)*10, and (1.04+_0.29)*10 mole respectively.the results indicate that replacement of 2_ nitrophenyl at C4 position of nifedipine with methyltion or methyl solfunyl imidazolyl reduces the activity.the comparison of the activites of symetrical esters(compounds No 3&6) indicated that increasing the length of methylen chain in C3 and C5 esters substituend decreases the avtivity.Comparison of the activities of asymetrical esters(compounds No4&5) indicates that,when at C3 there is a small substituent,increasing the length of methylen chain increases activity.comparison of the activites of symetrical esters(compounds 2 and 3) with asymetrical esters(compounds 1,4.5 and 6) indicates that asymetrical esters are not always more potent than symmetrical esters.compound 4 was the most potent new compound in this study.finally we can conclude that nifedipine was significantely more potent than all of these compounds.
