Document Type : Original Article
Authors
1 Assistant professor
2 Associate professor
3 Instructor
4 Other
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.
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