The present study was aimed to develop an in-vitro model for estimating the potency of three H1-antagonists (chlorpheniramine maleate, promethazine theoclate and dimenhydrinate). We have evaluated histamine-induced contractions in various tissues such as guinea-pig ileum, rat ileum, goat ileum and goat tracheal smooth muscle in absence and presence of various concentrations of antihistamines. Histamine-induced contractions were H1-receptor-mediated effect, which were competitively inhibited by the antihistamines. The pD2 values of chlorpheniramine maleate, promethazine theoclate and dimenhydrinate were found to be 8.67±0.00, 7.78±0.00 and 6.35±0.00 in g.pig ileum, 6.67±0.00, 5.78±0.00 and 4.61±0.00 in rat ileum, 6.37±0.00, 5.48±0.00 and 4.37±0.00 in goat ileum, and 6.29±0.00, 5.36±0.00 and 4.27±0.00 in goat trachea respectively. There appeared to be a marked difference in sensitivity to histamine in the tissue preparations used. The pA2 values of chlorpheniramine maleate, promethazine theoclate and dimenhydrinate were found to be 7.98±0.02, 6.93±0.03 and 5.47±0.02 in g.pig ileum, 5.69±0.03, 4.79±0.02 and 3.75±0.01 in rat ileum, 5.38±0.02, 4.45±0.01 and 3.37±0.02 in goat ileum and 5.25±0.01, 4.33±0.02 and 3.27±0.03 in goat trachea respectively by Schild plot method. The contractions were concentration-dependent and surmountable and slope was not significantly different from unity, which indicates that nature of antagonism of antihistamines were reversible and competitive type. The results indicated, the increasing order of potency of antihistamines as dimenhydrinate < promethazine theoclate < chlorpheniramine maleate.
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