[Effect of 1-[3-[4-(diphenylmethyl)-1-priperazinyl]-propyl]-1,3-dihydro-2H-benzimidazol-2- one (oxatomide) on contraction of canine bronchial muscle]

Abstract

Effect of oxatomide on contraction of canine bronchial smooth muscle caused by administration of histamine and by challenge of ascaris-antigen were investigated and compared against the effects of histamine H1-receptor antagonist (CPM) and inhibitor of histamine release from mast cells (DSCG). Oxatomide in concentrations of 0.05 microgram/ml to 2.0 microgram/ml inhibited, dose-responsively, contraction of bronchial smooth muscle strip by administration of histamine (10 micrograms/ml). When this concentration was less than 0.3 microgram/ml, CPM inhibited the contraction significantly stronger than oxatomide. However, in concentration over 0.5 microgram/ml, no difference in inhibitory effect could be demonstrated. On the other hand, DSCG could not inhibit the contraction. Oxatomide in concentrations of 0.05 microgram/ml to 1.0 micrograms/ml inhibited, dose-responsively, contraction of the muscle strip sensitized spontaneously by ascaris antigen challenges. There was no difference in inhibitory effect between oxatomide and DSCG at the same level of concentration. Oxatomide (0.5 microgram/ml) and CPM (0.5 microgram/ml) both inhibited completely the constriction response of bronchus caused by histamine stimulation (10 micrograms/ml). Although constriction response by ascaris antigen challenge was inhibited completely by oxatomide (0.5 microgram/ml), it could not be inhibited completely by CPM (0.5 microgram/ml). Oxatomide inhibited even the residual constriction response which could not accomplished by CPM. These results suggest that oxatomide might have not only an effect as a histamine H1-receptor antagonist and anti-histamine releasing agent from mast cell, but also anti-SRS-A.