[Effect of several antiasthmatic prophylactic drugs on bronchoconstriction induced by kerosene in rabbits]

Various authors have reported the protective effect of disodium cromoglycate (DSCG) against bronchoconstriction induced by cold air, exercise, sulfurdioxide and other agents. We also found in our experimental work the protective effect of DSCG, ketotifen and oxatomide against the contractile effect of various agonists such as histamine prostaglandin F2, acetylcholine and barium chloride on isolated guinea pig intestine and trachea. This suggests an additional effect of these drugs on cholinergic endings and/or directly on smooth muscle fibers in addition to their membrane stabilizing effects on mast cells as it has been suggested by other authors previously. To offer insight into these mechanisms we decided to evaluate the action of ketotifen, oxatomide, ICI 74917 and BRL 10833 using the model of kerosene-induced bronchoconstriction in rabbits. Here the parasympathetic pathways play an important role as it has been demonstrated by us using atropine or vagal section. Ketotifen (5 mg/kg i.v.) and oxatomide (5 mg/kg i.v.) were administered before kerosene aerosol exposure these significantly inhibited kerosene-induced bronchoconstriction, whereas ICI 74917 (10 mg/kg i.v.) and BRL 10833 (10 mg/kg i.v.) lacked this protective effect. These results support our hypothesis that an additional protective effect on smooth muscle and its innervation is involved in the mode of action of the prophylactic antiasthmatic drugs which have been clinically successful.