Antiallergic profile of the novel H1-antihistaminic compound levocabastine.

Levocabastine hydrochloride (R50 547, CAS79516-68-0) caused no inhibitory effect on the histamine release from rat peritoneal mast cells induced by compound 48/80, A23187 and concanavalin A. However, the drug inhibited histamine release from passively sensitized mast cells and passive peritoneal anaphylaxis in rats, though higher concentrations or doses were required. Moreover, levocabastine provided a relatively potent inhibitory effect on histamine release from lung pieces of actively sensitized guinea pigs exposed to antigen, and simultaneously the drug prevented a decrease in the cyclic AMP (cAMP) content. Levocabastine potently inhibited histamine-induced cutaneous reactions in rats and the drug also prevented histamine-induced contraction of isolated guinea pig ileum. Levocabastine did not induce any significant changes in platelet aggregation or in the contraction of guinea pig ileum induced by platelet activating factor (PAF). However, the drug inhibited eosinophil migration induced by PAF. The chemotaxis of neutrophils induced by N-formyl-methionyl-leucylphenylalanine (fMLP) was also inhibited by levocabastine in a dose-dependent fashion. Levocabastine has no influence on the order parameter tested with liposomes, suggesting that the drug provides no significant effect on the membrane fluidity of lipid bilayer. These results seem to indicate that the antiallergic effect of levocabastine is mainly dependent on its potent antihistaminic activity.