Antiasthmatic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidaz ole difumarate (KB-2413), a new antiallergic.

Effects of KB-2413 on experimental asthma and respiration were examined in comparison with ketotifen and chlorpheniramine in guinea pigs. Anaphylactic bronchoconstriction in guinea pigs were measured by two methods. One is the method measuring increase of airway resistance and the other is the method measuring change of volume and rate of respiration. KB-2413 (0.003-0.1 mg/kg p.o.) showed a dose-dependent inhibition on antigen-induced increase in airway resistance in passively sensitized guinea pigs. The ED50 value of KB-2413 was 0.012 mg/kg p.o. and the inhibitory effect of KB-2413 was 24.9 and 3.3 times more potent than those of chlorpheniramine and ketotifen, respectively. On the other hand, disodium cromoglycate did not show any inhibitory effect on this reaction at a dose of 30 mg/kg i.v. KB-2413 (0.003-0.03 mg/kg p.o.) also showed a dose-dependent inhibition on antigen-induced disorder of the respiration in passively sensitized guinea pigs. KB-2413 itself did not induce respiratory disorder at doses of 1 and 3 mg/kg i.v. and 30 mg/kg i.d. On the other hand, ketotifen and diphenhydramine induced respiratory disorder distinctly at a dose of 1 mg/kg i.v. Thus, KB-2413, by oral administration, has a very strong inhibitory effect on anaphylactic bronchoconstriction, and does not induce respiratory disorder even at about 2500 times the dose as that which showed a 50% inhibitory effect on anaphylactic bronchoconstriction.