Barmastine

The antiallergic effectiveness of twelve compounds was studied in ascaris hypersensitive dogs by measuring allergen‐induced skin reactions before and 1, 4, 20, and 72 hr after oral treatment. The specific serotonin S2‐antagonist ritanserin at 2.5 mg/kg and the selective histamine H2‐antagonist cimetidine at 10 mg/kg did not reduce the allergic wheals. Chlorpheniramine and clemastine were inactive at 2.5 mg/kg. The remaining eight compounds studied over a wide dose range produced peak activity at markedly different doses and time intervals (hr). The lowest oral ED50‐values in mg/kg were: levocabastine: 0.0035 (4); R 57 959: 0.048 (20); astemizole: 0.13 (20); ketotifen: 0.20 (4); cyproheptadine: 0.21 (4); azatadine: 0.32 (4); oxatomide: 1.26 (20); terfenadine: 1.26 (1). The lowest oral ED50‐values in dogs and in rats (compound 48/80 lethality test) were similar, the largest difference being a fourfold potency gain of oxatomide in dogs. The short‐acting compounds in rats (azatadine, cyproheptadine, ketotifen, and terfenadine) had also a duration of action of less than 12 hr in dogs. Levocabastine, R 57 959, astemizole, and oxatomide acted more than 16 hr. Maximal inhibition of the allergic wheal volumes was highest with levocabastine (90%); it reached 80% with R 57 959 and ranged from 67 to 78% with the remaining compounds. On the basis of their activity characteristics in dogs, levocabastine and R 57 959 are potentially very effective antiallergic drugs.