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Oral antiallergic activity in ascaris hypersensitive dogs: A study of known antihistamines and of the new compounds ramastine (R 57 959) and levocabastine (R 50 547)
Author(s) -
Awouters Frans,
Vermeire Jozef,
Smeyers Frans,
Vermote Patrick,
van Beek René,
Niemegeers Carlos J. E.
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430080112
Subject(s) - cyproheptadine , terfenadine , pharmacology , astemizole , ketotifen , histamine , ed50 , chemistry , antagonist , medicine , serotonin , asthma , receptor
Abstract 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 S 2 ‐antagonist ritanserin at 2.5 mg/kg and the selective histamine H 2 ‐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.