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)

Autor: Carlos J. E. Niemegeers, Frans Awouters, Jozef Vermeire, Frans Smeyers, Patrick C. M. Vermote, René van Beek
Rok vydání: 1986
Předmět:
Zdroj: Drug Development Research. 8:95-102
ISSN: 1098-2299
0272-4391
DOI: 10.1002/ddr.430080112
Popis: 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.
Databáze: OpenAIRE
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