Comparative toxicology of temelastine: A novel H sub(1) antagonist in dog, rat, and monkey

The toxicity of temelastine 2-(4-(5-bromo-3-methylpyrid-2-yl)butylamino)-5-((6-methylpyrid-3-y l) methyl)-4-pyrimidone a potent, selective, competitive histamine H sub(1)-receptor antagonist was examined in dogs and rats. The major toxicological response seen in the dog was marked, but intermittent...

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Bibliographic Details
Published in:Fundamental and applied toxicology 1990-01, Vol.14 (1), p.71-83
Main Authors: Poole, A, Betton, G R, Salmon, G, Sutton, T, Atterwill, C K
Format: Article
Language:English
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Summary:The toxicity of temelastine 2-(4-(5-bromo-3-methylpyrid-2-yl)butylamino)-5-((6-methylpyrid-3-y l) methyl)-4-pyrimidone a potent, selective, competitive histamine H sub(1)-receptor antagonist was examined in dogs and rats. The major toxicological response seen in the dog was marked, but intermittent and reversible, increases in the plasma activity of a number of liver-associated enzymes, viz alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), and alkaline phosphatase (ALP). The results of the study showed the dog to be most sensitive to the hepatic effects of temelastine. The major toxicological effect of temelastine in the rat was a histopathological lesion of the thyroid gland characterized by agglomeration and depletion of colloid, follicular epithelial hyperthrophy and reduced follicular size. The no-effect dose for this lesion was between 10 and 33.3 mg/kg/day. These histopathological changes, characteristic of a "TSH-driven" thyroid gland, were not seen in the thyroid glands of dogs.
ISSN:0272-0590