title: Antiallergic effects of major metabolites of astemizole in rats and guinea pigs.
abstract: Antiallergic effects of astemizole (CAS 68844-77-9) and its metabolites were studied using rats and guinea pigs. All the metabolites of astemizole tested i.e., desmethylastemizole, 6-hydroxydesmethylastemizole and norastemizole, were more active than astemizole in inhibiting the contraction of the ileum as well as the bronchoconstriction induced by histamine in guinea pigs. Desmethylastemizole was about the same as the parent compound in inhibiting the 3H-mepyramine binding in guinea pig cerebellum. In heterologous passive cutaneous anaphylaxis (PCA) and homologous PCA, the metabolites caused almost equipotent inhibition to that seen in astemizole. On the other hand, in the studies of histamine release from rat peritoneal mast cells induced by compound 48/80 or from lung fragments in actively sensitized guinea pigs, desmethylastemizole, 6-hydroxydesmethylastemizole and norastemizole were much less potent than was astemizole. No H2-antagonistic activity was observed with either astemizole or desmethylastemizole.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kamei
authors.forename: M
authors.initials: M
authors.lastname: Mio
authors.forename: K
authors.initials: K
authors.lastname: Izushi
authors.forename: K
authors.initials: K
authors.lastname: Kitazumi
authors.forename: S
authors.initials: S
authors.lastname: Tsujimoto
authors.forename: K
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: K
authors.initials: K
authors.lastname: Tasaka
mesh_terms: D000818:Animals; D016589:Astemizole / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D006635:Histamine H2 Antagonists; D003189:p-Methoxy-N-methylphenethylamine; D016589:Astemizole; D011738:Pyrilamine