title: Antiallergic effects of astemizole on immediate type hypersensitivity reactions.
abstract: Astemizole (0.5-5 mg/kg, p.o.) dose-dependently inhibited heterologous and homologous PCA reactions in rats at ID50 values of 1.48 mg/kg and 2.37 mg/kg, respectively. The inhibitory effect of astemizole on heterologous PCA was most remarkable when this compound was given p.o. 2 h prior to antigen challenge. Astemizole (0.1-5 mg/kg, p.o.) dose-dependently inhibited experimentally-induced asthma in guinea pigs at an ID50 of 0.86 mg/kg. Ex vivo, astemizole (0.5-5 mg/kg, p.o.) inhibited antigen-induced histamine release from lung pieces of sensitized guinea pigs. In in vitro experiments, the drug dose-dependently inhibited antigen-induced histamine and SRS-A releases from guinea pig lung pieces at concentrations of 0.05-10 microM. Furthermore, astemizole (0.1-10 microM) inhibited the histamine release induced by compound 48/80 and antigen-antibody reaction from rat peritoneal mast cells, and at 0.1-500 nM inhibited both leukotriene C4- and platelet-activating factor (PAF)-induced contraction of isolated guinea pig trachea at submicromolar concentrations. Astemizole not only inhibited 45Ca uptake into rat mast cells but also prevented the Ca2+ release from the intracellular Ca store induced by compound 48/80, although this compound did not affect the histamine release from permeabilized mast cells induced by Ca2+. Our results suggest that one of the antiallergic mechanisms of astemizole may be an inhibition of signal transduction from the mast cell membrane to the intracellular systems.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tasaka
authors.forename: M
authors.initials: M
authors.lastname: Akagi
authors.forename: K
authors.initials: K
authors.lastname: Izushi
authors.forename: M
authors.initials: M
authors.lastname: Mio
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016589:Astemizole; D001249:Asthma / Q000188:drug therapy; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D013189:SRS-A; D016589:Astemizole; D002118:Calcium