In vivo pharmacology of astemizole, a new type of H1-antihistaminic compound.

Astemizole (R 43 512), a chemically novel compound, has been studied for its in vivo histamine H1-antagonizing properties in laboratory animals. The test models used were: in rats, protection from compound 48/80-induced lethality and inhibition of histamine-induced skin reactions; in guinea-pigs, protection from histamine-induced fatality and bronchoconstriction and in dogs, inhibition of histamine-and Ascaris allergen-provoked skin oedema formation. When compared to standard antihistamines, astemizole showed a higher oral potency and a longer duration of action in all animal models studied. Astemizole's activity was highly specific: it exerted only weak antiserotonin and no anticholinergic actions. Behavioral and drug interaction studies showed that it was devoid of depressant or stimulatory effects on the central nervous system (CNS). Astemizole was very atoxic: safety margins were greater than 25,000 in rats and mice, 30,800 in guinea-pigs and greater than 2000 in dogs. The data of this study indicate that astemizole can be described as a potent, exceptionally long-acting and selective histamine H1-antagonist, free of central and toxic effects.