The in vivo pharmacological profile of histamine (H1) antagonists in the rat

Abstract Thirteen known H1‐antagonists were studied in a series of pharmacological in vivo tests in rats. Antihistamine activity, oral absorption, and duration of action were determined in the compound 48/80 test. The dissociation between the activity in the compound 48/80 test and in the other tests was used as a measured of antihistaminic specificity. Properties common to several H1‐antagonists were: antimuscarinic (diphenhydramine, promethazine, mequitazine, azatadine, cyproheptadine, chlorphenriamine, clemastine, pyrilamine) and anti‐serotonin activity (mianserin, pizotifen, cyproheptadine, prometazine, diphenhydramine, pyrilamine). Sedative effects of H1‐antagonists were not detected by the pharmacological tests used here. Astemizole, ketotifen, and terfenadine were found to be very specific H1‐antagonists. For ketotifen and terfenadine, oral activity (1/5 and 1/25 of astemizole, respectively) and oral absorption (1/50 and 1/7 respectively) were poor, and the duration of action (4 and 6 hr, respectively) was relatively short. Astemizole was as potent orally as it was subcutaneously (ED50 = 0.11 mg/kg) and appeared to have a duration of action as long as 24 hr.