The in vivo pharmacological profile of histamine (H 1 ) antagonists in the rat

Thirteen known H 1 ‐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 H 1 ‐antagonists were: antimuscarinic (diphenhydramine, promethazine, mequitazine, azatadine, cyproheptadine, chlorphenriamine, clemastine, pyrilamine) and anti‐serotonin activity (mianserin, pizotifen, cyproheptadine, prometazine, diphenhydramine, pyrilamine). Sedative effects of H 1 ‐antagonists were not detected by the pharmacological tests used here. Astemizole, ketotifen, and terfenadine were found to be very specific H 1 ‐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.