Anti-allergic properties of a new histamine antagonist, 4-(p-chlorobenzyl)-2- [N-methyl-perhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride (azelastine).

Anti-allergic properties of 4-(p-chlorobenzyl)-2 [N-methyl-perhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride (azelastine, A-5610) were investigated focusing the most attention on its decongestive effect. Intravenous injection of azelastine into anesthetized dogs with doses more than 0.1 mg/kg prevented the changes in nasal impedance provoked by histamine sprayed into the nasal cavity. When azelastine was given orally, the minimum effective dose to abolish the impedance reduction due to histamine was 2 mg/kg, in the case of cleamastine the same dose was required. Histamine release from the rat mesentery pieces by the condensation product of N-methyl-homoanisylamine formaldehyde (compound 48/80) (0.005%) was inhibited almost completely by pretreatment with azelastine at the concentrations of 10(-4) to 10(-3) g/ml, and in those concentrations azelastine alone released histamine scarcely. When 5 mg/kg of azelastine was given i.v. to rabbits, the characteristic changes in EEG -- a high-voltage low-frequency pattern -- persisted more than 1 h, but not the least inhibition in arousal response was noted. With the dose of 0.5 mg/kg, diphenhydramine impaired arousal response and slow waves with high amplitude dominantly appeared in EEG.