Effects of azelastine hydrochloride, a novel anti-allergic drug, on the central nervous system.
The effects of 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinone hydrochloride (azelastine hydrochloride), a new anti-allergic drug, on the central nervous system were studied in mice, rats and rabbits in comparison to clemastine, chlorpheniramine and diphenhydramine. In mice, azelastine showed a definite central action with the same dose range (10--40 mg/kg p.o.) as the reference drugs. However, the central action profile of azelastine was considerably different from those of the reference antihistaminics. Clemastine and diphenhydramine produced potent anti-tremorine and anti-pilocarpine activities, while azelastine was less active than the two drugs. Chlorpheniramine and diphenhydramine produced a marked anti-reserpine activity and a marked potentiation of the caffeine-induced hypermotility, while clemastine had little effect in this animal model; on the contrary, 40 mg/kg of azelastine suppressed the caffeine-induced hypermotility. In rats, a high dose of 100 mg/kg azelastine produced a slight suppression of the paradoxical sleep. But the drug affected neither the rectal temperature nor the conditioned avoidance response at oral doses up to 100 mg/kg. In unanesthetized and restrained rabbits, azelastine in a dose of 0.5 to 8 mg/kg i.v. showed no significant change in the spontaneous EEG activity and in the susceptibility of the ascending reticular activating system, whereas an i.v. dose of 2 mg/kg clemastine produced a marked high voltage and slow wave pattern in EEG activity and suppressed the reticular activating system.
D000374:Aggression / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants; D001362:Avoidance Learning / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D004347:Drug Interactions; D004569:Electroencephalography; D006120:Grooming / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D010862:Pilocarpine / Q000037:antagonists & inhibitors; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012890:Sleep / Q000187:drug effects
D000927:Anticonvulsants; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011724:Pyridazines; D010862:Pilocarpine; C020976:azelastine