Interaction studies in mice of SCH 29851, a potential non-sedating antihistamine, with commonly used therapeutic agents.
SCH 29851 was studied for its ability to interact with selected drugs used in man. The non-sedating antihistamine terfenadine and the sedating antihistamine diphenhydramine were also studied for comparison. SCH 29851 at 80 mg/kg po in mice, a dose about 50 times its ED50 for blocking histamine-induced paw edema in the same species, potentiated the anticonvulsant effects of diazepam. At the high dose of 320 mg/kg po, about 80 times its ED50 for antihistamine effects, SCH 29851 potentiated the ability of high doses of ethanol and hexobarbital to induce loss of righting reflexes (LRR). However, no potentiation was seen when SCH 29851 was studied with lower doses of ethanol or phenobarbital that had anticonvulsant effects but did not cause LRR. At this high dose of 320 mg/kg po, SCH 29851 also did not interact with the antihypertensive drugs propranolol and alpha-methyldopa, the anti-ulcer drug cimetidine, the nasal decongestant pseudoephedrine, or the CNS stimulant d-amphetamine. A nearly identical profile of interactions was seen with terfenadine, including potentiation of diazepam at 50 times its antihistamine ED50, potentiation of ethanol- and barbiturate-induced LRR at 80 times its antihistamine ED50, and lack of interaction effects at 320 mg/kg po with each of the other tested drugs. The demonstration in this study of the significant interactions between diphenhydramine and many of the tested drugs is consistent with the clinical experience in man that this drug does have sedating properties and significant interactions with drugs like ethanol and diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006591:Hexobarbital / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D017336:Loratadine; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects; D016593:Terfenadine; D014828:Vocalization, Animal
D001559:Benzhydryl Compounds; D006633:Histamine Antagonists; D010880:Piperidines; D017336:Loratadine; D016593:Terfenadine; D004155:Diphenhydramine; D006591:Hexobarbital