A PHARMACOLOGICAL STUDY OF N-METHYL- N'-(4-CHLOROBENZHYDRYL) PIPERAZINE DIHTYDRO-CHLORIDE—A NEW ANTIHISTAMINIC

Pharmacological studies with N-methyl-N'-(4-chlorobenzhydryl) piperazine dihydrochloride (Compound No. 47-282), Chlorcyclizine, revealed the following: 1. Chlorcyclizine showed marked activity against the spasmogenic action of histamine on isolated tracheal and intestinal musculature. To a lesser degree, it inhibited the contractions produced by acetylcholine and barium. 2. When given orally, in relatively small doses, Chlorcyclizine prevented or reduced for over 23 hours the severity of bronchoconstriction following exposure of guinea pigs to an atmosphere of nebulized histamine. 3. The depressor effects of small doses of histamine and acetylcholine were decreased by intravenous administration of Chiorcyclizine in dogs. At the same time, the pressor effect of epinephrine was enhanced. 4. The local anesthetic action of Chiorcyclizine when injected intradermally in guinea pigs was found to be comparable to that of diphenhydramine (Benadryl). 5. Unlike Benadryl, Chlorcyclizine failed to produce mydriasis when instilled in the rabbit's eye. 6. Acute toxicity in mice and chronic toxicity in rats and dogs revealed that Chlorcyclizine is a relatively non-toxic drug, compared to doses found to be effective in humans.