PT - JOURNAL ARTICLE AU - HANS JÖRG GAERTNER AU - URSULA BREYER AU - GERHILD LIOMIN TI - CHRONIC ADMINISTRATION OF CHLORCYCLIZINE AND MECLIZINE TO RATS: ACCUMULATION OF A METABOLITE FORMED BY PIPERAZINE RING CLEAVAGE DP - 1973 May 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 195--201 VI - 185 IP - 2 4099 - http://jpet.aspetjournals.org/content/185/2/195.short 4100 - http://jpet.aspetjournals.org/content/185/2/195.full SO - J Pharmacol Exp Ther1973 May 01; 185 AB - Female rats were given 50 mg of chlorcyclizine per kg p.o. for 3, 7 or 14 days and sacrificed 24 hours after the last drug dose. Analysis of extracts from liver, kidney, lung, spleen and brain by thin-layer chromatography showed a continuous increase in the concentrations of chlorcyclizine, N-(p-chlorobenzhydryl)-piperazine (CBP, norchlorcyclizine) and of a novel metabolite, N-(p-chlorobenzhydryl)-ethylenediamine (CBED). Studies after longer intervals following a 14-day treatment revealed a rapid decline of chlorcyclizine, a slower decline of CBP and a distinctly retarded elimination of CBED. This metabolite (CBED) was also detected, besides CBP, in organs of rats given three 100 mg/kg doses of meclizine for six days. The identification of CBED was achieved by comparison with the synthetic compound. © 1973 by The Williams & Wilkins Co.