METABOLISM OF MECLIZINE IN THE RAT

¹ National Institute of Dental Research, National Institutes of Health, Public Health Service, Department of Health, Education and Welfare, Bethesda, Maryland

Meclizine hydrochloride was found to be metabolized by the rat. Norchlorcyclizine has been identified as one of the metabolites on the basis of chemical reactivity, ultraviolet spectrum, and paper chromatography. Once formed, norchlorcyclizine appears to circulate throughout the body of the rat as it was found in a large variety of tissues. It can also penetrate the placental barrier and was the only tertiary amine found in the fetuses of meclizine treated animals. It is suggested from this finding that this metabolite, or in turn a metabolite of it, is responsible for the congenital malformations observed in meclizine hydrochloride treatment of rats.