Inhibitory Action of Chlorpromazine on the Oxidation of D-Amino-Acid in the Diencephalon Part of the Brain

Abstract

AMONG several substances examined in our laboratory for their influence on the activity of D-amino-acid oxidase, chlorpromazine (N-(3′-dimethylaminopropyl)-3-chlorophenothiazine hydrochloride) was found to be a powerful inhibitor of this enzyme. The inhibitory mechanism was investigated using a purified oxidase enzyme system and Warburg manometer, and the kinetic study carried out. D-Amino-acid oxidase protein was prepared from hog kidney by the method of Negelein and Brömel¹. Each enzyme system consisted of apo-enzyme (protein E), 1.6 × 10⁻⁷ mole of flavin adenine dinucleotide prepared by the method of Yagi et al. ², 6.25 × 10⁻² mole of D-alanine. Amounts of chlorpromazine (supplied by Rhône-Poulenc-Specia) ranging from 2 × 10⁻⁵ to 4 × 10⁻⁶ mole were added to these enzyme systems.