The mechanism of action of chlorpromazine. 2. Reduced diphosphopyridine nucleotide–cytochrome <i>c</i> reductase and coupled phosphorylation

Abstract

In the previous paper (Dawkins, Judah & Rees, 1959) it was shown that 10-(3-dimethylaminopropyl)-2-chlorophenothiazine (chlorpromazine) was an inhibitor of cytochrome oxidase and also ex- hibited some action against oxidative phosphorylation. During the course of this investigation, it became apparent that chlorpromazine also had a second point of action in the respiratory chain. This paper describes experiments which indicate the site of action of chlorpromazine. Also included are some observations on the barbiturate 5-ethyl-5-isoamylbarbituric acid (Amytal), which has a very similar action (Ernster, 1956). A preliminary communication of these results has been published (Dawkins, Judah & Rees, 1958).