The effect of DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine) on monoamine oxidase activities in tissues of the rat

Abstract

The in vitro inhibition of monoamine oxidase (MAO) in rat liver, and of the clorgyline-resistant amine oxidase (CRAO) in rat heart and aorta, by DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine) has been studied. Inhibition of each enzyme activity was independent of prolonged preincubation, was reversed by dialysis, and also Ackermann-Potter plots were consistent with reversible inhibition. Simple linear competitive inhibition of MAO-A and MAO-B was observed, with Ki values of 6 × 10−6 and 8 × 10−5 m, respectively. CRAO was inhibited in a mixed, non-competitive manner (Ki of 3·2 × 10−5 and 7·8 × 10−6 m in heart and aorta, respectively) which conformed to a kinetic model in which the binding of DSP-4 to CRAO increased the affinity of substrate binding, but prevented product formation. The possible significance of these results for the in vivo actions of the drug is discussed.