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

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 K values of 6 × 10 and 8 × 10 m, respectively. CRAO was inhibited in a mixed, non‐competitive manner (K of 3·2 × 10 and 7·8 × 10 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. 1981 Royal Pharmaceutical Society of Great Britain