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 Ki values of 6 x 10(-6) and 8 x 10(-5) M, respectively. CRAO was inhibited in a mixed, non-competitive manner (Ki of 3.2 x 10(-5) and 7.8 x 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.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D003010:Clorgyline / Q000494:pharmacology; D004351:Drug Resistance; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D001596:Benzylamines; D008995:Monoamine Oxidase; D003010:Clorgyline; C012102:DSP 4