The enzyme-activated irreversible inhibition of type-B monoamine oxidase by 3-(4-[(3-chlorophenyl)methoxy]phenyl)-5-[(methylamino) methyl]-2-oxazolidinone methanesulphonate (compound MD 780236) and the enzyme-catalysed oxidation of this compound as competing reactions

Biochem J. 1983 Jan 1;209(1):235-42. doi: 10.1042/bj2090235.

Abstract

3-(4-[(3-Chlorophenyl)methoxy]phenyl)-5-[(methylamino)methyl]-2- oxazolidinone methanesulphonate (compound MD 780236) is a selective inhibitor of the B-form of monoamine oxidase. Inhibition involves an initial non-covalent interaction between enzyme and inhibitor followed by a time-dependent process resulting in irreversible inhibition. The initial, reversible, phase of inhibition was found to be competitive with respect to phenethylamine and 5-hydroxytryptamine, and a comparison of the Ki values indicated the affinity of the inhibitor for the B-form of the enzyme to be some 7-fold greater than its affinity for the A-form. This selectivity was considerably enhanced by preincubation of the enzyme and inhibitor. Time courses showed that complete inhibition was not achieved under conditions where the inhibitor concentration was over 100-fold greater than that of the enzyme. Assay of the activity of monoamine oxidase by determining the release of hydrogen peroxide fluorometrically showed compound MD 780236 to be a substrate for, as well as an inhibitor of, monoamine oxidase, and kinetic analysis revealed that the rate of product formation was some 530-fold greater than that of the process leading to irreversible inhibition of the B-form of the enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hydrogen Peroxide / metabolism
  • In Vitro Techniques
  • Isoenzymes / antagonists & inhibitors*
  • Kinetics
  • Male
  • Mitochondria, Liver / enzymology
  • Models, Biological
  • Monoamine Oxidase Inhibitors / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Oxazoles / metabolism
  • Oxazoles / pharmacology*
  • Oxazolidinones*
  • Oxidation-Reduction
  • Phenethylamines / metabolism
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism
  • Time Factors

Substances

  • Isoenzymes
  • Monoamine Oxidase Inhibitors
  • Oxazoles
  • Oxazolidinones
  • Phenethylamines
  • phenethylamine
  • Serotonin
  • MD 780236
  • Hydrogen Peroxide