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The interactions of monoamine oxidase with some derivatives of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

  • J. P. Sullivan
  • K. F. Tipton
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 29)

Summary

The interactions of a number of derivatives of the dopaminergic neurotoxin MPTP (l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) with monoamine oxidase (MAO) have been studied. The desmethyl derivative, 4-phenyl-1,2,3,6-tetrahydropyridine (PTP), was oxidised by MAO-B to form the corresponding dihydropyridine. Initial interaction with both forms of MAO was competitive. However the degree of inhibition of MAO-B, but not MAO-A, increased with time and became irreversible. Substitution of a methyl group at the 6-position of the heterocyclic ring of MPTP prevented it from acting as a substrate for MAO-B and greatly decreased its potency as an inhibitor of that form of MAO, although it remained a good competitive inhibitor of MAO-A. Replacement of the tetrahydropyridine ring of PTP by piperidine apparently abolished the ability to act as a substrate for MAO-B. The compound was however a competitive inhibitor of both forms of MAO. Substitution of a 3-(chlorophenyl)-methoxy-group at the 4’-position of this compound and PTP led to compounds which appeared to be devoid of substrate activity although they were potent, highly-selective, time-dependent inhibitors of MAO-B.

Keywords

Monoamine Oxidase Irreversible Inhibitor Dihydropyridine Derivative Tetrahydropyridine Ring Brain Monoamine Oxidase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • J. P. Sullivan
    • 1
  • K. F. Tipton
    • 1
    • 2
  1. 1.Department of BiochemistryTrinity CollegeDublinIreland
  2. 2.Department of BiochemistryTrinity CollegeDublin 2Ireland

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