Interactions of 1-methyl-3-phenylpyrrolidine and 3-methyl-1-phenyl-3-azabicyclo[3.1.0]hexane with monoamine oxidase B

Anél Pretorius, Modupe O. Ogunrombi, Hendrik Fourie, Gisella Terre'Blanche, Neal Castagnoli, Jacobus J. Bergh, Jacobus P. Petzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


The parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its corresponding five-membered ring analogue 1-methyl-3-phenyl-3-pyrroline are cyclic tertiary allylamines and good substrates of monoamine oxidase B (MAO-B). The MAO-B catalyzed 2-electron α-carbon oxidation of this class of substrates appears to be dependent on the presence of the allylic π-bond since the corresponding saturated piperidinyl analogue of MPTP is reported not to be an MAO-B substrate. The only saturated cyclic tertiary amine known to act as an MAO-B substrate is the 3,4-cyclopropyl analogue of MPTP, 3-methyl-6-phenyl-3-azabicyclo[4.1.0]heptane. As part of our ongoing studies we have examined the MAO-B substrate properties of the corresponding pyrrolidinyl analogue, 1-methyl-3-phenylpyrrolidine, and the 3,4-cyclopropyl analogue, 3-methyl-1-phenyl-3-azabicyclo[3.1.0]hexane. The results document that both the pyrrolidinyl analogue [Km = 234 μM; Vmax = 8.37 nmol/(min-mg mitochondrial protein)] and the 3,4-cyclopropyl analogue [Km = 148 μM; Vmax = 16.9 nmol/(min-mg mitochondrial protein)] are substrates of baboon liver mitochondrial MAO-B. We also have compared the neurotoxic potential of these compounds in the C57BL/6 mouse. The results led us to conclude that these compounds are not MPTP-type neurotoxins.

Original languageEnglish
Pages (from-to)4111-4118
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number11
Publication statusPublished - 1 Jun 2010
Externally publishedYes


  • 1-Methyl-3-phenyl-3-pyrroline
  • 1-Methyl-3-phenylpyrrolidine
  • 3-Methyl-1-phenyl-3-azabicyclo[3.1.0]hexane
  • Monoamine oxidase B
  • Saturated substrate


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