Inactivation of purified human recombinant monoamine oxidases A and B by rasagiline and its analogues

J Med Chem. 2004 Mar 25;47(7):1760-6. doi: 10.1021/jm0310885.


The inactivation of purified human recombinant monoamine oxidases (MAO) A and B by rasagiline [N-propargyl-1(R)-aminoindan] and four of its analogues [N-propargyl-1(S)-aminoindan (S-PAI), 6-hydroxy-N-propargyl-1(R)-aminoindan (R-HPAI), N-methyl-N-propargyl-1(R)-aminoindan (R-MPAI), and 6-(N-methyl-N-ethyl carbamoyloxy)-N-propargyl-1(R)-aminoindan (R-CPAI)] has been investigated. All compounds tested, with the exception of R-CPAI, form stoichiometric N(5) flavocyanine adducts with the FAD moiety of either enzyme. No H(2)O(2) is produced during either MAO A or MAO B inactivation, which demonstrates that covalent addition occurs in a single turnover. Rasagiline has the highest specificity for MAO B, as demonstrated by a 100-fold higher inhibition potency (k(inact)/K(i)) compared to MAO A, with the remaining compounds exhibiting lower isozyme specificities. MAO B and MAO A are more selective for the R-enantiomer (rasagiline) compared to the S-enantiomer (S-PAI) by 2500-fold and 17-fold, respectively. Differences in UV/vis and CD spectral data of the complexes of the studied compounds with both MAO A and MAO B are interpreted in light of crystallographic data of complexes of MAO B with rasagiline and its analogues (Binda, C.; et al. J. Med. Chem. 2004, 47, 1767-1774.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkynes / chemistry*
  • Circular Dichroism
  • Humans
  • Indans / chemistry*
  • Kinetics
  • Monoamine Oxidase / chemistry*
  • Monoamine Oxidase / isolation & purification
  • Monoamine Oxidase Inhibitors / chemistry*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Spectrometry, Mass, Electrospray Ionization
  • Stereoisomerism
  • Structure-Activity Relationship


  • Alkynes
  • Indans
  • Monoamine Oxidase Inhibitors
  • Recombinant Proteins
  • rasagiline
  • Monoamine Oxidase