Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B

In this paper we report on the in vitro and acute and chronic in vivo inhibitory activity of a highly potent and selective inhibitor of monoamine oxidase -B, rasagiline with structural similarity to selegiline (Sabbagh & Youdim, 1978; Kalir et al, 1981; see Figure 1

Moussa B H Youdim; Aviva Gross; John P M Finberg


Scholarcy highlights

  • The knowledge that dopamine is well oxidatively deaminated by monoamine oxidase types A and B, the dominance of MAO-B as compared to MAO-A in the extrapyramidal regions of human brain and the absence of thecheese reaction' in whole animal and isolated tissue preparations by the selective irreversible MAO-B inhibitor selegiline led to the introduction of selegiline as an adjunct to L-DOPA therapy of Parkinson's disease
  • The optical enantiomers of Npropargyl-1-aminoindan can be seen to possess a striking degree of stereoselectivity, since the-isomer is 1/3,800 as active as the-isomer for inhibition of MAO-B
  • There was no signi®cant di€erence between the IC50 values for rasagiline and selegiline for inhibition of MAO-A or MAO-B, and TVP 1022 was again seen to be largely devoid of inhibitory activity
  • The racemic form of N-propargyl-1aminoindan had approximately half the potency of rasagiline, indicating that no interaction occurred between the optical isomers at the MAO active site
  • In this paper we have examined the in vitro and in vivo MAOA and -B inactivating properties of rasagiline, the R(+) enantiomer of the selective irreversible MAO-B inhibitor AGN 1135, its S(7) enantiomer and the racemic compound AGN1135
  • The results demonstrate a high degree of stereoselectivity for MAO inhibition, in that the R(+) enantiomer was three orders of magnitude more e€ective in inhibition of MAO-B than the S(7) enantiomer
  • The present study has shown that rasagiline is a potent irreversible inhibitor of monoamine oxidase-B and it is 3 ± 15 times more potent than selegiline in the rat in vivo with a similar selectivity for inhibition of MAO-B to MAO-A

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