Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B
Article first published online: 29 JAN 2009
2001 British Pharmacological Society
British Journal of Pharmacology
Volume 132, Issue 2, pages 500–506, January 2001
How to Cite
Youdim, M. B. H., Gross, A. and Finberg, J. P. M. (2001), Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. British Journal of Pharmacology, 132: 500–506. doi: 10.1038/sj.bjp.0703826
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received June 19, 2000, Revised October 26, 2000, Accepted November 2, 2000)
- Monoamine oxidase (MAO) A and B;
- small intestine;
- selegiline (l-deprenyl);
- irreversible inhibitors;
- Parkinson's disease;
Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(−)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, liver and small intestine.
While rasagiline and AGN1135 are highly potent selective irreversible inhibitors of MAO in vitro and in vivo, the S(−) enantiomer is relatively inactive in the tissues examined.
The in vitro IC50 values for inhibition of rat brain MAO activity by rasagiline are 4.43±0.92 nM (type B), and 412±123 nM (type A). The ED50 values for ex vivo inhibition of MAO in the brain and liver by a single dose of rasagiline are 0.1±0.01, 0.042±0.0045 mg kg−1 respectively for MAO-B, and 6.48±0.81, 2.38±0.35 mg kg−1 respectively for MAO-A.
Selective MAO-B inhibition in the liver and brain was maintained on chronic (21 days) oral dosage with ED50 values of 0.014±0.002 and 0.013±0.001 mg kg−1 respectively.
The degree of selectivity of rasagiline for inhibition of MAO-B as opposed to MAO-A was similar to that of selegiline. Rasagiline was three to 15 times more potent than selegiline for inhibition of MAO-B in rat brain and liver in vivo on acute and chronic administration, but had similar potency in vitro.
These data together with lack of tyramine sympathomimetic potentiation by rasagiline, at selective MAO-B inhibitory dosage, indicate that this inhibitor like selegiline may be a useful agent in the treatment of Parkinson's disease in either symptomatic or L-DOPA adjunct therapy, but lack of amphetamine-like metabolites could present a therapeutic advantage for rasagiline.
British Journal of Pharmacology (2001) 132, 500–506; doi:10.1038/sj.bjp.0703826