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Open Access Highly Accessed Research article

Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole

Giulia Ferrari-Toninelli1, Giuseppina Maccarinelli1, Daniela Uberti1, Erich Buerger2 and Maurizio Memo1*

Author Affiliations

1 Department of Biomedical Sciences and Biotechnologies and National Institute of Neuroscience, University of Brescia, Brescia, Italy

2 Department of Central Nervous System Research, Boehringer-Ingelheim Pharma, Biberach an der Riss, Germany

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BMC Pharmacology 2010, 10:2  doi:10.1186/1471-2210-10-2

Published: 5 February 2010

Abstract

Background

Pramipexole exists as two isomers. The S(-) enantiomer is a potent D3/D2 receptor agonist and is extensively used in the management of PD. In contrast, the R(+) enantiomer is virtually devoid of any of the DA agonist effects. Very limited studies are available to characterize the pharmacological spectrum of the R(+) enantiomer of pramipexole.

Results

Using differentiated SH-SY5Y neuroblastoma cells as an experimental model, here we show that S(-) and R(+) pramipexole are endowed with equipotent efficacy in preventing cell death induced by H2O2 and inhibiting mitochondrial reactive oxygen species generation. Both pramipexole enantiomers prevented mitochondrial ROS generation with a potency about ten times higher then that elicited for neuroprotection.

Conclusions

These results support the concept of both S(-) and R(+) pramipexole enantiomers as mitochondria-targeted antioxidants and suggest that the antioxidant, neuroprotective activity of these drugs is independent of both the chiral 6-propylamino group in the pramipexole molecule and the DA receptor stimulation.