Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole.
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.
Ferrari-Toninelli
Giulia
G
Department of Biomedical Sciences and Biotechnologies and National Institute of Neuroscience, University of Brescia, Brescia, Italy.
Maccarinelli
Giuseppina
G
Uberti
Daniela
D
Buerger
Erich
E
Memo
Maurizio
M
D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000008:administration & dosage*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D018492:Dopamine Antagonists / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D000077487:Pramipexole; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D052160:Benzothiazoles; D018492:Dopamine Antagonists; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077487:Pramipexole; D006861:Hydrogen Peroxide