Journal of Neural Transmission

, Volume 104, Issue 2–3, pp 209–228

Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole

  • P. M. Carvey
  • S. Pieri
  • Z. D. Ling
Parkinson's Disease and Allied Conditions

Summary

The direct-acting dopamine (DA) agonist pramipexole (2 amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrocfiloride) was evaluated for its ability to attenuate levodopa-induced loss of tyrosine hydroxylase immunoreactive (THir, a marker for dopamine neurons) cells in mesencephalic cultures. Pramipexole reduced levodopa-induced THir cell loss in a dosedependent and saturable fashion (ED50=500 pM), its inactive stereoisomer was significantly less potent in this regard and pergolide and bromocriptine had negligible cytoprotective effects. Culture media from mesencephalic cultures incubated with pramipexole for 6 days increased THir cell counts in freshly harvested recipient cultures. The magnitude of this effect was directly proportional to the amount of pramipexole in the donor cultures and heatinactivation of the media abolished the growth promoting effect. The results from this exploratory set of experiments suggest that pramipexole may be cytoprotective to dopamine neurons in tissue culture. Pramipexole's affinity for DA receptors, its antioxidant action or its ability to enhance mesencephalic trophic activity could be responsible for this effect.

Keywords

Pramipexole mesencephalic cultures levodopa toxicity pergolide bromocriptine trophic factor oxidant stress neuroprotection 

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Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • P. M. Carvey
    • 1
  • S. Pieri
    • 1
  • Z. D. Ling
    • 1
  1. 1.Neuropharmacology Research Laboratories, and Research Center for Brain Repair, Departments of Neurological Sciences and PharmacologyRush-Presbyterian-St. Luke's Medical CenterChicagoUSA

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