ATTENUATION OF LEVODOPA-INDUCED TOXICITY IN MESENCEPHALIC CULTURES BYPRAMIPEXOLE

The direct-acting dopamine (DA) agonist pramipexole (2 hydro-6-propyl- amino-benzthiazole-dihydrochloride) was evaluated for its ability to a ttenuate 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 dose-depende nt and saturable fashion (ED50 = 500 pM), its inactive stereoisomer wa s significantly less potent in this regard and pergolide and bromocrip tine had negligible cytoprotective effects. Culture media from mesence phalic cultures incubated with pramipexole for 6 days increased THir c ell counts in freshly harvested recipient cultures. The magnitude of t his effect was directly proportional to the amount of pramipexole in t he donor cultures and heat-inactivation of the media abolished the gro wth promoting effect. The results from this exploratory set of experim ents suggest that pramipexole may be cytoprotective to dopamine neuron s in tissue culture. Pramipexole's affinity for DA receptors, its anti oxidant action or its ability to enhance mesencephalic trophic activit y could be responsible for this effect.