Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole

• Published in: Journal of Neural Transmission Vol. 104; no. 2-3; pp. 209 - 228
• Main Authors: CARVEY, P. M, PIERI, S, LING, Z. D
• Format: Journal Article
• Language: English
• Published: Wien Springer 01.01.1997; New York, NY
• Subjects: Animals; Antiparkinson Agents - antagonists & inhibitors; Antiparkinson Agents - toxicity; Benzothiazoles; Biological and medical sciences; Cell Count; Cell Survival - drug effects; Culture Media, Conditioned; Dopamine Agonists - pharmacology; Drug toxicity and drugs side effects treatment; Female; Immunohistochemistry; Levodopa - antagonists & inhibitors; Levodopa - toxicity; Medical sciences; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - enzymology; Neurons - drug effects; Neurons - enzymology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Stereoisomerism; Thiazoles - pharmacology; Toxicity: nervous system and muscle; Tyrosine 3-Monooxygenase - metabolism; Culture medium; Oxidative stress; Agonist; Rat; Toxicity; Rodentia; Central nervous system; Midbrain; Neuroprotective agent; Antiparkinson agent; Pramipexole; Vertebrata; Mammalia; D2 Dopamine receptor; Animal; Levodopa
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/bf01273182

The direct-acting dopamine (DA) agonist pramipexole (2 amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochlori de) 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 dose-dependent 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 heat-inactivation 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.