Antiparkinsonian effect of a new selective adenosine A(2A) receptor antagonist in MPTP-treated monkeys

Richard Grondin, Paul J. Bédard, A. Hadj Tahar, L. Grégoire, A. Mori, H. Kase

Research output: Contribution to journalArticlepeer-review

244 Scopus citations

Abstract

Background: Chronic treatment with L-3,4-dihydroxyphenylalanine (L- dopa) is often associated with motor side effects in PD patients. The search for new therapeutic approaches has led to study the role of other neuromodulators including adenosine. Among the four adenosine receptors characterized so far, the A(2A) subtype is distinctively present on striatopallidal output neurons containing enkephalin and mainly bearing dopamine (DA) D2 receptors (indirect pathway). Studies in DA-denervated rats suggest that blockade of adenosine A(2A) receptors might be used in PD. Objective: To evaluate the antiparkinsonian effect of a new selective adenosine A(2A) receptor antagonist, KW-6002, in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated monkeys. Methods: In the present study, we used six MPTP-exposed cynomolgus monkeys already primed and exhibiting L- dopa-induced dyskinesias to evaluate both the antiparkinsonian and dyskinetic effect upon challenge with two oral doses (60 and 90 mg/kg) of KW-6002 administered alone or in combination with L-dopa/benserazide (50/12.5 mg). Results: KW-6002 administered alone produced a dose-dependent antiparkinsonian response that reached the level of efficacy of L- dopa/benserazide but was less likely to reproduce dyskinesias in these animals. When co-administered, KW-6002 potentiated the effects of L- dopa/benserazide on motor activity (up to 30%) without affecting the dyskinetic response. Conclusion: Adenosine A(2A) receptor antagonists have antiparkinsonian effects of their own with a reduced propensity to elicit dyskinesias. They might therefore be useful agents in the treatment of PD.

Original languageEnglish
Pages (from-to)1673-1677
Number of pages5
JournalNeurology
Volume52
Issue number8
DOIs
StatePublished - May 12 1999

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint

Dive into the research topics of 'Antiparkinsonian effect of a new selective adenosine A(2A) receptor antagonist in MPTP-treated monkeys'. Together they form a unique fingerprint.

Cite this