Novel therapeutic strategy for the control of dyskinesia in the therapy of Parkinson's disease (Abstract/Poster in convegno)

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  • Novel therapeutic strategy for the control of dyskinesia in the therapy of Parkinson's disease (Abstract/Poster in convegno) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • Pinna A. (1,2), Costa G. (2), Simola N. (2), Frau L. (2), Tronci E. (2), Carta M. (2), Morelli M. (1,2) (2014)
    Novel therapeutic strategy for the control of dyskinesia in the therapy of Parkinson's disease
    in 9th FENS Forum of Neuroscience, Milano, 5-9 Luglio
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Pinna A. (1,2), Costa G. (2), Simola N. (2), Frau L. (2), Tronci E. (2), Carta M. (2), Morelli M. (1,2) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://fens2014.meetingxpert.net/FENS_427/poster_103573/program.aspx (literal)
Note
  • Poster (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • (1) CNR Institute of Neuroscience, Cagliari, Italy; (2) Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy (literal)
Titolo
  • Novel therapeutic strategy for the control of dyskinesia in the therapy of Parkinson's disease (literal)
Abstract
  • Recent report demonstrated that mixed serotonin 5-HT1A/B receptor agonist, eltoprazine, produces a near to full suppression of dyskinetic-like behaviors in animal models of Parkinson's disease (PD). However, eltoprazine resulted in a partial reduction of motility induced by L-DOPA, both in rats and in monkeys. Moreover, in a recent clinical trial, the partial 5-HT1A agonist sarizotan has been found to be only partially effective. Preclinical and clinical studies showed that adenosine A2A receptor antagonists significantly increase L-DOPA efficacy in PD, without exacerbating dyskinetic-like behaviors. Preladenant, an A2A receptor antagonist utilized in clinical trials, is an excellent tool for assessing the role of A2A receptors in movement disorders. On this basis, we hypothesize that combination of eltoprazine with preladenant may produce suppression of L-DOPA-induced dyskinesia, without impairing the efficacy of L-DOPA in relieving motor symptoms. Unilateral 6-hydroxydopamine-lesioned rats, rendered dyskinetic by repeated-L-DOPA-treatment, were administered with eltoprazine (0.3 or 0.6 mg/kg) and preladenant (0.3 or 1 mg/kg), singularly or in combination with L-DOPA (4 or 6 mg/kg), and rotational behavior, as index of motility, and abnormal involuntary movements (AIMs) as index of dyskinesia, were evaluated. Results show that combined administration of L-DOPA (4mg/kg) plus eltoprazine (0.6mg/kg) plus preladenant (0.3mg/kg) significantly reduced dyskinetic-like behaviors, as revealed by AIMs test without impairing the motor activity, as revealed by similar number of contralateral and ipsilateral rotations. Overall these data suggest that combination of L-DOPA (4mg/kg) with eltoprazine (0.6mg/kg) and preladenant (0.3mg/kg) could be a new therapeutic strategy for treating motor symptoms and dyskinesia in PD. (literal)
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