A preclinical study on the combined effects of repeated eltoprazine and preladenant treatment for alleviating L-DOPA-induced dyskinesia in Parkinson's disease
Morelli, Micaela;Carta, Manolo;
2017-01-01
Abstract
Eltoprazine, a serotonergic (5-HT)1A/Breceptor agonist, is a potential treatment for L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD) but notably compromises the anti-parkinsonian effects of L-DOPA, as seen in rodent and monkey models of PD. Preladenant, a selective adenosine A2areceptor antagonist, mediates modest anti-parkinsonian effects in parkinsonian monkeys. In a recent investigation, combined eltoprazine and preladenant treatment with a sub-threshold dose of L-DOPA acutely attenuated dyskinesia without exacerbating PD disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. The aim of this study was to investigate the daily repeated treatment effects of eltoprazine (1 mg/kg) alone, and in combination with preladenant (5 mg/kg), on the motor symptoms of PD and LID in MPTP-treated macaques. The anti-dyskinetic and âparkinsonian effects of combinative drug administration with a sub-threshold dose of L-DOPA were measured over 14 days. Eltoprazine treatment alone produced a near-complete suppression of dyskinesia but consistently increased parkinsonism. The administration of preladenant with eltoprazine prevented the increased severity of parkinsonian motor symptoms but was unable to maintain a reduced expression of dyskinesia with repeated administration. These data demonstrate the clinical utility of the modulation of the serotonergic and adenosine neurotransmitter systems with selective pharmacological agents for only acute treatment of LID. This multi-targeted approach is unsuitable as a long-term treatment regimen due to unsustainable therapeutic effects on dyskinesia.File | Size | Format | |
---|---|---|---|
Ko et al_Eur Jour Neurosci 2017.pdf Solo gestori archivio
Type: versione editoriale
Size 731.32 kB
Format Adobe PDF
|
731.32 kB | Adobe PDF | & nbsp; View / Open Request a copy |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.