Titolo:  A preclinical study on the combined effects of repeated eltoprazine and preladenant treatment for alleviating L-DOPA-induced dyskinesia in Parkinson's disease
Data di pubblicazione:  2017
Autori:  Ko, Wai Kin D.; Li, Qin; Cheng, Long Yun; Morelli, Micaela; Carta, Manolo; Bezard, Erwan
Numero degli autori:  6
Lingua:  Inglese
Presenza coautori internazionali: 
Volume:  813
Pagina iniziale:  10
Pagina finale:  16
Numero di pagine:  7
Digital Object Identifier (DOI):  http://dx.doi.org/10.1016/j.ejphar.2017.07.030
Codice identificativo Pubmed:  28739086
Codice identificativo Scopus:  2-s2.0-85025643315
Codice identificativo ISI:  WOS:000410883400002
URL:  www.elsevier.com/locate/ejphar
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 –parkinsonian 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.
Parole chiave:  5-HT; Adenosine; L-DOPA-induced dyskinesia; Parkinson's disease; Pharmacology
Tipologia: 1.1 Articolo in rivista

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