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The effects of BMY-14802 against L-DOPA- and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat.
MedLine Citation:
PMID:  23389756     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
RATIONALE: L-DOPA continues to be the primary treatment for patients with Parkinson's disease; however, the benefits of long-term treatment are often accompanied by debilitating side effects known as dyskinesias. In recent years, several 5-HT(1A) receptor agonists have been found to reduce dyskinesia in clinical and experimental models of PD. The purported sigma-1 antagonist, BMY-14802 has been previously demonstrated to reduce L-DOPA induced dyskinesia in a 5-HT(1A) receptor dependent manner. OBJECTIVE: In the present study, we extend these findings by examining the anti-dyskinetic potential of BMY-14802 against L-DOPA, the D(1) receptor agonist SKF81297 and the D(2) receptor agonist, quinpirole, in the hemi-parkinsonian rat model. In addition, the receptor specificity of BMY-14802's effects was evaluated using WAY-100635, a 5-HT(1A) receptor antagonist. RESULTS: Results confirmed the dose-dependent (20 > 10 > 5 mg/kg) anti-dyskinetic effects of BMY-14802 against L-DOPA with preservation of anti-parkinsonian efficacy at 10 mg/kg. BMY-14802 at 10 and 20 mg/kg also reduced dyskinesia induced by both D(1) and D(2) receptor agonists. Additionally, BMY-14802's anti-dyskinetic effects against L-DOPA, but not SKF81297 or quinpirole, were reversed by WAY-100635 (0.5 mg/kg). CONCLUSION: Collectively, these findings demonstrate that BMY-14802 provides anti-dyskinetic relief against L-DOPA and direct DA agonist in a preclinical model of PD, acting via multiple receptor systems and supports the utility of such compounds for the improved treatment of PD.
Authors:
Nirmal Bhide; David Lindenbach; Margaret A Surrena; Adam A Goldenberg; Christopher Bishop; S Paul Berger; Melanie A Paquette
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-7
Journal Detail:
Title:  Psychopharmacology     Volume:  -     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, 13902-6000, NY, USA.
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