| The effects of BMY-14802 against L-DOPA- and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat. | |
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MedLine Citation:
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PMID: 23389756 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Nirmal Bhide; David Lindenbach; Margaret A Surrena; Adam A Goldenberg; Christopher Bishop; S Paul Berger; Melanie A Paquette |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-2-7 |
Journal Detail:
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Title: Psychopharmacology Volume: - ISSN: 1432-2072 ISO Abbreviation: Psychopharmacology (Berl.) Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-2-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7608025 Medline TA: Psychopharmacology (Berl) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, 13902-6000, NY, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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