Document Detail


The effects of BMY-14802 against L-DOPA- and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat.
MedLine Citation:
PMID:  23389756     Owner:  NLM     Status:  MEDLINE    
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-HT1A 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-HT1A 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 D1 receptor agonist SKF81297 and the D2 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-HT1A 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 D1 and D2 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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-07
Journal Detail:
Title:  Psychopharmacology     Volume:  227     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-16     Completed Date:  2013-12-13     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  533-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiparkinson Agents / administration & dosage,  adverse effects*,  therapeutic use
Disease Models, Animal
Dopamine Agonists / administration & dosage,  adverse effects*,  therapeutic use
Dyskinesia, Drug-Induced / drug therapy*,  etiology
Levodopa / administration & dosage,  adverse effects*,  therapeutic use
Male
Motor Activity / drug effects
Parkinson Disease / drug therapy*
Pyrimidines / administration & dosage,  pharmacology,  therapeutic use*
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A / metabolism
Receptors, Dopamine D1 / metabolism
Grant Support
ID/Acronym/Agency:
1R43NS064706/NS/NINDS NIH HHS; R01 NS059600/NS/NINDS NIH HHS; R01-NS059600/NS/NINDS NIH HHS; R43 NS064706/NS/NINDS NIH HHS; T32 DA007262/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Antiparkinson Agents; 0/Dopamine Agonists; 0/Pyrimidines; 0/Receptors, Dopamine D1; 105565-56-8/alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; 112692-38-3/Receptor, Serotonin, 5-HT1A; 46627O600J/Levodopa
Comments/Corrections

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