0

The Effects of BMY-14802 Against L-DOPA- And Dopamine Agonist-Induced Dyskinesia in the Hemiparkinsonian Rat

Nirmal Bhide, David Lindenbach, Margaret A Surrena, Adam A Goldenberg, Christopher Bishop, S Paul Berger, Melanie A Paquette

Psychopharmacology (Berl). 2013 Jun;227(3):533-44.

PMID: 23389756

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP105565568 BMY-14802 BMY-14802 105565-56-8 Price
qrcode