title: The effects of BMY-14802 against L-DOPA- and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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: Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902-6000, USA.
authors: Nirmal
authors: N
authors: Bhide
authors: David
authors: D
authors: Lindenbach
authors: Margaret A
authors: MA
authors: Surrena
authors: Adam A
authors: AA
authors: Goldenberg
authors: Christopher
authors: C
authors: Bishop
authors: S Paul
authors: SP
authors: Berger
authors: Melanie A
authors: MA
authors: Paquette
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011743:Pyrimidines; D017447:Receptors, Dopamine D1; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D044282:Receptor, Serotonin, 5-HT1A; D007980:Levodopa
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