(-)-OSU 6162 inhibits levodopa-induced dyskinesias in a monkey model of Parkinson's disease

Neuroreport. 1997 Jul 28;8(11):2567-70. doi: 10.1097/00001756-199707280-00029.

Abstract

We have studied the effects of two D2 dopamine receptor-selective compounds, (-)-OSU 6162 and raclopride, on levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmosets (Callithrix jacchus). Three monkeys developed a severe parkinsonian syndrome following administration of MPTP. In response to daily levodopa treatment the animals developed reproducible and idiosyncratic peak-dose dyskinesias. Pretreatment with (-)-OSU 6162 and raclopride, in doses increased by multiples of three, both dose-dependently relieved the levodopa-induced dyskinesias. However, in contrast to when raclopride pretreatment was given, (-)-OSU 6162 pretreatment did not induce akinesia. Our investigation suggests that (-)-OSU 6162 may be useful an an adjuvant treatment to levodopa in advanced Parkinson's disease to selectively combat levodopa-induced dyskinesias without affecting the antiparkinsonian response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Callithrix
  • Carbidopa / therapeutic use
  • Dopamine Antagonists / pharmacology
  • Levodopa / adverse effects*
  • Levodopa / antagonists & inhibitors
  • Male
  • Motor Activity / drug effects*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy
  • Parkinson Disease, Secondary / physiopathology*
  • Piperidines / pharmacology*
  • Posture
  • Raclopride
  • Salicylamides / pharmacology

Substances

  • Dopamine Antagonists
  • Piperidines
  • Salicylamides
  • OSU 6162
  • Raclopride
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Carbidopa