(S)-(-)-3-(3-(methylsulfonyl)phenyl)-1-propylpiperidine ((-)-OSU6162) is a 
phenylpiperidine derivative which exhibits low affinity to the dopamine D2 
receptor in vitro. However, in vivo, positron emission tomography scanning 
studies show that the compound displaces the selective dopamine D2 receptor 
antagonist, raclopride. We have evaluated, in this study, the effect of 
(-)-OSU6162, on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias in a 
primate model of Parkinson's disease. Five 
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys 
with a stable parkinsonian syndrome and reproducible dyskinesias to L-DOPA were 
used in this study. The monkeys were housed in observation cages equipped with 
an electronic motility monitoring system. They were injected subcutaneously 
(s.c.) with L-DOPA methyl ester (125 mg per animal) plus benserazide (50 mg per 
animal; L-DOPA/benserazide) alone or in combination with (-)-OSU6162 (1.0, 3.0, 
6.0 or 10 mg/kg, s.c.). Subcutaneous injection of sterile saline was used as 
control. L-DOPA/benserazide increased locomotion and improved parkinsonism but 
also induced dyskinesias. Co-administration of (-)-OSU6162 with 
L-DOPA/benserazide produced a significant reduction in L-DOPA-induced 
dyskinesias. This improvement in L-DOPA-induced dyskinesias occurred mainly at 
the onset of the L-DOPA/benserazide effect as reflected by an increase in the 
duration of the "ON" state without dyskinesias up to 3.4 fold after (-)-OSU6162 
co-administration as compared to L-DOPA/benserazide alone. The anti-dyskinetic 
effect of (-)-OSU6162 was maintained during 14 days and no tolerance to this 
effect was observed. Our data suggests that (-)-OSU6162 could be of significant 
clinical value to reduce L-DOPA-induced dyskinesias in fluctuating advanced 
Parkinson's disease patients.