Repeated administration of piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: a behavioural and biochemical investigation

Mov Disord. 2002 Sep;17(5):887-901. doi: 10.1002/mds.10200.


Piribedil ([1-(3,4-methylenedioxybenzyl)-4-(2-pyrimidinyl)piperazine]; S 4200) is a dopamine agonist with equal affinity for D(2)/D(3) dopamine receptors effective in treating Parkinson's disease as monotherapy or as an adjunct to levodopa (L-dopa). However, its ability to prime basal ganglia for the appearance of dyskinesia is unknown. We now report on the ability of repeated administration of piribedil to induce dyskinesia in drug naïve 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -lesioned common marmosets compared with L-dopa and its actions on the direct and indirect striatal outflow pathways. Administration of piribedil (4.0-5.0 mg/kg orally) or L-dopa (12.5 mg/kg orally plus carbidopa 12.5 mg/kg orally twice daily) produced equivalent increases in locomotor activity and reversal of motor deficits over a 28-day study period. Administration of L-dopa resulted in the progressive development of marked dyskinesia over the period of study. In contrast, administration of piribedil produced a significantly lower degree and intensity of dyskinesia. Surprisingly, piribedil caused an increase in vigilance and alertness compared to L-dopa, which may relate to the recently discovered alpha(2)-noradrenergic antagonist properties of piribedil. The behavioural differences between piribedil and L-dopa are reflected in the biochemical changes associated with the direct striatal output pathway. Administration of L-dopa or piribedil did not reverse the MPTP-induced up-regulation of preproenkephalin A mRNA in rostral or caudal areas of the putamen or caudate nucleus. In contrast, administration of either piribedil or L-dopa reversed the downregulation of preprotachykinin mRNA induced by MPTP in rostral and caudal striatum. L-dopa, but not Piribedil, reversed the decrease in preproenkephalin B mRNA produced by MPTP treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects*
  • Animals
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / therapeutic use*
  • Arousal / drug effects
  • Callithrix
  • Caudate Nucleus / metabolism
  • Corpus Striatum / metabolism
  • Culture Techniques
  • Drug Administration Schedule
  • Dyskinesia, Drug-Induced / etiology*
  • Dyskinesias / diagnosis*
  • Dyskinesias / drug therapy*
  • Dyskinesias / metabolism
  • Female
  • In Situ Hybridization
  • Levodopa / adverse effects*
  • Locomotion / drug effects
  • Male
  • Piribedil / administration & dosage
  • Piribedil / adverse effects
  • Piribedil / therapeutic use*
  • RNA, Messenger / metabolism
  • Severity of Illness Index
  • Time Factors


  • Antiparkinson Agents
  • RNA, Messenger
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Piribedil