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

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Abstract
Piribedil ([1‐(3,4‐methylenedioxybenzyl)‐4‐(2‐pyrimidinyl)piperazine]; S 4200) is a dopamine agonist with equal affinity for D2/D3 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 α2‐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. © 2002 Movement Disorder Society

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