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  • Title: The dopamine agonist piribedil with L-DOPA improves attentional dysfunction: relevance for Parkinson's disease.
    Author: Turle-Lorenzo N, Maurin B, Puma C, Chezaubernard C, Morain P, Baunez C, Nieoullon A, Amalric M.
    Journal: J Pharmacol Exp Ther; 2006 Nov; 319(2):914-23. PubMed ID: 16920993.
    Abstract:
    Cognitive deficits are often associated with motor symptoms in Parkinson's disease. This study investigates the ability of piribedil ([(methylenedioxy-3,4 benzyl)-4 pyperazinyl-1]-2 pyrimidine), a D(2)/D(3) dopamine (DA) receptor agonist with antagonist activity at alpha(2A)-adrenoceptors, to restore motor and attentional deficits in nigrostriatal 6-hydroxydopamine-lesioned rats. Subjects were trained to depress a lever, detect a stimulus occurring after variable foreperiods, and release the lever quickly afterward. Striatal DA depletions produce deficits in the timing of foreperiods and prolong reaction times. Although a subchronic treatment with piribedil (0.1-2 mg/kg) is not effective, a dose of 0.3 mg/kg administered for 3 weeks significantly reverses the akinetic deficits produced by the striatal dopamine depletion and progressively improves attentional deficits. When coadministered with the dopamine prodrug l-3,4-dihydroxyphenylalanine (l-DOPA) (3 mg/kg), piribedil (0.3 mg/kg) promotes a rapid and full recovery of preoperative performance. These results suggest that administration of l-DOPA in combination with piribedil in a chronic treatment as either initial or supplemental therapy for Parkinson's disease might improve cognitive functions while reducing the risk for motor complications.
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