Pramipexole combined with levodopa improves motor function but reduces dyskinesia in MPTP-treated common marmosets.

Abstract

Reduced expression of dyskinesia is observed in levodopa-primed MPTP-treated common marmosets when dopamine agonists are used to replace levodopa. We now investigate whether a combination of the D-2/D-3 agonist pramipexole and levodopa also reduces dyskinesia intensity while maintaining the reversal of motor disability. Drug naïve, non-dyskinetic MPTP-treated common marmosets were treated daily for up to 62 days with levodopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o. BID) or pramipexole (0.04-0.3 mg/kg BID) producing equivalent reversal of motor disability and increases in locomotor activity. Levodopa alone resulted in marked dyskinesia induction but little or no dyskinesia resulted from the administration of pramipexole. From day 36, some animals were treated with a combination of levodopa (3.125-6.25 mg/kg plus carbidopa 12.5 mg/kg p.o. BID) and pramipexole (0.1-0.2 mg/kg p.o. SID). This improved motor disability to a greater extent than occurred with levodopa alone. Importantly, while dyskinesia was greater than that produced by pramipexole alone, the combination resulted in less intense dyskinesia than produced by levodopa alone. These results suggest that pramipexole could be administered with a reduced dose of levodopa to minimize dyskinesia in Parkinson's disease while maintaining therapeutic efficacy.