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

Movement Disorders : Official Journal of the Movement Disorder Society
K Tayarani-BinazirP Jenner

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 t...Continue Reading

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Citations

Dec 14, 2011·The Neurologist·Maria Cruz Rodriguez-OrozOriol de Fabregues
Jan 10, 2012·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·O Gershanik, P Jenner
Dec 10, 2013·Expert Opinion on Investigational Drugs·Fabio Blandini, Marie-Therese Armentero
Mar 11, 2018·The Journal of Pharmacology and Experimental Therapeutics·Nicolas VeyresPhilippe Huot
Jan 16, 2013·Pharmacological Reviews·Philippe HuotJonathan M Brotchie
Sep 15, 2020·Experimental Neurobiology·Joshua A BlosserDaewoo Lee

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