title: 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.
authors.affiliation: Neurodegenerative Diseases Research Centre, School of Health and Biomedical Sciences, King's College London, London, United Kingdom.
authors.forename: Kayhan A
authors.initials: KA
authors.lastname: Tayarani-Binazir
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Sarah
authors.initials: S
authors.lastname: Rose
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
authors.forename: Peter
authors.initials: P
authors.lastname: Jenner
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000627:therapeutic use*; D002144:Callithrix; D002230:Carbidopa / Q000627:therapeutic use; D004185:Disability Evaluation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D020820:Dyskinesias / Q000188:drug therapy* / Q000209:etiology*; D007980:Levodopa / Q000627:therapeutic use*; D020267:MPTP Poisoning / Q000150:complications*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D000077487:Pramipexole; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D007980:Levodopa; D000077487:Pramipexole; D002230:Carbidopa