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Ropinirole Implants Reverse MPTP-Induced Parkinsonism in Rhesus Monkeys

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Author(s): Steven J. Siegel | Lauren Nagy | Torben Skarsfeldt | Mark Pierce | Carol O’ Neill | Robert Lin | Lori Langhamer | Jeffery H. Kordower

Journal: Pharmacology & Pharmacy
ISSN 2157-9423

Volume: 04;
Issue: 03;
Start page: 1;
Date: 2013;
Original page

Keywords: Ropinirole | Implant | Parkinson’s Disease | MPTP | Pharmacokinetic | Dyskinesia

ABSTRACT
Purpose: We compared efficacy and side effects of ropinirole implants with oral ropinirole in parkinsonian monkeys. Methods: Twenty monkeys received injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP) to render them parkinsonian. Monkeys were then placed into 3 groups based upon clinical rating scores (CRS). Group 1 received oral ropinirole and placebo implants. Group 2 receivedropinirole implants that released 1/9th of the animals’ optimal daily oral dose and oral placebo. Group 3 received placebo implants and oral placebo. Monkeys were assessed for pharmacokinetic data, CRS, Global Dyskinesia Rating Scale, and skin irritation. Results: For the ropinirole implant group, the activity pattern was similar to that seen pre-MPTP; which extended through the weekends and was greater than control treated parkinsonian monkeys. Oral ropinirole yielded a high degree of variability for activity, with values following oral dosing being higher than the pre-MPTP periodbut levels similar to placebo treated parkinsonian animals during weekends, which were excluded from oral dosing. Implants and oral treatment achieved significant improvement in CRS between 11 - 60 days and 4 - 60 days respectively. Conclusion: Low dose ropinirole implants have the potential to provide continuous clinical improvement in bradykinesia with fewer “off periods” and lower risk for medication-induced psychosis than oral medication.
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