Ropinirole Implants Reverse MPTP-Induced Parkinsonism in Rhesus Monkeys

Steven J.  Siegel; Lauren  Nagy; Torben  Skarsfeldt; Mark  Pierce; Carol O’  Neill; Robert  Lin; Lori  Langhamer; Jeffery H.  Kordower

doi:10.4236/pp.2013.43A001

Steven J. Siegel^*, Lauren Nagy, Torben Skarsfeldt, Mark Pierce, Carol O’ Neill, Robert Lin, Lori Langhamer, Jeffery H. Kordower

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.

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

Cite this paper: S. Siegel, L. Nagy, T. Skarsfeldt, M. Pierce, C. Neill, R. Lin, L. Langhamer and J. Kordower, "Ropinirole Implants Reverse MPTP-Induced Parkinsonism in Rhesus Monkeys," Pharmacology & Pharmacy, Vol. 4 No. 3, 2013, pp. 1-8. doi: 10.4236/pp.2013.43A001.

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