TITLE:
Ropinirole Implants Reverse MPTP-Induced Parkinsonism in Rhesus Monkeys
AUTHORS:
Steven J. Siegel, Lauren Nagy, Torben Skarsfeldt, Mark Pierce, Carol O’ Neill, Robert Lin, Lori Langhamer, Jeffery H. Kordower
KEYWORDS:
Ropinirole; Implant; Parkinson’s Disease; MPTP; Pharmacokinetic; Dyskinesia
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.4 No.3A,
June
24,
2013
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.