Continuous administration of rotigotine to MPTP-treated common marmosets enhances anti-parkinsonian activity and reduces dyskinesia induction

Rotigotine is a novel, non-ergoline dopamine D-3/D-2/D-1-receptor agonist for the treatment of Parkinson's disease that can be Continuously delivered by the transdermal route to provide stable plasma levels. Continuous drug delivery should reduce the risk of dyskinesia induction in comparison to pulsatile dopaminergic treatment. Thus the aim of the study was to compare the reversal of motor disability and induction of dyskinesia produced by continuous compared to pulsatile rotigotine administration in MPTPtreated common marmosets. The study also investigated whether pulsatile or continuous rotigotine administration in combination with L-DOPA prevented L-DOPA-induced dyskinesia. Animals were treated for 28 days with vehicle or pulsatile (twice daily) or continuous delivery of rotigotine (via an osmotic minipump). Subsequently, L-DOPA was then co-administered for a further 28 days. Animals were assessed for locomotor activity, motor disability and dyskinesia induction. The study showed that both continuous and pulsatile administration of rotigotine improved motor deficits and normalized motor function in MPTPtreated monkeys. However, continuous rotigotine delivery reduced dyskinesia expression compared to pulsatile treatment. Both pulsatile and continuous rotigotine administration produced less dyskinesia than administration of L-DOPA alone. The addition of L-DOPA to either pulsatile or continuous rotigotine treatment resulted in the induction of marked dyskinesia similar to that produced by treatment with L-DOPA alone. These data further support the hypothesis that continuous delivery of a dopaminergic agent reduces the risk of dyskinesia induction. However, continuous rotigotine administration did not prevent L-DOPA from inducing dyskinesia suggesting that L-DOPA may induce dyskinesia by mechanisms different from dopamine agonist drugs. (C) 2009 Elsevier Inc. All rights reserved.Peer reviewe

Continuous vs pulsatile administration of rotigotine in rat and monkey models of Parkinson's disease: A comparison

Peer reviewe

Preclinical models of levodopa-induced dyskinesia

L -DOPA-induced dyskinesia (LID) represents one of the major limitations in the current pharmacotherapy of Parkinson's disease (PD) and affects the majority of PD patients. Animal models are the most important preclinical tool for molecular investigations of LID mechanisms and therapeutic targets. Over the last two decades, models of LID have been developed in both nonhuman primate and rodent species, recapitulating several aspects of the human dyskinesia. This chapter will review and compare the main features of the rodent and nonprimate models of LID currently available and summarize some of the main neurobiological fi ndings obtained from these models