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

Clinical pharmacology and efficacy of rotigotine (Neupro® patch) in the treatment of restless leg syndrome

“…The increased contraversive turning by both compounds indicated a post-synaptic activity [26]. This finding is further supported by another study showing that both continuous and pulsatile administration of rotigotine improved motor deficits and normalized motor function in MPTP-treated monkeys [27].…”

The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease

“…Perhaps quite surprisingly though, in the MPTP-lesioned marmoset, de novo administration of apomorphine or pergolide led to dyskinesia of the same severity . De novo continuous administration of the dopamine receptor agonists apomorphine and rotigotine induced less dyskinesia than de novo once or twice daily administration of these drugs in the MPTP-lesioned NHP (Bibbiani et al, 2005a;Stockwell et al, 2009). Moreover, in the MPTP-lesioned NHP, continuous administration of rotigotine alleviated dyskinesia induced by chronic pulsatile therapy with rotigotine or L-DOPA (Stockwell et al, 2010).…”

New Approaches to Therapy

“…It is certainly true that the longer acting oral dopamine agonists used clinically to treat PD produce less dyskinesia than equivalent doses of L-DOPA in this model. However, short-acting dopamine agonists, such as rotigotine administered by subcutaneous injection, also result in much less dyskinesia and overall there seems to be no correlation with plasma half-life or duration of effect (Stockwell et al, 2009). This takes the argument back to the previous discussion that the difference lies in the pharmacology of L-DOPA and dopamine agonists and not in their pharmacokinetics.…”

“…Two broad approaches to this issue have evolved showing that it applies equally to L-DOPA and dopamine agonists. A series of studies in MPTP-treated primates showed that the continuous delivery of D2/D3 selective dopamine agonists by continuous subcutaneous infusion results in even lower levels of dyskinesia than seen on repeated oral administration or subcutaneous injection (Bibbiani et al, 2005b;Stockwell et al, 2008;Stockwell et al, 2009). For example, continuous 24 h subcutaneous infusion of rotigotine using osmotic minipumps was used to achieve steady-state plasma levels and mimic delivery from a transdermal patch in man.…”