Objective: To evaluate the pharmacology, pharmacokinetics, clinical efficacy, and tolerability of rotigotine, a nonergoline D(3)/D(2)/D(1) dopamine receptor agonist in the treatment of Parkinson's disease and restless legs syndrome (RLS).

Data sources: A literature search was conducted using MEDLINE (1996-December 2006) and International Pharmaceutical Abstracts, using the search terms rotigotine and dopamine agonist. References cited in the articles were reviewed for additional information. Information was also obtained from Schwarz Pharma. Abstracts for posters at scientific conferences were accessed from conference Web sites.

Study selection and data extraction: English-language literature reporting controlled animal and human clinical studies was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of rotigotine. Clinical trials selected for inclusion were limited to those with human subjects; data from animal studies were included if human data were not available.

Data synthesis: Rotigotine has been investigated in early Parkinson's disease, as adjuvant therapy to levodopa in advanced Parkinson's disease, and in RLS. It is administered transdermally, which provides the convenience of once-daily dosing, constant drug delivery, and sustained stable plasma concentrations. In clinical trials of patients with early Parkinson's disease, rotigotine has decreased combined scores on the motor and activities of daily living sections of the Unified Parkinson's Disease Rating Scale up to 85 weeks. In patients with advanced Parkinson's disease, rotigotine reduced mean off-time when used as an adjuvant to levodopa. Rotigotine has decreased the severity of RLS in Phase III trials. Acute adverse events are similar to those of other dopamine agonists and are most common during the titration phase. Mild-to-moderate application site reactions are common.

Conclusions: Longer trials are required to determine whether transdermal rotigotine will reduce development of dyskinesias and motor fluctuations in Parkinson's disease and augmentation and rebound in RLS by preventing pulsatile dopamine stimulation associated with levodopa and other dopamine agonists.