Potential of transdermal drug delivery in Parkinson's disease

There has been a growing recognition that pulsatile stimulation of dopamine receptors may be an important mechanism in the generation of the motor fluctuations that often develop and compromise the effectiveness of long-term levodopa administration in persons with Parkinson's disease (PD). This has prompted investigation of treatment approaches that might provide more constant, and therefore physiological, dopamine receptor stimulation. Frequent levodopa administration, controlled-release levodopa preparations, inhibitors of levodopa metabolism, and duodenal, subcutaneous and even intravenous infusions of levodopa or dopamine agonists have all been employed with this goal in mind, but all have limitations. Transdermal drug delivery is a treatment approach that is not only capable of providing a constant rate of drug delivery, but is also non-invasive and relatively simple to use. However, developing a drug to be delivered transdermally for the treatment of PD has been anything but easy. Levodopa and many dopamine agonists are not sufficiently soluble to be administered via the transdermal route, and blind alleys have been encountered thus far in the investigation of suitably soluble drugs. Nevertheless, investigation continues and yet another candidate drug, rotigotine (N-0923), is currently under active investigation. Techniques designed to enhance skin permeation and thus improve the effectiveness of transdermal drug delivery are also potential sources for future treatment advances.