Smoothing out the Ups and Downs

The progressive loss of nigrostriatal dopaminergic neurons with advancing disease exposes the trough between every dose of levodopa in Parkinson’s disease. This is due to the combination of a loss of native dopamine production to fill in this interdose interval and a reduction in dopaminergic terminals to take up and release dopamine long beyond its short plasma half-life. The clinical result is wearing off—an awareness in patients of returning symptomatology while waiting for their next dose. Where consistent and impacting negatively on function on any level, there are a number of initial oral approaches to smooth out dopaminergic stimulation before more invasive advanced therapeutic options need to be considered.