Review: Therapeutic options for continuous dopaminergic stimulation in Parkinson's disease

Abstract

Treatment of Parkinson's disease aims to replace dopaminergic transmission at striatal synapses. In the normal state, nigral neurons fire continuously, exposing striatal dopamine receptors to relatively constant levels of dopamine. In the disease state, periodic dosing and the short half-life of antiparkinsonian drugs leads to more intermittent stimulation. Abnormal pulsatile stimulation of striatal dopamine receptors may lead to dysregulation of genes and proteins in downstream neurons and consequently, alterations in neuronal firing patterns. This may ultimately lead to motor complications. In order to prevent the development of motor complications a therapy that provides continuous dopaminergic stimulation as observed in the normal state would be ideal. Different routes of administration of levodopa and other dopaminergic drugs have been tried to achieve continuous dopaminergic stimulation (CDS). This review discusses the various methods available to achieve this goal with particular emphasis on duodenal dopa administration.