Important modifications further enhanced efficacy, such as the co-administration of levodopa with a decarboxylase inhibitor. Levodopa has not been without important side effects and limitations in its long-term use. There is a shortening of the beneficial response to L-dopa. Other studies have shown that the decreased benefit of levodopa with time may be related to changes in the receptors for dopamine on the striatal cells and perhaps to changes in the connections from the striatum to the subthalamic nucleus and the globus pallidum.
Dyskinesias are another problem that develop during long-term levodopa use.
There is evidence that dyskinesias can appear after a single dose of levodopa in some PD patients. The mechanism underlying this is not well understood. Dyskinesias are troublesome and frequently limit the ability to treat PD effectively. Patients with uncontrolled, violent dyskinesias are often candidates for pallidotomy or deep brain stimulation. And to date, there is no convincing evidence that chronic administration of levodopa causes any adverse effects on dopamine cells in normal humans or on the viability of the remaining dopamine cells in PD patients.