The chronic treatment of Parkinson's disease with l-dopa is often associated with fluctuations of motor response and dyskinesias. Therefore, to overcome the adverse effects of the long-term use of l-dopa, directly acting dopamine receptor agonists have been introduced. However, l-dopa remains the most effective treatment of the slowness of movement, increased muscle tone, and tremor that are typical of Parkinson's disease. Why is this so? In this article, we discuss evidence that suggests that dopamine produced from l-dopa has a larger number of actions compared with dopamine receptor agonists. In addition to stimulating D1- and D2-like dopamine receptors, dopamine might also activate adrenoceptors, novel dopamine sites, the dopamine transporter and trace amine receptors, all of which might contribute to the superior effect of l-dopa in Parkinson's disease.
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