Dopamine receptor agonists for the treatment of early or advanced Parkinson's disease

Dopamine receptor agonists are indicated for the treatment of motor symptoms at all stages of Parkinson’s disease, including those patients with advanced Parkinson’s, and the amerlioration of levodopa-related motor fluctuations. The development of ergolinic agonists, including bromocriptine and pergolide, was followed by the appearance of non-ergolinic agents, such as pramipexole and ropinirole, that had the added advantage of reducing the risk of fibrotic reactions. Daily, controlled-release oral and transdermal formulations have been developed in order to provide a stable plasma drug concentration over 24 hours, but a disease-modifying effect has yet to be clinically demonstrated. Dopamine agonists are also associated with significant adverse effects, perhaps related to dopaminergic hyperactivation, that were identified in pre-marketing clinical trials and include nausea, hallucinations, confusion and orthostatic hypotension. During post-marketing surveillance, further identified adverse effects have included daytime somnolence, impulse-control disorders and heart valve fibrosis. Other issues, including the efficacy of dopamine agonists for the treatment of non-motor symptoms, remain under evaluation.