Challenges with Commonly Available Dopamine Agonists in Parkinson’s Disease

A panelist discusses how current FDA-approved dopamine agonists (DAs), which primarily target D2 and D3 receptors, present a complex clinical challenge due to the need to balance their efficacy with a notable risk of adverse events. While these medications are effective in alleviating motor symptoms and delaying the need for levodopa escalation, they are also associated with adverse effects such as impulse control disorders, hallucinations, psychosis, and excessive daytime sleepiness. These risks become especially concerning in vulnerable populations, such as older patients or those with cognitive impairment.

The panelist notes that many of these adverse effects are thought to stem from off-target activity on nondopaminergic receptor systems, particularly serotonergic and adrenergic pathways. This receptor cross-reactivity may inadvertently impact mood, behavior, and sleep-wake cycles, contributing to the development of adverse effects not directly related to dopamine signaling. The variability in patient responses underscores the importance of understanding each agent’s receptor binding profile and tailoring treatment based on individual risk factors.

In clinical practice, these adverse effects often limit the use of DAs, particularly in certain patient groups. For example, younger patients may tolerate them better and benefit from their levodopa-sparing effects, whereas older patients or those with psychiatric comorbidities may experience more harm than benefit. The panelist emphasizes that patient selection, close monitoring, and proactive communication about possible adverse effects are key to safely incorporating dopamine agonists into Parkinson disease management strategies.