One of the main goals of current research on new therapies for Parkinson’s disease is to identify alternatives to the conventional stimulation of the dopaminergic system with L-DOPA or dopamine agonists. Although these treatments remain the cornerstone of symptom management, their long-term use is often associated with significant side effects, such as motor fluctuations and dyskinesias. This has led scientists to search for novel strategies that can both relieve symptoms and potentially slow the progression of the disease.

Among the promising approaches under investigation is the targeting of the metabotropic glutamate receptor subtype 4 (mGluR4). This receptor plays an important role in modulating basal ganglia circuits that are disrupted in Parkinson’s disease. Recent studies from several academic groups have shown that positive allosteric modulators (PAMs) of mGluR4 represent a particularly attractive therapeutic option. By enhancing the activity of this receptor, mGluR4 PAMs may not only improve motor function but could also provide disease-modifying effects. In fact, preliminary findings suggest that these compounds might be capable of halting, or at least significantly slowing, the progression of neurodegeneration in Parkinson’s disease.