In a part of the brain called the basal ganglia, balanced signaling between two neuronal pathways maintain normal movement. These are known as the indirect pathway and the direct pathway. In Parkinson’s disease, the indirect pathway is overactive, which leads to a decrease in motor activity.
AP-472 is a Positive Allosteric Modulator (a “PAM”) of the metabotropic glutamate receptor subtype 4, or “mGlu4”. This means it helps activate mGlu4 signaling. This activation results in a decrease neuronal transmission through the indirect pathway, which helps restore the Parkinson’s patient’s ability to move.
AP-612 is a Negative Allosteric Modulator (a “NAM”) of the metabotropic glutamate receptor subtype 5, or “mGlu5”. This means it helps decrease mGlu5 signaling. A wealth of preclinical and clinical data suggest that inhibiting mGlu5 activity could be useful in treating multiple CNS disorders, particularly those relating to pain and depression/anxiety.