Schizophrenia

VU10010 acts as an allosteric potentiator of the M4 mACh receptor. VU10010 induces a 50-fold leftward shift of the ACh concentration response curve. VU10010 has an EC₅₀ near 100 nM for the M4 receptor subtype but no activity at any other subtype even at concentrations as high as 100 μM. VU10010 has no detectable affinity for the ACh binding site but allosterically increases affinity of the M4 subtype for ACh. This remarkable specificity, along with the concomitant advantages of allosteric modulation (see Figure 3A), may conform to the ligand characteristics necessary to target pathways and symptoms of complex diseases such as schizophrenia. See text for details.