Lumateperone

There is much to learn about the pathophysiology of schizophrenia; however, dopamine abnormalities, specifically in the prefrontal and mesolimbic brain regions, are consistent in people with schizophrenia. In addition to dopamine, other neurotransmitters such as serotonin, glutamate, GABA and acetylcholine are thought to play a role.

Lumateperone is unique among second generation antipsychotics based on its target profile and dopamine D2 receptor occupancy. Unlike other antipsychotics, lumateperone has partial agonist activity at presynaptic dopamine (D2) receptors, resulting in reduced presynaptic release of dopamine, and antagonistic activity at postsynaptic dopamine (D2) receptors. These characteristics allow lumateperone to efficiently reduce dopamine signaling.

Lumateperone also targets dopamine (D1) receptors, and a useful secondary result of D1 activation is increased glutamatergic N-methyl-D-aspartate (NMDA) GluN2B receptor phosphorylation. This is significant since NMDA mediated glutamate signaling appears to be impaired in patients who have schizophrenia.

Finally, lumateperone is capable of modulating serotonin by inhibiting serotonin transporters (SERT), and by behaving as a 5-HT2A receptor antagonist.