|Other names||ITI-007; ITI-722|
|Chemical and physical data|
|Molar mass||393.506 g·mol−1|
|3D model (JSmol)|
Lumateperone (INN; brand name Caplyta kəp-LY-tə, developmental codes ITI-007 and ITI-722) is a butyrophenone atypical antipsychotic developed by Intra-Cellular Therapies, licensed from Bristol-Myers Squibb, for the treatment of schizophrenia, and currently in development for bipolar depression and other neurological indications.
Two phase III lumateperone monotherapy studies were conducted and completed for the treatment of bipolar depression, those being trial Study 401 and Study 404. A third trial, Study 402, aims to test lumateperone in addition to lithium or valproate, the data pertaining this trial is due out in 2020.
Study 401 was conducted solely in the United States while Study 404 was a global study and included patients from the US. Of the entire Study 404 population (381 patients), two-thirds were from Russia and Colombia. At the completion of the two monotherpay phase III trials only Study 404 met its primary endpoint and one of its secondary endpoints. In Study 404, patients received 42 mg lumateperone once daily or placebo for six weeks. Study 404 patients saw an improvement of depressive symptoms compared to placebo as documented by a change in MADRS total score of 4.6.
Lumateperone affects multiple systems (serotonergic, dopaminergic and glutamatergic) in the central nervous system. It acts as a antagonist of 5-HT2A 0.54nM receptor and modulates D1 4.1nM and D2 3.2nM dopamine receptors where it is a partial agonist at presynaptic and antagonist at postsynaptic receptors. Serotonin transporters at 3.3nM. Through the mTOR pathway, lumateperone augments both NMDA and AMPA activity. Because of its complex pharmacology, it is not clear which of these activities are primarily responsible for its antidepressive and antipsychotic activities.
Lumateperone has a Tmax of 3–4 hours and a half-life of 13 hours. The main metabolite is the reduction of the carbonyl to hydroxyl group by a ketone reductase. The N-methyl group is also dealkylated by CYP3A4.