SUMMARY

• Lumateperone has high binding affinity for serotonin 5-HT_2A receptors (K_i=0.54 nM) and moderate binding affinity for dopamine D₂ (K_i=32 nM) receptors.¹
• Vanover et al (2019)² conducted an open-label (OL) positron emission tomography (PET) study to evaluate dopamine D₂ receptor occupancy (D₂RO) at plasma steady state following 2 weeks of treatment with 42 mg of CAPLYTA daily in the morning in patients with schizophrenia (N=10).
  • Following administration of a CAPLYTA dose of 42 mg, the highest D₂RO level in the dorsal striatum was observed 1 hour after dosing, with a mean±standard deviation (SD) occupancy of 39%±12% (n=6).

PRODUCT LABELING

Mechanism of Action

The mechanism of action of lumateperone for the treatment of schizophrenia in adults, for the treatment of depressive episodes associated with bipolar depression (as monotherapy or as adjunctive therapy with lithium or valproate), and as adjunctive therapy with antidepressants for the treatment of MDD is unknown. However, the mechanism of action of lumateperone for these uses could be mediated through a combination of antagonist activity at central serotonin 5-HT_2A receptors and partial agonist activity at central dopamine D₂ receptors.¹

Pharmacodynamics

Lumateperone has high binding affinity for serotonin 5-HT_2A receptors (K_i=0.54 nM) and moderate binding affinity for dopamine D₂ (K_i=32 nM) receptors.¹

CLINICAL DATA

Vanover et al (2019)² conducted an OL, PET study to evaluate the D₂RO at plasma steady state following 2 weeks of treatment with 42 mg of CAPLYTA daily in the morning in patients with schizophrenia (N=10; mean age, 39.3 years). All enrolled patients discontinued their previous antipsychotic medication to establish a drug-free baseline using a 2-week washout period. During the study, 9 patients received lorazepam as a concomitant psychotropic medication.

D₂RO Following CAPLYTA Treatment

• Following administration of a CAPLYTA dose of 42 mg, the highest D₂RO level in the dorsal striatum was observed at 1 hour, with a mean±SD occupancy of 39%±12% (n=6).
• The mean±SD dorsal striatal D₂RO gradually decreased from 34%±8% at 3 to 4 hours after dosing to 19%±10% at 7.5 hours after dosing, and 7%±7% at 24 to 27 hours after dosing (n=4).
• Combined data from all patients at 1 or 3 hours revealed a mean D₂RO of 37%, with an associated mean total plasma level of 49.3 ng/mL. A statistically significant correlation was observed between D₂RO and total plasma concentration (r²=0.6; P=0.0077).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 07 October 2025.