Pharmacology of CAPLYTA

The antipsychotic activity of CAPLYTA is thought to be mediated through a combination of antagonism of serotonin 5-HT2A receptors and postsynaptic antagonism of dopamine D2 receptors1

CAPLYTA simultaneously has:

Affinity at 5-HT2A approximately 60x HIGHER than at dopamine D21,3*

High 5-HT2A/D2 occupancy ratio allows for lower amounts of dopamine D2 antagonism at therapeutic doses7

A moderate binding affinity for dopamine D2, D1, and SERT1

A low binding affinity for off‑target receptors like muscarinic and histaminergic receptors1

The binding of CAPLYTA to the D₁ receptor may contribute to indirect activation of the AMPA and NMDA receptors

The binding of CAPLYTA to the D1 receptor may contribute to indirect activation of the AMPA and NMDA receptors8

The mechanism of action of CAPLYTA is unknown.

Elevated levels of dopamine D2 receptor occupancy are known to be associated with increases in EPS and prolactin.7

5-HT2A (ki=0.48 nM); D2 (ki=47 nM); human recombinant receptor expressed in HEK-293 cells. Observed values may vary.3

CAPLYTA receptor-binding profile1,2,7

CAPLYTA® (lumateperone) receptor-binding profile
  • High binding affinity for 5-HT2A and moderate binding affinity for dopamine D21
  • Low affinity for off-target receptors1
    • CAPLYTA shows little affinity (<50% inhibition at 100 nM) at muscarinic and histaminergic receptors1

Frequently asked questions about pharmacology

References: 1. CAPLYTA full prescribing information. 2. Bantick RA, Deakin JF, Grasby PM. The 5-HT1A receptor in schizophrenia: a promising target for novel atypical neuroleptics? J Psychopharmacol. 2001;15(1):37-46. 3. Vanover KE, O'Gorman C, Correll CU, et al. Lumateperone (ITI-007): a novel investigational agent with broad therapeutic potential across multiple neuropsychiatric disorders. Eur Neuropsychopharmacol. 2017;27:S660-S661.