Pharmacology
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 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
- 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
The generic name of CAPLYTA is lumateperone.1
CAPLYTA belongs to a class of drugs known as atypical antipsychotics.1,2
The clearance of CAPLYTA is about 27.9 L/hour and the terminal half-life of CAPLYTA is about 18 hours after administration.1 Following a once-daily oral administration of CAPLYTA, lumateperone steady state is reached in about 5 days.1
CAPLYTA exhibits moderate affinity for the dopamine D1 receptor.1 The binding of CAPLYTA to the dopamine D1 receptor may contribute to indirect activation of the glutamatergic AMPA and NMDA receptors.3 The clinical relevance of CAPLYTA receptor-binding affinities is unknown.1
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.