Mechanism of action and pharmacology

The antipsychotic activity of CAPLYTA is thought to be mediated through a combination of antagonism of serotonin 5-HT_2A receptors and postsynaptic antagonism of dopamine D₂ receptors. The mechanism of action of CAPLYTA is unknown.¹

CAPLYTA simultaneously has:

Affinity at 5-HT_2A approximately 60 times higher than at dopamine D₂^1,2*

High 5-HT_2A/D₂ occupancy ratio allows for lower amounts of dopamine D₂ antagonism at therapeutic doses³

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

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

Elevated levels of dopamine D₂ receptor occupancy are known to be associated with increases in extrapyramidal symptoms (EPS) and prolactin³

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

*5-HT_2A (K_i=0.48 nM); D₂ (K_i=47 nM); human recombinant receptor expressed in HEK-293 cells. Observed values may vary.²

CAPLYTA receptor-binding profile^1,2

High binding affinity for 5-HT_2A and moderate binding affinity for dopamine D₂¹
Low affinity for off-target receptors^1,3 - CAPLYTA shows little affinity (<50% inhibition at 100 nM) at muscarinic and histaminergic receptors

CAPLYTA® (lumateperone) has a high binding affinity for 5-HT2A, moderate binding affinity for dopamine D2, and low affinity for off-target receptors.

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Resources

References: 1. CAPLYTA prescribing information. 2. Data on File. 2021. 3. Davis RE, Correll CU. ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes. Expert Rev Neurother. 2016(6):601-614. 4. Kumar B, Kuhad A, Kuhad A. Lumateperone: a new treatment approach for neuropsychiatric disorders. Drugs Today (Barc). 2018;54(12):713-719.

Mechanism of action and pharmacology

CAPLYTA simultaneously has:

Affinity at 5-HT2A approximately 60 times higher than at dopamine D21,2*

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

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

Elevated levels of dopamine D2 receptor occupancy are known to be associated with increases in extrapyramidal symptoms (EPS) and prolactin3

CAPLYTA receptor-binding profile1,2

Affinity at 5-HT_2A approximately 60 times higher than at dopamine D₂^1,2*

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

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

Elevated levels of dopamine D₂ receptor occupancy are known to be associated with increases in extrapyramidal symptoms (EPS) and prolactin³

CAPLYTA receptor-binding profile^1,2