Mechanism of action and pharmacology

CAPLYTA activity may involve antagonism at 5‑HT_2A and partial agonism at D₂ receptors¹

The mechanism of action of CAPLYTA is unknown. The activity of CAPLYTA is thought to be mediated through a combination of antagonism of central serotonin 5‑HT_2A receptors and partial agonism at central dopamine D₂ receptors.¹

Receptor binding of CAPLYTA

High Affinity¹

5-HT_2A

K_i = 0.5

Nearly full saturation for serotonin 5-HT_2A

Full saturation: >80% occupancy¹

Allows for lower amounts of D₂ receptor occupancy at therapeutic doses²

Moderate Affinity¹

D₂

K_i = 32

39% receptor occupancy¹

High D₂ receptor occupancy is linked to increased risks of EPS and elevated prolactin levels²

Moderate Affinity¹

SERT

K_i = 33

Inhibition of SERT contributes to increased serotonin in the synapse²

D₁

K_i = 41

May contribute to indirect activation of the glutamatergic AMPA and NMDA receptors³

Low Affinity¹

OFF-TARGET RECEPTORS

(e.g., muscarinic and histaminergic receptors)

α_1A,1B

K_i < 100

H_1, M_1-5

K_i > 1000*

Binding affinity shown above by K_i values. Affinity is at the therapeutic dose.

*CAPLYTA shows little affinity (<50% inhibition at 100 nM) at muscarinic and histaminergic receptors.¹

EPS=extrapyramidal symptoms.