Biochem/physiol Actions

Lumateperone tosylate (ITI-007) is an orally active, potent 5-HT2A antagonist, postsynaptic D2 antagonist, and serotonin transporter SERT inhibitor (K_i = 0.5, 32, 62 nM, respectively) with in vivo antipsychotic efficacy and no effect toward receptors associated with cognitive and metabolic side effects of antipsychotic drugs (e.g., H1, 5-HT2C, muscarinic). ITI-007 blocks DOI-induced headtwitch (ID₅₀ = 0.09 mg/kg, po.) and D-AMPH-induced hyperlocomotion in mice (ID₅₀ = 0.95 mg/kg, po.), while also acting as a partial agonist at presynaptic striatal D2 receptors.