Lurasidone (SM-13496) is an antagonist of dopamine D ₂ and 5-HT ₇ with IC ₅₀ s of 1.68±0.09 and 0.495±0.090 nM, respectively. Lurasidone (SM-13496) is also a partial agonist of 5-HT _1A receptor with an IC ₅₀ of 6.75±0.97 nM. In vitro receptor binding experiments reveal that Lurasidone (SM-13496) demonstrates affinity for dopamine D ₂ and 5-HT _2A receptors higher than other tested antipsychotics. Lurasidone (SM-13496) does not increase [ ³⁵ S]GTPγS binding to the membrane preparations for dopamine D ₂ receptors by itself, but it antagonizes dopamine-stimulated [ ³⁵ S]GTPγS binding in a concentration-dependent manner with a K _B value of 2.8±1.1 nM.

Lurasidone (SM-13496) dose-dependently increases the ratio of DOPAC/dopamine in frontal cortex and striatum, but it shows a preferential effect on the frontal cortex compare with the striatum, especially at higher doses. Lurasidone (SM-13496) (ED ₅₀ values 2.3 to 5.0 mg/kg) shows a comparable potency with olanzapine (ED ₅₀ values 1.1 to 5.1 mg/kg), higher potency than clozapine (ED ₅₀ 9.5 to 290 mg/kg), and slightly lower potency than haloperidol (ED ₅₀ values 0.44 to 1.7 mg/kg). Lurasidone (SM-13496) (1 to 10 mg/kg) dose-dependently inhibits conditioned avoidance response (CAR) in rats, and the ED ₅₀ values are 6.3 mg/kg. Lurasidone (SM-13496) dose-dependently inhibits tryptamine (TRY)-induced forepaw clonic seizure and p-chloroamphetamine (p-CAMP)-induced hyperthermia with ED ₅₀ values of 5.6 and 3.0 mg/kg, respectively. Lurasidone (SM-13496) (0.3 to 30 mg/kg) dose-dependently and significantly increases the number of shocks received by rats in the conflict test with MED of 10 mg/kg (p<0.01).