tcsc0866 Lurasidone (Hydrochloride)

Lurasidone is an antagonist of both dopamine D₂ and 5-HT₇ with IC₅₀s of 1.68 and 0.495 nM, respectively. Lurasidone is also a partial agonist of 5-HT_1A receptor with an IC₅₀ of 6.75 nM.

IC50 & Target: IC50: 1.68 nM (dopamine D₂), 0.495 nM (5-HT₇), 6.75 nM (5-HT_1A)^[1]

In Vitro: Lurasidone is an antagonist of dopamine D₂ and 5-HT₇ with IC₅₀s of 1.68±0.09 and 0.495±0.090 nM, respectively. Lurasidone is also a partial agonist of 5-HT_1A receptor with an IC₅₀ of 6.75±0.97 nM. In vitro receptor binding experiments reveal that Lurasidone demonstrates affinity for dopamine D₂ and 5-HT_2A receptors higher than other tested antipsychotics. Lurasidone does not increase [³⁵S]GTPγS binding to the membrane preparations for dopamine D₂ receptors by itself, but it antagonizes dopamine-stimulated [³⁵S]GTPγS binding in a concentration-dependent manner with a K_B value of 2.8±1.1 nM^[1].

In Vivo: Lurasidone dose-dependently increases the ratio of DOPAC/dopamine in both regions, but it shows a preferential effect on the frontal cortex compare with the striatum, especially at higher doses. Lurasidone (ED₅₀ values 2.3 to 5.0 mg/kg) shows a comparable potency with olanzapine (ED₅₀ values 1.1 to 5.1 mg/kg), higher potency than clozapine (ED₅₀ 9.5 to 290 mg/kg), and slightly lower potency than haloperidol (ED₅₀ values 0.44 to 1.7 mg/kg). Lurasidone (1 to 10 mg/kg) dose-dependently inhibits conditioned avoidance response (CAR) in rats, and the ED₅₀ values are 6.3 mg/kg. Lurasidone dose-dependently inhibits TRY-induced forepaw clonic seizure and p-CAMP-induced hyperthermia with ED₅₀ values of 5.6 and 3.0 mg/kg, respectively. Lurasidone (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)^[1].