Lurasidone hydrochloride

Lurasidone is an atypical antipsychotic developed by Dainippon Sumitomo Pharma. It was approved by the U.S. Food and Drug Administration (FDA) for treatment of schizophrenia on October 29, 2010 and is currently pending approval for the treatment of bipolar disorder in the United States. (In Vitro) :Lurasidone (Hydrochloride) (SM-13496 (Hydrochloride) ) is an antagonist of dopamine D2 and 5-HT7 with IC50s of 1.68±0.09 and 0.495±0.090 nM, respectively. Lurasidone (Hydrochloride) (SM-13496 (Hydrochloride) ) is also a partial agonist of 5-HT1A receptor with an IC50 of 6.75±0.97 nM. In vitro receptor binding experiments reveal that Lurasidone (Hydrochloride) (SM-13496 (Hydrochloride) ) demonstrates affinity for dopamine D2 and 5-HT2A 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 KB value of 2.8±1.1 nM. (In Vivo) :Lurasidone (Hydrochloride) (SM-13496 (Hydrochloride) ) 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 (Hydrochloride) (SM-13496 (Hydrochloride) ) (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 (Hydrochloride) (SM-13496 (Hydrochloride) ) (1 to 10 mg/kg) dose-dependently inhibits conditioned avoidance response (CAR) in rats, and the ED50 values are 6.3 mg/kg. Lurasidone (Hydrochloride) (SM-13496 (Hydrochloride) ) 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 (Hydrochloride) (SM-13496 (Hydrochloride) ) (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) .