Lurasidone

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Lurasidone 是多巴胺 D2 和 5-HT7 的拮抗剂（IC50 分别为 1.68 和 0.495 nM）。它也是 5-HT1A 受体的部分激动剂（IC50 ： 6.75 nM）。

Lurasidone is an antagonist of both dopamine D2 and 5-HT7(IC50=1.68 and 0.495 nM, respectively).It also a partial agonist of 5-HT1A receptor(IC50 : 6.75 nM).In addition to its principal antagonist activity at dopamine D2 and serotonin 5-HT2A receptors, lurasidone has distinctive 5-HT7 antagonistic activity, and displays partial agonism at 5-HT1A receptors, as well as modest antagonism at noradrenergic α2A and α2C receptors.?Lurasidone is devoid of antihistaminic and anticholinergic activities.Lurasidone is administered once daily within the range of 40-160 mg/day for schizophrenia and 20-120 mg/day for bipolar depression, and its pharmacokinetic profile requires administration with food.?In adult healthy subjects and patients, a 40 mg dose results in peak plasma concentrations in 1-3 h, a mean elimination half-life of 18 h (mostly eliminated in the feces), and apparent volume of distribution of 6173 L;?it is approximately 99 % bound to serum plasma proteins.?Lurasidone's pharmacokinetics are approximately dose proportional in healthy adults and clinical populations within the approved dosing range, and this was also found in a clinical study of children and adolescents.?Lurasidone is principally metabolized by cytochrome P450 (CYP) 3A4 with minor metabolites and should not be coadministered with strong CYP3A4 inducers or inhibitors.?Lurasidone does not significantly inhibit or induce CYP450 hepatic enzymes.

Lurasidone (SM-13496) is an antagonist of dopamine D2 and 5-HT7 with IC50s of 1.68±0.09 and 0.495±0.090 nM, respectively. Lurasidone (SM-13496) 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 (SM-13496) demonstrates affinity for dopamine D2 and 5-HT2A receptors higher than other tested antipsychotics. Lurasidone (SM-13496) 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.

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) (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 (SM-13496) (1 to 10 mg/kg) dose-dependently inhibits conditioned avoidance response (CAR) in rats, and the ED50 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 ED50 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).

SM-13496

Endocrinology/Hormones

5-HT Receptor

5-HT7|5-HT1A|D2

nervous system

Bipolar Depression

367514-87-2

492.68

C28H36N4O2S

>98% (HPLC)

DMSO:17.83 mg/mL (36.19mM; Need ultrasonic)

[H][C@@]12[C@H]3CC[C@H](C3)[C@]1([H])C(=O)N(C[C@@H]1CCCC[C@H]1CN1CCN(CC1)c1nsc3ccccc13)C2=O

——

(-20℃)

With Ice Pack

≥ 2 years