Lurasidone HCl

产品描述

Lurasidone是非典型的抗精神病药物，抑制Dopamine D2,5-HT2A,5-HT7, 5-HT1A和去甲肾上腺素α2C，IC50分别为1.68 nM, 2.03 nM, 0.495 nM, 6.75 nM和10.8 nM。

靶点

Dopamine D2

5-HT2A

5-HT7

5-HT1A

noradrenaline α2C

IC50

1.68 nM

2.03 nM

0.495 nM

6.75 nM

10.8 nM

体外研究

Lurasidone antagonizes dopamine-stimulated [35S]GTPγS binding at human dopamine D2L receptor in a concentration-dependent manner with a KB value of 2.8 nM. Lurasidone antagonizes 5-HT-stimulated cAMP accumulation in the CHO/h5-HT7 cells with a KB value of 2.6 nM. Lurasidone partially stimulates [35S]GTPγS binding to the membrane preparation for human 5-HT1A receptors with a maximum effect of 33%. Lurasidone dose-dependently increases the ratio of DOPAC/dopamine in rat frontal cortex and striatum.

体内研究

The inhibitory actions of Lurasidone on MAP-induced hyperactivity persists for more than 8 hours, and the ED50 values of the action at 1 hour, 2 hours, 4 hours, and 8 hours after the treatment are 2.3 mg/kg, 0.87 mg/kg, 1.6 mg/kg, and 5.0 mg/kg, respectively. Lurasidone (1 mg/kg–10 mg/kg) dose-dependently inhibits conditioned avoidance response in rats with ED50 of 6.3 mg/kg. Lurasidone dose-dependently inhibits TRY-induced forepaw clonic seizure and p-CAMP-induced hyperthermia in rats with ED50 of 5.6 mg/kg and 3.0 mg/kg, respectively. Lurasidone (0.3 mg/kg–30 mg/kg) dose-dependently and significantly increases the number of shocks received by rats in the Vogel’s conflict test with MED of 10 mg/kg. Lurasidone (3 mg/kg, 2 weeks) significantly suppresses hyperactivity behavior in olfactory bulbectomy model rats. Lurasidone (700 mg/kg–1000 mg/kg) slightly prolongs the duration of loss of righting reflexes elicited by hexobarbital (anesthesia) in mice in a dose-dependent manner.Lurasidone (30 mg/kg, p.o.) significantly and dose-dependently reverses the MK-801-induced impairment of the passive-avoidance response of rats.Lurasidone (3 mg/kg p.o.) potently reverses MK-801-induced learning impairment in the Morris water maze test in rats. Lurasidone (3 mg/kg p.o.) potently reverses MK-801-induced reference memory impairment and moderately but not significantly attenuates MK-801-induced working memory impairment in the radial-arm maze test.Lurasidone (10 mg/kg) treatment increases total BDNF mRNA levels in rat prefrontal cortex and, to less extent, in hippocampus. Lurasidone (10 mg/kg) significantly increases the levels of mature BDNF protein in rat prefrontal cortex, without affect the protein levels of the neurotrophin (both precursor and mature forms) in hippocampal extracts.

溶解性

DMSO 1 mg/mL，水<1 mg/mL，乙醇<1 mg/mL

稳定性

2年-20°C粉状，6月-80°C溶于DMSO

特征