鲁拉西酮
中文名称:
鲁拉西酮
中文同义词:
鲁拉西酮;鲁拉西酮(仅供中间体);盐酸鲁拉西酮API;卢拉西酮;鲁拉西酮LURASIDONE;鲁拉西;盐酸鲁拉西酮/鲁拉西酮
英文名称:
lurasidone
英文同义词:
4-{[(1R,2R)-2-{[4-(2$l^{4}-thia-6-azatricyclo[5.4.0.0^{2,6}]undeca-1(11),2,4,7,9-pentaen-5-yl)piperazin-1-yl]Methyl}cyclohexyl]Methyl}-4-azatricyclo[5.2.1.0^{2,6}]deca-1(9),2(6),7-triene-3,5-dione;lurasidone;(3aR,4S,7R,7aS)-2-[[(1R,2R)-2-[[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl]methyl]cyclohexyl]methyl]hexahydro-4,7-methano-1H-isoindole-1,3(2H)-dione;Lurasidone (SM13496);(3aR,4S,7R,7aS)-2-{[(1R,2R)-2-{[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]Methyl}cyclohexyl]Methyl}hexahydro-1H-4,7-Methanoisoindole-1,3(2H)-dione;urasidone;Lurasidone, >=98%;Lurasidone Base
CAS号:
367514-87-2
分子式:
C28H36N4O2S
分子量:
492.68
EINECS号:
696-042-8
相关类别:
医药中间体;原料药;神经系统药物;药物杂质及中间体;兽药原料;化工原料;医药原料药;Pharmaceutical intermediate
Mol文件:
367514-87-2.mol
沸点
623.4±55.0 °C(Predicted)
密度
1.273
酸度系数(pKa)
8.41±0.50(Predicted)
CAS 数据库
367514-87-2
治疗精神分裂症药物
鲁拉西酮是由日本Dainippon Sumitomo制药公司开发一种非典型抗精神病药物，属化药注册分类3.1类，适用于精神分裂症患者的治疗。在四项6周成年精神分裂患者对照研究中确定疗效。其治疗精神分裂症的确切机制像其他非典型抗精神病药一样仍未十分清楚，可能与多巴胺D2 和5-羟色胺2A（5-HT2A）受体的拮抗作用有关。其用于精神分裂症的治疗，有研究报道鲁拉西酮可以改善认知功能。
2010年10月28日美国FDA批准盐酸鲁拉西酮（lurasidone HCI）每日一次片剂用于精神分裂症患者一线治疗，其商品名为Latuda。
用法与用量：推荐起始剂量为40 mg·d，有效剂量范围为40～120 mg·d，最大推荐剂量为80 mg·d。应与食物同时服用。
不良反应：常见的不良反应有嗜睡、静坐不能、恶心、帕金森病症样症状和情绪激动焦虑。鲁拉西酮无身体依赖性，较少引起体重增加，不引起葡萄糖、脂质（类脂）、ECG和QT间期改变。
生物活性
Lurasidone (SM-13496) 是 dopamine D2 和 5-HT7 的拮抗剂，IC50 值分别为 1.68 和 0.495 nM。 Lurasidone (SM-13496) 也是 5-HT1A 受体的部分激动剂，IC50 值为 6.75 nM。
靶点
Target Value
5-HT2A
(Cell-free assay) 0.5 nM(Ki)
5-HT7 receptor
(Cell-free assay) 0.5 nM(Ki)
D2 receptor
(Cell-free assay) 1 nM(Ki)
5-HT1A receptor
(Cell-free assay) 6.4 nM(Ki)
Target
Value
5-HT2A
(Cell-free assay)
0.5 nM(Ki)
5-HT7 receptor
(Cell-free assay)
0.5 nM(Ki)
D2 receptor
(Cell-free assay)
1 nM(Ki)
5-HT1A receptor
(Cell-free assay)
6.4 nM(Ki)
体外研究
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.
体内研究
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).
