L-365260

L-365260用途

L-365260是一种有效和选择性的非肽胃泌素和脑胆囊收缩素受体(CCK-B)拮抗剂,Kis分别为1.9nM和2.0nM。L-365260以立体选择性和竞争性方式与豚鼠胃胃泌素和脑CCK受体相互作用。L-365260可增强吗啡镇痛,防止吗啡耐受[1][2][3]。

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L-365260名称

[ CAS 号 ]:
118101-09-0

[ 中文名 ]:
L-365,260,CCK2拮抗剂

[ 英文名 ]:
L-365,260

[英文别名 ]:

L-365260

L-365260生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 胆囊收缩素受体

研究领域 >> 代谢疾病

研究领域 >> 神经疾病

[ 靶点 ]

Ki: 1.9 nM (gastrin); 2.0 nM (CCK-B)[1]

[体外研究]

L-365260(1μM)强烈减弱不同神经元中CCK8S和CCK4介导的去极化作用[2]。L-365260对大鼠、小鼠和人的脑CCK-B受体具有类似的高亲和力,而对狗组织中的胃泌素和脑CCK-B(IC50=20-40 nM)受体具有较低的亲和力[1]。

[体内研究]

L-365260(0.01-10 mg/kg；s、 c.)增强亚最大剂量吗啡(4 mg/kg)诱导的大鼠镇痛作用[3]。L-365260(0.2 mg/kg；s、 c.每天两次,持续5天)显著延长大鼠吗啡镇痛的持续时间[3]。L-365260(0.1-30 mg/kg；p、 o.)拮抗小鼠(ED50=0.03 mg/kg)、大鼠(ED50=0.9 mg/kg)和豚鼠(ED50=5.1 mg/kg)胃泌素刺激的酸分泌[1]。动物模型：雄性Sprague-Dawley大鼠(300-350 g)注射吗啡[3]剂量：0.01,0.05,0.1,0.2,0.75,1.0,10.0 mg/kg给药：在腹腔注射4 mg/kg吗啡前10分钟皮下注射。结果：吗啡镇痛增强。

[参考文献]

[1]. Lotti VJ, et, al. A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK-B) ligand: L-365,260. Eur J Pharmacol. 1989 Mar 21;162(2):273-80.

[2]. Chung L, et, al. Cholecystokinin action on layer 6b neurons in somatosensory cortex. Brain Res. 2009 Jul 28;1282:10-9.

[3]. Dourish CT, et, al. The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. Eur J Pharmacol. 1990 Jan 25;176(1):35-44.

L-365260物理化学性质

[ 密度 ]:
1.23g/cm3

[ 沸点 ]:
611.5ºC at 760 mmHg

[ 分子式 ]:
C₂₄H₂₂N₄O₂

[ 分子量 ]:
398.45700

[ 闪点 ]:
323.6ºC

[ 精确质量 ]:
398.17400

[ PSA ]:
73.80000

[ LogP ]:
3.92110

[ 蒸汽压 ]:
6.85E-15mmHg at 25°C

[ 折射率 ]:
1.648

[ 储存条件 ]:
2-8°C

L-365260MSDS

详细MSDS(安全技术说明书)

L-365260安全信息

[ 符号 ]:

GHS06, GHS09

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H400

[ 警示性声明 ]:
P273-P301 + P310

[ 危险品运输编码 ]:
UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all

L-365260文献

Combination pharmacotherapy for the treatment of neuropathic pain in adults.

Cochrane Database Syst. Rev. 7 , CD008943, (2012)

Pharmacotherapy remains an important modality for the treatment of neuropathic pain. However, as monotherapy current drugs are associated with limited efficacy and dose-related side effects. Combining...

Modeled structure of a G-protein-coupled receptor: the cholecystokinin-1 receptor.

J. Med. Chem. 48(1) , 180-91, (2005)

The Cholecystokinin-1 receptor (CCK1R) mediates actions of CCK in areas of the central nervous system and of the gut. It is a potential target to treat a number of diseases. As for all G-protein-coupl...

A cholecystokinin-1 receptor agonist (CCK-8) mediates increased permeability of brain barriers to leptin.

Br. J. Pharmacol. 154(5) , 1009-15, (2008)

Leptin regulates energy expenditure and body weight by acting both on the hypothalamus and on peripheral targets. Central actions of leptin are enhanced by cholecystokinin (CCK). The interaction betwe...

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