2-[[[1-(7-氯-4-喹啉)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-基]羰基]氨基]-三环[3.3.1.13,7]癸烷-2-羧酸

用途

Meclinertant (SR 48692) 是一种有效的,选择性的,非肽和口服活性神经降压素受体 (NTS1) 拮抗剂。在人结肠癌细胞中,Meclinertant 竞争性拮抗神经降压素诱导的细胞内 Ca2+ 动员,pA2 值为 8.13。Meclinertant 具有抗焦虑,抗上瘾和记忆障碍的作用。

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名称

[ CAS 号 ]:
146362-70-1

[ 中文名 ]:
2-[[[1-(7-氯-4-喹啉)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-基]羰基]氨基]-三环[3.3.1.13,7]癸烷-2-羧酸

[ 英文名 ]:
SR 48692

[英文别名 ]:

Reminertant
merclinertant
SR48692
UNII-5JBP4SI96H
Meclinertant

生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 神经降压素受体

研究领域 >> 神经疾病

[ 靶点 ]

Neurotensin receptor 1 (NTS1)[1]

[体外研究]

在体外,Meclientant(SR 48692)竞争性地抑制125I标记的神经降压素与不同物种脑组织中的高亲和力结合位点的结合,IC50值分别为0.99 nM(豚鼠)、4.0 nM(大鼠中脑细胞)、7.6 nM(转染克隆的高亲和力大鼠脑受体的COS-7细胞),13.7nm(新生小鼠脑)、17.8nm(新生人脑)、8.7nm(成年人脑)和30.3nm(HT-29细胞)。Meclientant也能从低亲和力的左旋卡托斯汀敏感结合位点置换125I标记的神经降压素,但浓度较高(成年小鼠脑34.8nm,成年大鼠脑82.0nm)[1]。在豚鼠纹状体切片中,Meclientant阻断了神经降压素刺激的[3H]多巴胺的K+诱发释放,其强度(IC50=0.46 nM)与其结合亲和力相关[1]。

[体内研究]

meclientant(SR 48692)在80μg/kg剂量下逆转了纹状体内注射神经降压素诱导的小鼠转身行为,并具有较长的作用时间(6小时)[1]。

[参考文献]

[1]. Gully D, et al. Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):65-9.

[2]. Griebel G, et al. Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery. Neurosci Biobehav Rev. 2001 Dec;25(7-8):619-26.

[3]. Felszeghy K, et al. Neurotensin receptor antagonist administered during cocaine withdrawal decreases locomotor sensitization and conditioned place preference. Neuropsychopharmacology. 2007 Dec;32(12):2601-10.

物理化学性质

[ 密度 ]:
1.5±0.1 g/cm3

[ 沸点 ]:
781.2±60.0 °C at 760 mmHg

[ 分子式 ]:
C₃₂H₃₁ClN₄O₅

[ 分子量 ]:
587.065

[ 闪点 ]:
426.2±32.9 °C

[ 精确质量 ]:
586.198303

[ PSA ]:
119.06000

[ LogP ]:
4.55

[ 蒸汽压 ]:
0.0±2.8 mmHg at 25°C

[ 折射率 ]:
1.729

[ 储存条件 ]:
-20°C

MSDS

详细MSDS(安全技术说明书)

安全信息

[ RTECS号 ]:
YD1988500

合成路线

详细合成路线

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文献

Neurotensin in the ventral pallidum increases extracellular gamma-aminobutyric acid and differentially affects cue- and cocaine-primed reinstatement.

J. Pharmacol. Exp. Ther. 325(2) , 556-66, (2008)

Cocaine-primed reinstatement is an animal model of drug relapse. The neurocircuitry underlying cocaine-primed reinstatement includes a decrease in GABA in the ventral pallidum (VP) that is inhibited b...

Hypothalamic neurotensin projections promote reward by enhancing glutamate transmission in the VTA.

J. Neurosci. 33(18) , 7618-26, (2013)

The lateral hypothalamus (LH) sends a dense glutamatergic and peptidergic projection to dopamine neurons in the ventral tegmental area (VTA), a cell group known to promote reinforcement and aspects of...

The role of neurotensin in positive reinforcement in the rat central nucleus of amygdala.

Behav. Brain Res. 208(2) , 430-5, (2010)

In the central nervous system neurotensin (NT) acts as a neurotransmitter and neuromodulator. It was shown that NT has positive reinforcing effects after its direct microinjection into the ventral teg...

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