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Anti-inflammatory effect of the spirocyclopiperazinium compound LXM-10 in mice and rats
Xiong, Yulan2,5; Ye, Jia1,2; Sun, Qi3; Zhao, Xia1; Li, Runtao3; Jiang, Yimin4
关键词Lxm-10 Anti-inflammation Alpha 7 Nicotinic Acetylcholine Receptor m(4) Muscarine Acetylcholine Receptor
刊名EUROPEAN JOURNAL OF PHARMACOLOGY
2010-01-25
DOI10.1016/j.ejphar.2009.10.003
626期:2-3页:290-296
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]SYSTEMIC INFLAMMATORY RESPONSE ; KINASE INHIBITOR ; VAGUS NERVE ; RECEPTORS ; CYCLOOXYGENASE-2 ; MECHANISM ; PATHWAY ; STIMULATION ; AGONIST ; MODELS
英文摘要

Anti-inflammatory drugs are clinically limited because of their side effects. The aim of this study was to evaluate the anti-inflammatory activities and mechanisms of the spirocyclopiperazinium compound LXM-10 (2, 4-dimethyl-9-beta-phenylethyl-3-oxo-6, 9-diazaspiro[5.5]undecane chloride). We found that LXM-10 produced a significant, dose-dependent decrease in xylene- and carrageenin-induced edema. The anti-inflammatory effect was attenuated by hexamethonium, methyllycaconitine citrate, atropine methylnitrate. and tropicamide. The serum level of TNF-alpha was reduced by LXM-10 in lipopolysaccharide-challenged mice, and this effect was also inhibited by methyllycaconitine and tropicamide. LXM-10 also reduced the prostaglandin E(2) concentration in rat paw tissue. LXM-10 minimised the carrageenin-induced pathological changes and did not affect mice heart rate. LXM-10 did not induce significant changes in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) activity. Median lethal dose (LD(50)) of LXM-10 was 1573.0 mu mol/kg. Our findings suggest that LXM-10 has anti-inflammatory effects by activating alpha 7 nicotinic and M(4) muscarinic acetylcholine receptors with limited side effects. (C) 2009 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000274090800028
项目编号NSFC 20772009
资助机构National Science Foundation of China
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52636
专题北京大学药学院
北京大学医学部管理机构_医学部
北京大学药学院_化学生物学系
北京大学药学院_分子与细胞药理学系
北京大学精神卫生研究所_药房
作者单位1.Peking Univ, Inst Mental Hlth, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, Beijing 100191, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
4.Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, Beijing 100191, Peoples R China
5.Peking Univ, Med & Healthy Anal Ctr, Beijing 100191, Peoples R China
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GB/T 7714
Xiong, Yulan,Ye, Jia,Sun, Qi,et al. Anti-inflammatory effect of the spirocyclopiperazinium compound LXM-10 in mice and rats[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2010,626(2-3):290-296.
APA Xiong, Yulan,Ye, Jia,Sun, Qi,Zhao, Xia,Li, Runtao,&Jiang, Yimin.(2010).Anti-inflammatory effect of the spirocyclopiperazinium compound LXM-10 in mice and rats.EUROPEAN JOURNAL OF PHARMACOLOGY,626(2-3),290-296.
MLA Xiong, Yulan,et al."Anti-inflammatory effect of the spirocyclopiperazinium compound LXM-10 in mice and rats".EUROPEAN JOURNAL OF PHARMACOLOGY 626.2-3(2010):290-296.
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