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学科主题: 药学
题名:
Anti-inflammatory effect of the spirocyclopiperazinium compound LXM-10 in mice and rats
作者: 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
发表日期: 2010-01-25
DOI: 10.1016/j.ejphar.2009.10.003
卷: 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
所属项目编号: NSFC 20772009
项目资助者: National Science Foundation of China
WOS记录号: WOS:000274090800028
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52636
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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