Document Detail


Antinociceptive mechanism of the spirocyclopiperazinium compound LXM-10 in mice and rats.
MedLine Citation:
PMID:  20100504     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Drugs typically used to treat pain are limited by their undesirable side effects, which has prompted a search for mechanistically different analgesic agents. We report the antinociception effect of the spirocyclopiperazinium compound LXM-10 via activation of peripheral alpha7 nicotinic and muscarinic acetylcholine receptors in mice. This effect was attenuated by hexamethonium, atropine methylnitrate, methyllycaconitine citrate, tropicamide, bicuculline, and phaclofen. Competition receptor-binding assays in vitro showed that LXM-10 binds with high affinity alpha7 nAchR and with low affinity M4 receptors. Our findings show that the antinociception signaling pathway of LXM-10 underlies activation of peripheral alpha7 nicotinic and possibly of M4 muscarinic receptors, which activate GABA(A) and GABA(B) receptors, resulting in antinociceptive effects without obvious side effects.
Authors:
Yulan Xiong; Xia Zhao; Qi Sun; Runtao Li; Changling Li; Jia Ye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-25
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  95     ISSN:  1873-5177     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-01     Completed Date:  2010-07-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  192-7     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China.
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MeSH Terms
Descriptor/Qualifier:
Analgesics / pharmacology*
Animals
Female
Male
Mice
Mice, Inbred C57BL
Piperazines / pharmacology*
Rats
Rats, Wistar
Receptors, Muscarinic / drug effects
Receptors, Nicotinic / drug effects
Spiro Compounds / pharmacology*
Chemical
Reg. No./Substance:
0/2,4-dimethyl-9-beta-phenylethyl-3-oxo-6, 9-diazaspiro(5.5)undecane chloride; 0/Analgesics; 0/Piperazines; 0/Receptors, Muscarinic; 0/Receptors, Nicotinic; 0/Spiro Compounds

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