Document Detail

Analgesic effects of mGlu1 and mGlu5 receptor antagonists in the rat formalin test.
MedLine Citation:
PMID:  16793067     Owner:  NLM     Status:  MEDLINE    
mGlu1 and mGlu5 receptors have been implicated in pain associated with inflammation. In the present study, the formalin test was used to measure sustained pain with components of tissue injury. The aims of the present study were to assess: (i) the role of mGlu1 and mGlu5 receptors in inflammatory pain using selective antagonist EMQMCM, 1.25-5 mg/kg, as the mGlu1 receptor antagonist, and MPEP or MTEP, 2.5-10 mg/kg, as mGlu5 receptor antagonist; (ii) the possible interaction between mGlu1 and mGlu5 receptor antagonists and morphine; and (iii) whether tolerance develops to the analgesic effects of these antagonists after prolonged treatment. EMQMCM, MTEP and MPEP significantly reduced the manifestation of both phases of formalin response. However, all these mGlu receptor antagonists did not affect the withdrawal latencies in a model of acute pain (Hargreaves test), which has a different underlying mechanism. In the present study, the suppressive effect on formalin-induced pain behaviour was much stronger when mGlu1 and mGlu5 receptor antagonists were co-injected compared to administration of a single antagonist, but this effect was not seen when mGlu receptor antagonist was co-administered with morphine. This is in contrast to the pronounced inhibitory effects after co-treatment with morphine and the uncompetitive NMDA receptor antagonist memantine. The present study also provides the first direct in vivo evidence that prolonged administration of MTEP (5 mg/kg) over 7 days leads to the development of tolerance to its antinociceptive effects. Such tolerance was not observed when EMQMCM (5 mg/kg) was administered in the same manner. In conclusion, these results provide additional arguments for the role of group I mGlu receptors in pain with inflammatory conditions.
N Sevostianova; W Danysz
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2006-06-21
Journal Detail:
Title:  Neuropharmacology     Volume:  51     ISSN:  0028-3908     ISO Abbreviation:  Neuropharmacology     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-21     Completed Date:  2006-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  623-30     Citation Subset:  IM    
Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfurt/Main, Germany.
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MeSH Terms
Analgesics / therapeutic use*
Analysis of Variance
Behavior, Animal
Dose-Response Relationship, Drug
Drug Interactions
Drug Tolerance
Morphine / therapeutic use
Pain / chemically induced,  drug therapy*
Pain Measurement / methods
Pain Threshold / drug effects
Pyridines / therapeutic use
Quinolines / therapeutic use
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / antagonists & inhibitors*,  physiology
Thiazoles / therapeutic use
Reg. No./Substance:
0/(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate; 0/3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; 0/6-methyl-2-(phenylethynyl)pyridine; 0/Analgesics; 0/Pyridines; 0/Quinolines; 0/Receptors, Metabotropic Glutamate; 0/Thiazoles; 0/metabotropic glutamate receptor 5; 0/metabotropic glutamate receptor type 1; 50-00-0/Formaldehyde; 57-27-2/Morphine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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