Analgesic activity of metabotropic glutamate receptor 1 antagonists on spontaneous post-operative pain in rats

Zhu, Chang; Baker, Scott J.; EI-Kouhen, Odile; Lehto, Sonya G.; Hollingsworth, Peter R.; Gauvin, Donna M.; Hernandez, Gricelda; Zheng, Guo-Zhu; Chang, Ruidong; Moreland, Robert B.; Stewart, Andrew O.; Brioni, Jorge D.; Honoré, Prisca

doi:10.1016/j.ejphar.2007.09.047

Cited by 23 publications

(13 citation statements)

References 38 publications

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“…The negative mGlu1 receptor modulator A-841720 in Table 6 significantly attenuated postoperative pain after paw skin incision in rats with an ED 50 of 10 mol/kg i.p. ; some close derivatives of the compound were also active in that model (Zhu et al, 2008). Motor side effects were observed at 3-to 10-fold higher doses.…”

Section: Allosteric Modulators Of the Mglu1 Receptor A Negative Allomentioning

confidence: 81%

Allosteric Modulation of Family C G-Protein-Coupled Receptors: from Molecular Insights to Therapeutic Perspectives

2011

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Section: Allosteric Modulators Of the Mglu1 Receptor A Negative Allomentioning

confidence: 81%

Allosteric Modulation of Family C G-Protein-Coupled Receptors: from Molecular Insights to Therapeutic Perspectives

2011

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“…In addition, systemic administration of the non-competitive mGluR1 antagonist, A841720, has been reported to reverse inflammatory and neuropathic pain in rodents, further supporting a therapeutic potential of mGluR1 antagonism in the treatment of chronic pain states [347,348]. Several other non-competitive mGluR1 antagonists, such as A841720, A794282, A794278 and A850002, have also been reported to attenuate spontaneous nociception in a pre-clinical model of postoperative pain [349]. Beside these pharmacological evidences, antisense knockdown of mGluR1 receptors has been reported to decrease spinal nociceptive neurotransmission and neuropathic hyperalgesia [334,336,337], further strengthening the antinociceptive potential of mGluR1 blockade.…”

Section: Painmentioning

confidence: 99%

Therapeutic Potential of Metabotropic Glutamate Receptor Modulators

Hovelsø

Sotty²,

Montezinho³

et al. 2012

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Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) and is a major player in complex brain functions. Glutamatergic transmission is primarily mediated by ionotropic glutamate receptors, which include NMDA, AMPA and kainate receptors. However, glutamate exerts modulatory actions through a family of metabotropic G-protein-coupled glutamate receptors (mGluRs). Dysfunctions of glutamatergic neurotransmission have been implicated in the etiology of several diseases. Therefore, pharmacological modulation of ionotropic glutamate receptors has been widely investigated as a potential therapeutic strategy for the treatment of several disorders associated with glutamatergic dysfunction. However, blockade of ionotropic glutamate receptors might be accompanied by severe side effects due to their vital role in many important physiological functions. A different strategy aimed at pharmacologically interfering with mGluR function has recently gained interest. Many subtype selective agonists and antagonists have been identified and widely used in preclinical studies as an attempt to elucidate the role of specific mGluRs subtypes in glutamatergic transmission. These studies have allowed linkage between specific subtypes and various physiological functions and more importantly to pathological states. This article reviews the currently available knowledge regarding the therapeutic potential of targeting mGluRs in the treatment of several CNS disorders, including schizophrenia, addiction, major depressive disorder and anxiety, Fragile X Syndrome, Parkinson’s disease, Alzheimer’s disease and pain.

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“…However the significant motor impairment exhibited by mGlu1 knockout mice [48] as well as the findings that mGlu1 antagonists can decrease locomotor activity and impair rotarod performance [49], indicate that care may be needed when administering systemically active mGlu1 antagonists.…”

Section: Metabotropic Glutamate Receptors In Painmentioning

confidence: 99%

Metabotropic Glutamate Receptors as Targets for Analgesia: Antagonism, Activation, and Allosteric Modulation

Montana¹,

Gereau²

2011

CPB

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The metabotropic glutamate receptors (mGluRs) are expressed pre- and post-synaptically throughout the nervous system where they serve as modulators of synaptic transmission and neuronal excitability. Activation of mGluRs can be pro- or anti-nociceptive, depending on their anatomic location and the signaling cascades to which they couple. Antagonists of Group I mGluRs and agonists of Group II and III mGluRs have shown therapeutic promise in animal pain models. This article reviews the potential therapeutic utility of several agents that act predominantly via mGluRs, specifically focusing on their analgesic efficacy and discussing possible off-target effects.

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Analgesic activity of metabotropic glutamate receptor 1 antagonists on spontaneous post-operative pain in rats

Cited by 23 publications

References 38 publications

Allosteric Modulation of Family C G-Protein-Coupled Receptors: from Molecular Insights to Therapeutic Perspectives

Allosteric Modulation of Family C G-Protein-Coupled Receptors: from Molecular Insights to Therapeutic Perspectives

Therapeutic Potential of Metabotropic Glutamate Receptor Modulators

Metabotropic Glutamate Receptors as Targets for Analgesia: Antagonism, Activation, and Allosteric Modulation

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