TY - JOUR
T1 - Metabotropic glutamate receptors as targets for analgesia
T2 - Antagonism, activation, and allosteric modulation
AU - Montana, Michael C.
AU - Gereau IV, Robert W.
PY - 2011/10
Y1 - 2011/10
N2 - 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. Glutamate, the primary excitatory neurotransmitter in the vertebrate nervous system, mediates its effects via activation of two main classes of receptors: ligand-gated ion channels known as ionotropic receptors and G-protein coupled metabotropic receptors. Antagonists of ionotropic glutamate receptors, such as ketamine, have robust analgesic properties; however, their analgesic utility is limited to monitored clinical settings due to the potential for psychomimetic effects.
AB - 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. Glutamate, the primary excitatory neurotransmitter in the vertebrate nervous system, mediates its effects via activation of two main classes of receptors: ligand-gated ion channels known as ionotropic receptors and G-protein coupled metabotropic receptors. Antagonists of ionotropic glutamate receptors, such as ketamine, have robust analgesic properties; however, their analgesic utility is limited to monitored clinical settings due to the potential for psychomimetic effects.
KW - Analgesia
KW - Pain
KW - Sensitization
KW - mGluR
UR - http://www.scopus.com/inward/record.url?scp=80053505880&partnerID=8YFLogxK
U2 - 10.2174/138920111798357438
DO - 10.2174/138920111798357438
M3 - Article
C2 - 21466446
AN - SCOPUS:80053505880
VL - 12
SP - 1681
EP - 1688
JO - Current Pharmaceutical Biotechnology
JF - Current Pharmaceutical Biotechnology
SN - 1389-2010
IS - 10
ER -