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Naunyn Schmiedebergs Arch Pharmacol
2015 May 01;3885:509-16. doi: 10.1007/s00210-015-1085-6.
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Potencies and unblocking kinetic properties of antagonists at recombinant human NMDA receptors in a Xenopus oocytes model.
Heusler P
,
Tourette A
,
Cussac D
.
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N-methyl-D-aspartate (NMDA) receptor channels are implicated in a wide range of physiological and pathophysiological processes, and a large number of pharmacological agents have been introduced that target the receptor via diverse mechanisms of action. Amongst others, subunit selectivity (in particular for the NR2B receptor subunit) and rapid unblocking kinetics have been put forward as favourable pharmacological properties of NMDA receptor-targeting drugs. Here, we describe a pharmacological characterization of human recombinant NMDA receptors expressed in Xenopus oocytes in an electrophysiological set-up. Using this approach, we compare inhibitor potencies of several known NMDA receptor ligands as well as unblocking kinetic properties of selected compounds. All compounds tested had similar potencies at receptors containing NR2A or NR2B receptors with the exception of traxoprodil, which was selective for NR2B. The rank order of potency was (+)MK-801 > phencyclidine (PCP) ≈ traxoprodil > memantine ≈ ketamine > duloxetine. In line with its proposed rapid dissociation properties, the relatively well-tolerated drug memantine exhibits markedly faster unblocking than ketamine and PCP, similar to the low-affinity compound, duloxetine. Electrophysiological recording in Xenopus oocytes thus allows a relatively convenient comparison of key pharmacological parameters at recombinant human NMDA receptors.
Balu,
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2015, Pubmed
Balu,
The NMDA receptor 'glycine modulatory site' in schizophrenia: D-serine, glycine, and beyond.
2015,
Pubmed
Calabrese,
Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.
2012,
Pubmed
Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed
Donevan,
Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate receptors.
2000,
Pubmed
,
Xenbase
Dravid,
Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block.
2007,
Pubmed
,
Xenbase
Feng,
Structure-activity analysis of a novel NR2C/NR2D-preferring NMDA receptor antagonist: 1-(phenanthrene-2-carbonyl) piperazine-2,3-dicarboxylic acid.
2004,
Pubmed
,
Xenbase
Feuerbach,
Comparative pharmacology of the human NMDA-receptor subtypes R1-2A, R1-2B, R1-2C and R1-2D using an inducible expression system.
2010,
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Ghasemi,
The role of NMDA receptors in the pathophysiology and treatment of mood disorders.
2014,
Pubmed
Gilling,
Potency, voltage-dependency, agonist concentration-dependency, blocking kinetics and partial untrapping of the uncompetitive N-methyl-D-aspartate (NMDA) channel blocker memantine at human NMDA (GluN1/GluN2A) receptors.
2009,
Pubmed
Hess,
Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors.
1996,
Pubmed
,
Xenbase
Heusler,
Differential ion current activation by human 5-HT(1A) receptors in Xenopus oocytes: evidence for agonist-directed trafficking of receptor signalling.
2005,
Pubmed
,
Xenbase
Johnson,
Mechanism of action of memantine.
2006,
Pubmed
Lai,
Stroke intervention pathways: NMDA receptors and beyond.
2011,
Pubmed
Lipton,
Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond.
2006,
Pubmed
Mony,
Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential.
2009,
Pubmed
Mott,
Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition.
1998,
Pubmed
,
Xenbase
Nagata,
Direct inhibition of N-methyl-D-aspartate (NMDA)-receptor function by antiglaucomatous beta-antagonists.
2008,
Pubmed
,
Xenbase
Paoletti,
NMDA receptor subunits: function and pharmacology.
2007,
Pubmed
Paoletti,
NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease.
2013,
Pubmed
Parsons,
Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo.
1995,
Pubmed
Petrenko,
Defining the role of NMDA receptors in anesthesia: are we there yet?
2014,
Pubmed
Planells-Cases,
A novel N-methyl-D-aspartate receptor open channel blocker with in vivo neuroprotectant activity.
2002,
Pubmed
,
Xenbase
Preskorn,
An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder.
2008,
Pubmed
Sanacora,
Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders.
2012,
Pubmed
Tarawneh,
Potential future neuroprotective therapies for neurodegenerative disorders and stroke.
2010,
Pubmed
Traynelis,
Glutamate receptor ion channels: structure, regulation, and function.
2010,
Pubmed
Wang,
Block of neuronal Na+ channels by antidepressant duloxetine in a state-dependent manner.
2010,
Pubmed
Williams,
Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors.
1993,
Pubmed
,
Xenbase
de Bartolomeis,
Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia.
2012,
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