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J Neural Transm (Vienna)
2008 Oct 01;11510:1367-73. doi: 10.1007/s00702-008-0087-7.
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Blocking kinetics of memantine on NR1a/2A receptors recorded in inside-out and outside-out patches from Xenopus oocytes.
Parsons CG
,
Gilling KE
,
Jatzke C
.
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Previous experiments on primary cultures of hippocampal/cortical neurones revealed that the block and unblock of N-Methyl-D-Aspartate (NMDA) receptor channels by memantine showed double exponential kinetics and that the offset kinetics following a voltage-step were much faster than following a concentration jump. There are, however, two major problems when using such cultured primary neurones for these experiments (1) the almost certain expression of heterogeneous NMDA receptor subunits which could underlie double exponential kinetics due to different potencies at receptor subtypes and (2) slow space- and concentration-clamp due to neuronal morphology which could mask even faster kinetics. Therefore, we performed similar experiments with Xenopus oocytes exclusively expressing one NMDA receptor type (NR1a/2A) at high levels which allowed recordings from membrane patches with large currents. The use of inside-out patches for voltage-step and outside-out patches in combination with a piezo driven fast application system largely negated potential space- and concentration-clamp problems. Block and unblock of the NMDA receptor by memantine after both voltage jump and concentration jumps showed triple exponential kinetics. The fast onset kinetics of NMDA receptor channel block following both concentration-clamp and voltage jumps from +70 to -70 mV were similar. In contrast, offset kinetics after a voltage-step from -70 to +70 mV were much faster than following a concentration jump at the holding potential of -70 mV. These results provide further support for the hypothesis that rapid relief of block via strong synaptic membrane depolarisation underlies the good therapeutic profile of memantine.
Areosa,
Memantine for dementia.
2005,
Pubmed
Blanpied,
Amantadine inhibits NMDA receptors by accelerating channel closure during channel block.
2005,
Pubmed
Blanpied,
Trapping channel block of NMDA-activated responses by amantadine and memantine.
1997,
Pubmed
Bresink,
Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cells.
1996,
Pubmed
Chen,
Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity.
1992,
Pubmed
Danysz,
Neuroprotective and symptomatological action of memantine relevant for Alzheimer's disease--a unified glutamatergic hypothesis on the mechanism of action.
2000,
Pubmed
Danysz,
The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence.
2003,
Pubmed
Frankiewicz,
Effects of memantine and MK-801 on NMDA-induced currents in cultured neurones and on synaptic transmission and LTP in area CA1 of rat hippocampal slices.
1996,
Pubmed
Gilling,
Agonist concentration dependency of blocking kinetics but not equilibrium block of N-methyl-D-aspartate receptors by memantine.
2007,
Pubmed
Green,
NMDA receptors formed by NR1 in Xenopus laevis oocytes do not contain the endogenous subunit XenU1.
2002,
Pubmed
,
Xenbase
Kornhuber,
Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study.
1991,
Pubmed
Kornhuber,
Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex.
1989,
Pubmed
Laube,
Molecular determinants of ligand discrimination in the glutamate-binding pocket of the NMDA receptor.
2004,
Pubmed
Li,
East meets West in the search for Alzheimer's therapeutics - novel dimeric inhibitors from tacrine and huperzine A.
2007,
Pubmed
Parsons,
Amino-alkyl-cyclohexanes are novel uncompetitive NMDA receptor antagonists with strong voltage-dependency and fast blocking kinetics: in vitro and in vivo characterization.
1999,
Pubmed
,
Xenbase
Parsons,
Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan).
1993,
Pubmed
Parsons,
Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist--a review of preclinical data.
1999,
Pubmed
Parsons,
Budipine is a low affinity, N-methyl-D-aspartate receptor antagonist: patch clamp studies in cultured striatal, hippocampal, cortical and superior colliculus neurones.
1998,
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
Peskind,
Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial.
2006,
Pubmed
Rammes,
Interactions of GYKI 52466 and NBQX with cyclothiazide at AMPA receptors: experiments with outside-out patches and EPSCs in hippocampal neurones.
1998,
Pubmed
Reisberg,
Memantine in moderate-to-severe Alzheimer's disease.
2003,
Pubmed
Rogawski,
Therapeutic potential of excitatory amino acid antagonists: channel blockers and 2,3-benzodiazepines.
1993,
Pubmed
Schmidt,
Revisiting the postulated "unitary glutamate receptor": electrophysiological and pharmacological analysis in two heterologous expression systems fails to detect evidence for its existence.
2006,
Pubmed
,
Xenbase
Sobolevsky,
Two blocking sites of amino-adamantane derivatives in open N-methyl-D-aspartate channels.
1998,
Pubmed
Sobolevsky,
Interaction of memantine and amantadine with agonist-unbound NMDA-receptor channels in acutely isolated rat hippocampal neurons.
1998,
Pubmed
Tariot,
Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.
2004,
Pubmed
Wang,
Modulation by magnesium of the affinity of NMDA receptors for glycine in murine hippocampal neurones.
1995,
Pubmed