Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels.

Huettner, James E.; Bean, Bruce P.

doi:10.1073/pnas.85.4.1307

Cited by 609 publications

(469 citation statements)

References 34 publications

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“…However, the relative differences for memantine and MK-801 are likely to be similar to those reported previously for Trff upon removal of these antagonists (Huettner & Bean, 1988;Karschin et al, 1988;Chen et al, 1992;Parsons et al, 1993;1995b). As such, it can be assumed that the very slow open channel blocker MK-801 would still be able to leave the NMDA channel only after several seconds of depolarization and that the degree of relief would, in any case, be very small.…”

Section: Discussionmentioning

confidence: 46%

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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

Frankiewicz

Potier

Bashir

et al. 1996

British J Pharmacology

123

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Section: Discussionmentioning

confidence: 46%

“…However, such experiments were not feasible and, more importantly, not relevant to the questions addressed in the present study on the basis of kinetic data (e.g. Huettner & Bean, 1988;Parsons et al, 1995b) slow blockers such as MK-801 would have little chance to attain new equilibrium binding states during the induction phase of LTP.…”

Section: Discussionmentioning

confidence: 99%

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

Frankiewicz

Potier

Bashir

et al. 1996

British J Pharmacology

123

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“…It has been reported that the NMDA receptor specific antagonist MK801 blocked NMDA receptor channels at the inner part, and had a selective binding to the opening mode. 19 Ketamine (an NMDA receptor nonspecific antagonist) decreases the opening frequency and duration of NMDA receptor channels in a concentration-dependent manner. 20 Accordingly, thiopental sodium may possibly decrease the opening frequency and duration of NMDA receptor channels.…”

Section: Discussionmentioning

confidence: 99%

Effect of thiopental sodium on N-methyl-D-aspartate-gated currents

Liu

Ti-jun

Yao

2006

Can J Anesth/J Can Anesth

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Purpose: N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function.Methods: Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 µM NMDA were applied 100 µm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred µM NMDA alone (control) or NMDA with different concentrations (10-1000 µM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 µM were applied 100 µm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined.Results: N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 µM AP5. The maximal amplitude of NMDAinduced current was 1.15 ± 0.27 nA. The EC50 of NMDA was 53.6 ± 12.4 µM. The NMDA (100 µM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 ± 6.1 µM. Under the effect of 33.6 µM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 ± 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 ± 15 µM, which was greater than that of NMDA without thiopental sodium (P < 0.01). Conclusions:Thiopental sodium decreases NMDA-gated currents in acutely dissociated rat prefrontal cortical pyramidal neurons in a concentration-dependent manner. Objectif : Les récepteurs de N-méthyl-D-aspartate (NMDA) dans le cortex préfrontal (CPF) sont en lien étroit avec l'excitabilité des neurones pyramidaux et la fonction du CPF. L'effet du thio-

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“…NMDA receptor channel blockers represent one group of pharmacologically active agents able to antagonize NMDA receptor activation by acting directly on the phencyclidine recognition site within the channel. Since these agents act in a 'use-dependent' manner, only blocking the channel in the open state (Foster and Wong, 1987;Huettner and Bean, 1988), they have been termed uncompetitive NMDA receptor antagonists.…”

Section: Introductionmentioning

confidence: 99%

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Marvanová

Lakso

Wong

2004

Neuropsychopharmacol

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In this study, we monitored gene expression profiles using cDNA microarrays after an acute systemic administration of the high affinity N-methyl-D-aspartate (NMDA) uncompetitive antagonist MK-801 (1 mg/kg; 4 h), and the clinically used moderate affinity antagonist memantine (25 mg/kg; 4 h) in adult rat brains. From a microarray containing 1090 known genes, 13 genes were regulated by both treatments of which 12 were upregulated and one was downregulated. In addition, 28 and 34 genes were regulated (X1.5-or p0.67-fold change) by either memantine or MK-801, respectively. Genes commonly regulated by both treatments and not previously reported were confirmed by in situ hybridization (ISH) and include regenerating liver inhibitory factor-1 (RL/IF-1), GDP-dissociation inhibitor 1 (GDI-1), neural visinin Ca 2 þ -binding protein 2 (NVP-2), neuromedin B receptor, and Na þ /K þ transporting ATPase 2b. ISH with memantine (5-50 mg/kg) revealed regulation of these genes in other cortical and hippocampal regions. RL/IF-1 induction occurred at 1 h and returned to basal levels by 8 h, consistent with the profile of an immediate early gene. Western blot analysis showed increases (B30-65%) in GDI-1 protein present in both cytosolic and membrane fractions that were significant in the 84-kDa Rab bound form, suggesting that memantine influences Ras-like GTPase function. Genes regulated by a 5 mg/kg dose of memantine might be important in its therapeutic effects. These findings increase the number of known, differentially altered genes after treatment of uncompetitive NMDA receptor antagonists and suggest broader actions of these agents than previously realized.

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Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels.

Abstract: Whole-cell and single-channel recording techniques were used to study the action of the anticonvulsant drug MK-801 {( + )-5-methyl-10,11-dihydro-5H-dibenzo [a,

Cited by 609 publications

References 34 publications

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

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

Effect of thiopental sodium on N-methyl-D-aspartate-gated currents

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

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