LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article ; Online: The role of Loop F in the activation of the GABA receptor.

Khatri, Alpa / Weiss, David S

2010 Volume 588, Issue Pt 1, Page(s) 59–66

Abstract: Functional studies of the ligand gated ion channel family (nicotinic acetylcholine, serotonin Type 3, glycine and GABA receptors) along with the crystal structure of the acetylcholine binding protein (AChBP) and molecular dynamics simulations of the ... ...

Abstract	Functional studies of the ligand gated ion channel family (nicotinic acetylcholine, serotonin Type 3, glycine and GABA receptors) along with the crystal structure of the acetylcholine binding protein (AChBP) and molecular dynamics simulations of the nAChR structure have resulted in a structural model in which the agonist-binding pocket comprises six loops (A-F) contributed by adjacent subunits. It is presumed that the binding of agonist results in a local structural rearrangement that is then transduced to the gate, causing the pore to open. Efforts are underway to better define the specific roles of the six binding loops. Several studies have suggested Loop F may play a direct role in linking the structural rearrangement within the binding pocket to the gate, although other investigations have indicated Loop F may be crucial for locking the agonist molecule into the binding site. This review will focus on the controversy surrounding the role of Loop F during GABA receptor activation.
MeSH term(s)	Animals ; Computer Simulation ; Humans ; Ion Channel Gating ; Models, Chemical ; Models, Molecular ; Protein Conformation ; Protein Structure, Tertiary ; Protein Subunits ; Receptors, GABA/chemistry ; Receptors, GABA/ultrastructure ; Structure-Activity Relationship
Chemical Substances	Protein Subunits ; Receptors, GABA
Language	English
Publishing date	2010-01-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2009.179705
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.65: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Triheteromeric GluN1/GluN2A/GluN2C NMDARs with Unique Single-Channel Properties Are the Dominant Receptor Population in Cerebellar Granule Cells.

Bhattacharya, Subhrajit / Khatri, Alpa / Swanger, Sharon A / DiRaddo, John O / Yi, Feng / Hansen, Kasper B / Yuan, Hongjie / Traynelis, Stephen F

Neuron

2018 Volume 99, Issue 2, Page(s) 315–328.e5

Abstract: NMDA-type glutamate receptors (NMDARs) are ligand-gated ion channels that mediate excitatory neurotransmission in the CNS. Here we describe functional and single-channel properties of triheteromeric GluN1/GluN2A/GluN2C receptors, which contain two GluN1, ...

Abstract	NMDA-type glutamate receptors (NMDARs) are ligand-gated ion channels that mediate excitatory neurotransmission in the CNS. Here we describe functional and single-channel properties of triheteromeric GluN1/GluN2A/GluN2C receptors, which contain two GluN1, one GluN2A, and one GluN2C subunits. This NMDAR has three conductance levels and opens in bursts similar to GluN1/GluN2A receptors but with a single-channel open time and open probability reminiscent of GluN1/GluN2C receptors. The deactivation time course of GluN1/GluN2A/GluN2C receptors is intermediate to GluN1/GluN2A and GluN1/GluN2C receptors and is not dominated by GluN2A or GluN2C. We show that triheteromeric GluN1/GluN2A/GluN2C receptors are the predominant NMDARs in cerebellar granule cells and propose that co-expression of GluN2A and GluN2C in cerebellar granule cells occludes cell surface expression of diheteromeric GluN1/GluN2C receptors. This new insight into neuronal GluN1/GluN2A/GluN2C receptors highlights the complexity of NMDAR signaling in the CNS.
MeSH term(s)	Animals ; Cerebellum/cytology ; Cerebellum/drug effects ; Cerebellum/physiology ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Agonists/pharmacology ; Female ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins/agonists ; Nerve Tissue Proteins/biosynthesis ; Organ Culture Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/agonists ; Receptors, N-Methyl-D-Aspartate/biosynthesis ; Xenopus laevis
Chemical Substances	Excitatory Amino Acid Agonists ; Gprin1 protein, mouse ; NR2C NMDA receptor ; Nerve Tissue Proteins ; Receptors, N-Methyl-D-Aspartate ; N-methyl D-aspartate receptor subtype 2A (VH92ICR8HX)
Language	English
Publishing date	2018-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2018.06.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Potentiation of GluN2C/D NMDA receptor subtypes in the amygdala facilitates the retention of fear and extinction learning in mice.

Ogden, Kevin K / Khatri, Alpa / Traynelis, Stephen F / Heldt, Scott A

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2013 Volume 39, Issue 3, Page(s) 625–637

Abstract: NMDA receptors are glutamate receptor ion channels that contribute to synaptic plasticity and are important for many forms of learning and memory. In the amygdala, NMDA receptors are critical for the acquisition, retention, and extinction of classically ... ...

Abstract	NMDA receptors are glutamate receptor ion channels that contribute to synaptic plasticity and are important for many forms of learning and memory. In the amygdala, NMDA receptors are critical for the acquisition, retention, and extinction of classically conditioned fear responses. Although the GluN2B subunit has been implicated in both the acquisition and extinction of conditioned fear, GluN2C-knockout mice show reduced conditioned fear responses. Moreover, D-cycloserine (DCS), which facilitates fear extinction, selectively enhances the activity of GluN2C-containing NMDA receptors. To further define the contribution of GluN2C receptors to fear learning, we infused the GluN2C/GluN2D-selective potentiator CIQ bilaterally into the basolateral amygdala (3, 10, or 30 μg/side) following either fear conditioning or fear extinction training. CIQ both increased the expression of conditioned fear 24 h later and enhanced the extinction of the previously conditioned fear response. These results support a critical role for GluN2C receptors in the amygdala in the consolidation of learned fear responses and suggest that increased activity of GluN2C receptors may underlie the therapeutic actions of DCS.
MeSH term(s)	Amygdala/drug effects ; Amygdala/metabolism ; Animals ; Area Under Curve ; Benzimidazoles/pharmacology ; Conditioning, Psychological/drug effects ; Conditioning, Psychological/physiology ; Dose-Response Relationship, Drug ; Extinction, Psychological/drug effects ; Extinction, Psychological/physiology ; Fear/drug effects ; Fear/physiology ; Gene Expression Regulation/drug effects ; Male ; Maze Learning/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microinjections ; Motor Activity/drug effects ; Oocytes ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Retention, Psychology/drug effects ; Retention, Psychology/physiology ; Xenopus
Chemical Substances	2-amino-3-methylimidazo(1,2-d)naphthalene ; Benzimidazoles ; NR2C NMDA receptor ; Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2013-09-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/npp.2013.241
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2379: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Biased modulators of NMDA receptors control channel opening and ion selectivity.

Perszyk, Riley E / Swanger, Sharon A / Shelley, Chris / Khatri, Alpa / Fernandez-Cuervo, Gabriela / Epplin, Matthew P / Zhang, Jing / Le, Phuong / Bülow, Pernille / Garnier-Amblard, Ethel / Gangireddy, Pavan Kumar Reddy / Bassell, Gary J / Yuan, Hongjie / Menaldino, David S / Liotta, Dennis C / Liebeskind, Lanny S / Traynelis, Stephen F

Nature chemical biology

2020 Volume 16, Issue 2, Page(s) 188–196

Abstract: Allosteric modulators of ion channels typically alter the transitions rates between conformational states without changing the properties of the open pore. Here we describe a new class of positive allosteric modulators of N-methyl D-aspartate receptors ( ... ...

Abstract	Allosteric modulators of ion channels typically alter the transitions rates between conformational states without changing the properties of the open pore. Here we describe a new class of positive allosteric modulators of N-methyl D-aspartate receptors (NMDARs) that mediate a calcium-permeable component of glutamatergic synaptic transmission and play essential roles in learning, memory and cognition, as well as neurological disease. EU1622-14 increases agonist potency and channel-open probability, slows receptor deactivation and decreases both single-channel conductance and calcium permeability. The unique functional selectivity of this chemical probe reveals a mechanism for enhancing NMDAR function while limiting excess calcium influx, and shows that allosteric modulators can act as biased modulators of ion-channel permeation.
MeSH term(s)	Allosteric Regulation/drug effects ; Animals ; Calcium/metabolism ; Cells, Cultured ; Female ; Glutamic Acid/metabolism ; Glutamic Acid/pharmacology ; Glycine/metabolism ; Glycine/pharmacology ; HEK293 Cells ; High-Throughput Screening Assays/methods ; Humans ; Ion Channel Gating/drug effects ; Mice, Inbred C57BL ; Neurons/drug effects ; Neurons/metabolism ; Oocytes/drug effects ; Oocytes/physiology ; Pyrrolidines/pharmacology ; Receptors, N-Methyl-D-Aspartate/agonists ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Xenopus laevis
Chemical Substances	NR2B NMDA receptor ; Pyrrolidines ; Receptors, N-Methyl-D-Aspartate ; Glutamic Acid (3KX376GY7L) ; Calcium (SY7Q814VUP) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2020-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2202962-X
ISSN	1552-4469 ; 1552-4450
ISSN (online)	1552-4469
ISSN	1552-4450
DOI	10.1038/s41589-019-0449-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6251: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 90: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Structural rearrangements in loop F of the GABA receptor signal ligand binding, not channel activation.

Khatri, Alpa / Sedelnikova, Anna / Weiss, David S

Biophysical journal

2009 Volume 96, Issue 1, Page(s) 45–55

Abstract: Structure-function studies of the Cys loop family of ionotropic neurotransmitter receptors (GABA, nACh, 5-HT(3), and glycine receptors) have resulted in a six-loop (A-F) model of the agonist-binding site. Key amino acids have been identified in these ... ...

Abstract	Structure-function studies of the Cys loop family of ionotropic neurotransmitter receptors (GABA, nACh, 5-HT(3), and glycine receptors) have resulted in a six-loop (A-F) model of the agonist-binding site. Key amino acids have been identified in these loops that associate with, and stabilize, bound ligand. The next step is to identify the structural rearrangements that couple agonist binding to channel opening. Loop F has been proposed to move upon receptor activation, although it is not known whether this movement is along the conformational pathway for channel opening. We test this hypothesis in the GABA receptor using simultaneous electrophysiology and site-directed fluorescence spectroscopy. The latter method reveals structural rearrangements by reporting changes in hydrophobicity around an environmentally sensitive fluorophore attached to defined positions of loop F. Using a series of ligands that span the range from full activation to full antagonism, we show there is no correlation between the rearrangements in loop F and channel opening. Based on these data and agonist docking simulations into a structural model of the GABA binding site, we propose that loop F is not along the pathway for channel opening, but rather is a component of the structural machinery that locks ligand into the agonist-binding site.
MeSH term(s)	Amino Acid Sequence ; Animals ; Binding Sites ; Computer Simulation ; GABA Agonists/chemistry ; GABA Agonists/metabolism ; GABA Antagonists/chemistry ; GABA Antagonists/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Membrane Potentials/genetics ; Membrane Potentials/physiology ; Models, Chemical ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Patch-Clamp Techniques ; Protein Binding ; Protein Conformation ; Rats ; Receptors, GABA/chemistry ; Receptors, GABA/genetics ; Receptors, GABA/metabolism ; Sequence Homology, Amino Acid ; Spectrometry, Fluorescence ; Xenopus laevis ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	GABA Agonists ; GABA Antagonists ; Receptors, GABA ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2009-01-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2008.09.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 235: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 2: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Correction to "Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective potentiators".

Zimmerman, Sommer S / Khatri, Alpa / Garnier-Amblard, Ethel C / Mullasseril, Praseeda / Kurtkaya, Natalie L / Gyoneva, Stefka / Hansen, Kasper B / Traynelis, Stephen F / Liotta, Dennis C

Journal of medicinal chemistry

2015 Volume 58, Issue 6, Page(s) 2862

Language	English
Publishing date	2015-03-26
Publishing country	United States
Document type	Published Erratum
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.5b00199
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾

Article ; Online: Correction to Synthesis and Structure Activity Relationship of Tetrahydroisoquinoline-Based Potentiators of GluN2C and GluN2D Containing N-Methyl-d-aspartate Receptors.

Santangelo Freel, Rose M / Ogden, Kevin K / Strong, Katie L / Khatri, Alpa / Chepiga, Kathryn M / Jensen, Henrik S / Traynelis, Stephen F / Liotta, Dennis C

Journal of medicinal chemistry

2014 Volume 57, Issue 11, Page(s) 4975

Language	English
Publishing date	2014-05-30
Publishing country	United States
Document type	Published Erratum
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/jm500710w
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Structure-activity relationships and pharmacophore model of a noncompetitive pyrazoline containing class of GluN2C/GluN2D selective antagonists.

Acker, Timothy M / Khatri, Alpa / Vance, Katie M / Slabber, Cathryn / Bacsa, John / Snyder, James P / Traynelis, Stephen F / Liotta, Dennis C

Journal of medicinal chemistry

2013 Volume 56, Issue 16, Page(s) 6434–6456

Abstract: Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors ... ...

Abstract	Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors over GluN2A- and GluN2B-containing receptors. Several members of this class inhibit NMDA receptor responses in the nanomolar range and are more than 50-fold selective over GluN1/GluN2A and GluN1/GluN2B NMDA receptors, as well as AMPA, kainate, GABA, glycine, nicotinic, serotonin, and purinergic receptors. Analysis of the purified enantiomers of one of the more potent and selective compounds shows that the S-enantiomer is both more potent and more selective than the R-enantiomer. The S-enantiomer had an IC50 of 0.17-0.22 μM at GluN2D- and GluN2C-containing receptors, respectively, and showed over 70-fold selectivity over other NMDA receptor subunits. The subunit selectivity of this class of compounds should be useful in defining the role of GluN2C- and GluN2D-containing receptors in specific brain circuits in both physiological and pathophysiological conditions.
MeSH term(s)	Blood-Brain Barrier ; Excitatory Amino Acid Antagonists/pharmacology ; Humans ; Microsomes, Liver/metabolism ; Models, Molecular ; Pyrazoles/chemistry ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Structure-Activity Relationship
Chemical Substances	Excitatory Amino Acid Antagonists ; Pyrazoles ; Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2013-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/jm400652r
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Site-specific fluorescence reveals distinct structural changes induced in the human rho 1 GABA receptor by inhibitory neurosteroids.

Li, Ping / Khatri, Alpa / Bracamontes, John / Weiss, David S / Steinbach, Joe Henry / Akk, Gustav

Molecular pharmacology

2010 Volume 77, Issue 4, Page(s) 539–546

Abstract: The rho 1 GABA receptor is inhibited by a number of neuroactive steroids. A previous study (J Pharmacol Exp Ther 323:236-247, 2007) focusing on the electrophysiological effects of inhibitory steroids on the rho 1 receptor found that steroid inhibitors ... ...

Abstract	The rho 1 GABA receptor is inhibited by a number of neuroactive steroids. A previous study (J Pharmacol Exp Ther 323:236-247, 2007) focusing on the electrophysiological effects of inhibitory steroids on the rho 1 receptor found that steroid inhibitors could be divided into three major groups based on how mutations to residues in the M2 transmembrane domain modified inhibition. It was proposed that the steroids act through distinct mechanisms. We selected representatives of the three groups (pregnanolone, tetrahydrodeoxycorticosterone, pregnanolone sulfate, allopregnanolone sulfate, and beta-estradiol) and probed how these steroids, as well as the nonsteroidal inhibitor picrotoxinin, modify GABA-elicited fluorescence changes from the Alexa 546 C5 maleimide fluorophore attached to residues in the extracellular region of the receptor. The fluorophore responds with changes in quantum yield to changes in the environment, allowing it to probe for structural changes taking place during channel activation or modulation. The results indicate that the modulators have specific effects on fluorescence changes suggesting that distinct conformational changes accompany inhibition. The findings are consistent with the steroids acting as allosteric inhibitors of the rho 1 GABA receptor and support the hypothesis that divergent mechanisms underlie the action of inhibitory steroids on the rho 1 GABA receptor.
MeSH term(s)	Dose-Response Relationship, Drug ; Estradiol/pharmacology ; Fluorescence ; GABA-B Receptor Antagonists ; Humans ; Mutation ; Neurotransmitter Agents/pharmacology ; Picrotoxin/analogs & derivatives ; Picrotoxin/pharmacology ; Protein Conformation ; Receptors, GABA-B/chemistry ; Receptors, GABA-B/genetics ; Sesterterpenes ; gamma-Aminobutyric Acid/pharmacology
Chemical Substances	GABA-B Receptor Antagonists ; Neurotransmitter Agents ; Receptors, GABA-B ; Sesterterpenes ; Picrotoxin (124-87-8) ; Estradiol (4TI98Z838E) ; gamma-Aminobutyric Acid (56-12-2) ; picrotoxinin (9K011NUF0R)
Language	English
Publishing date	2010-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/mol.109.062885
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 525: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective potentiators.

Zimmerman, Sommer S / Khatri, Alpa / Garnier-Amblard, Ethel C / Mullasseril, Praseeda / Kurtkaya, Natalie L / Gyoneva, Stefka / Hansen, Kasper B / Traynelis, Stephen F / Liotta, Dennis C

Journal of medicinal chemistry

2014 Volume 57, Issue 6, Page(s) 2334–2356

Abstract: NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A-D subunits that mediate a slow Ca(2+)-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus ... ...

Abstract	NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A-D subunits that mediate a slow Ca(2+)-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus represent an important therapeutic target. We herein describe a novel series of pyrrolidinones that selectively potentiate only NMDA receptors that contain the GluN2C subunit. The most active analogues tested were over 100-fold selective for recombinant GluN2C-containing receptors over GluN2A/B/D-containing NMDA receptors as well as AMPA and kainate receptors. This series represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C-containing NMDA receptors.
MeSH term(s)	Animals ; Chromatography, High Pressure Liquid ; Computational Biology ; Drug Design ; Excitatory Amino Acid Agonists/chemical synthesis ; Excitatory Amino Acid Agonists/pharmacology ; High-Throughput Screening Assays ; Humans ; Indicators and Reagents ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Conformation ; Oocytes/drug effects ; Patch-Clamp Techniques ; Pyrrolidinones/chemical synthesis ; Pyrrolidinones/pharmacology ; Pyruvates/chemical synthesis ; Pyruvates/pharmacology ; Receptors, N-Methyl-D-Aspartate/agonists ; Stereoisomerism ; Structure-Activity Relationship ; Xenopus laevis
Chemical Substances	Excitatory Amino Acid Agonists ; Indicators and Reagents ; NR2C NMDA receptor ; Pyrrolidinones ; Pyruvates ; Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2014-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/jm401695d
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito