ArticleACS chemical neuroscience2011
Mechanism of Inhibition of the GluA2 AMPA Receptor Channel Opening: the Role of 4-Methyl versus 4-Carbonyl Group on the Diazepine Ring of 2,3-Benzodiazepine Derivatives.
Article in ACS chemical neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Allosteric competition and inhibition in AMPA receptors.Nature structural & molecular biology · 2024Article
- Allosteric Competition and Inhibition in AMPA Receptors.bioRxiv : the preprint server for biology · 2023Article
- Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design, synthesis, anticonvulsant evaluation, ADMET profile and molecular docking.Molecular diversity · 2019Article
- Noncompetitive antagonists induce cooperative AMPA receptor channel gating.The Journal of general physiology · 2019Article
- Identification and characterization of RNA aptamers: A long aptamer blocks the AMPA receptor and a short aptamer blocks both AMPA and kainate receptors.The Journal of biological chemistry · 2017Article
- Structural Bases of Noncompetitive Inhibition of AMPA-Subtype Ionotropic Glutamate Receptors by Antiepileptic Drugs.Neuron · 2016Article
- Mechanism-based design of 2,3-benzodiazepine inhibitors for AMPA receptors.Acta pharmaceutica Sinica. B · 2015Review
- Mechanism of inhibition of the GluA1 AMPA receptor channel opening by the 2,3-benzodiazepine compound GYKI 52466 and a N-methyl-carbamoyl derivative.Biochemistry · 2014Article
- Mechanism and site of inhibition of AMPA receptors: pairing a thiadiazole with a 2,3-benzodiazepine scaffold.ACS chemical neuroscience · 2014Article
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- Mechanism of inhibition of the GluA2 AMPA receptor channel opening by talampanel and its enantiomer: the stereochemistry of the 4-methyl group on the diazepine ring of 2,3-benzodiazepine derivatives.ACS chemical neuroscience · 2013Article
- AMPA receptors as a molecular target in epilepsy therapy.Acta neurologica Scandinavica. Supplementum · 2013Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
2,3-Benzodiazepine derivatives are synthesized as drug candidates for a potential treatment of various neurodegenerative diseases involving the excessive activity of AMPA receptors. Here, we describe a rapid kinetic investigation of the mechanism of inhibition of the GluA2Q(flip) AMPA receptor channel opening by two 2,3-benzodiazepine derivatives, i.e. the prototypic 2,3-benzodiazepine compound GYKI 52466 [(1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine)] and 1-(4-aminophenyl)-3,5-dihydro-7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one (BDZ-2). GYKI 52466 and BDZ-2 are structurally similar in that the 4-methyl group in the diazepine ring of GYKI 52466 is replaced by a carbonyl group, yielding BDZ-2. Using a laser-pulse photolysis technique with ∼60 μs time resolution, we characterize the effect of the two compounds individually on the channel-opening process of the GluA2Q(flip) receptor expressed in HEK-293 cells. We find that BDZ-2 preferentially inhibits the open-channel state, whereas GYKI 52466 is more selective for the closed-channel state of the GluA2Q(flip) receptors. Each inhibitor binds independently to its own noncompetitive site, yet the two sites do not interact allosterically. The significance of these results in the context of both the structure-activity relationship and the properties of the GluA2Q(flip) receptor channels is presented.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.