ArticleOpen access bioinformatics2010
Computational studies of NMDA receptors: differential effects of neuronal activity on efficacy of competitive and non-competitive antagonists.
Article in Open access bioinformatics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Neurosteroids, Microbiota, and Neuroinflammation: Mechanistic Insights and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- Experimentally Constrained Mechanistic and Data-Driven Models for Simulating NMDA Receptor Dynamics.Biomedicines · 2025Article
- Neurosteroids and neurological disorders.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Bridging Hierarchies in Multi-Scale Models of Neural Systems: Look-Up Tables Enable Computationally Efficient Simulations of Non-linear Synaptic Dynamics.Frontiers in computational neuroscience · 2021Article
- Article
- A Glutamatergic Spine Model to Enable Multi-Scale Modeling of Nonlinear Calcium Dynamics.Frontiers in computational neuroscience · 2018Article
- The Impact of Mathematical Modeling in Understanding the Mechanisms Underlying Neurodegeneration: Evolving Dimensions and Future Directions.CPT: pharmacometrics & systems pharmacology · 2017Review
- Volterra representation enables modeling of complex synaptic nonlinear dynamics in large-scale simulations.Frontiers in computational neuroscience · 2015Article
- Synaptic Efficacy as a Function of Ionotropic Receptor Distribution: A Computational Study.PloS one · 2015Article
- Integrating pathways of Parkinson's disease in a molecular interaction map.Molecular neurobiology · 2014Review
- A comparison between direct and indirect measurements of neurotransmitter vesicle release dynamics: a computational study.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2014Article
- Mechanistic systems modeling to guide drug discovery and development.Drug discovery today · 2013Review
- Insights on synaptic paired-pulse response using parametric and non-parametric models.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2013Article
- Influence of ionotropic receptors localization on glutamatergic synaptic response to paired-pulse stimulation protocol.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2013Article
- Modeling of the nervous system: from modulation of glutamatergic and gabaergic molecular dynamics to neuron spiking activity.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2012Article
- A computational model to investigate astrocytic glutamate uptake influence on synaptic transmission and neuronal spiking.Frontiers in computational neuroscience · 2012Article
- Integrated multiscale modeling of the nervous system: predicting changes in hippocampal network activity by a positive AMPA receptor modulator.IEEE transactions on bio-medical engineering · 2011Article
- Simulation of postsynaptic glutamate receptors reveals critical features of glutamatergic transmission.PloS one · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
N-Methyl-D-Aspartate receptors (NMDARs) play important physiological as well as pathological roles in the central nervous system (CNS). While NMDAR competitive antagonists, such as D-2-Amino-5-Phosphopentanoic acid (AP5) have been shown to impair learning and memory, the non-competitive antagonist, memantine, is paradoxically beneficial in mild to moderate Alzheimer's disease (AD) patients. It has been proposed that differences in kinetic properties could account for antagonist functional differences. Here we present a new elaborated kinetic model of NMDARs that incorporates binding sites for the agonist (glutamate) and co-agonist (glycine), channel blockers, such as memantine and magnesium (Mg(2+)), as well as competitive antagonists. We first validated and optimized the parameters used in the model by comparing simulated results with a wide range of experimental data from the literature. We then evaluated the effects of stimulation frequency and membrane potential (Vm) on the characteristics of AP5 and memantine inhibition of NMDARs. Our results indicated that the inhibitory effects of AP5 were independent of Vm but decreased with increasing stimulation frequency. In contrast, memantine inhibitory effects decreased with both increasing Vm and stimulation frequency. They support the idea that memantine could provide tonic blockade of NMDARs under basal stimulation conditions without blocking their activation during learning. Moreover they underline the necessity of considering receptor kinetics and the value of the biosimulation approach to better understand mechanisms of drug action and to identify new ways of regulating receptor function.
Identifiers
What OpenQuestion holds
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.