ArticleBritish journal of pharmacology2015
Interaction between positive allosteric modulators and trapping blockers of the NMDA receptor channel.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Memantine: updates from the past decade and implications for future novel therapeutic applications.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Role of cholesterol in modulating brain hyperexcitability.Epilepsia · 2025Review
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- Targeting cytochrome P450 46A1 and brain cholesterol 24-hydroxylation to treat neurodegenerative diseases.Exploration of neuroprotective therapy · 2021Article
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- Cholesterol metabolism and brain injury in neonatal encephalopathy.Pediatric research · 2021Review
- The Controversial Role of 24-S-Hydroxycholesterol in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2021Review
- A neuroactive steroid with a therapeutically interesting constellation of actions at GABANeuropharmacology · 2021Article
- Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications.Frontiers in aging neuroscience · 2021Review
- Preferential enhancement of GluN2B-containing native NMDA receptors by the endogenous modulator 24S-hydroxycholesterol in hippocampal neurons.Neuropharmacology · 2019Article
- Enhanced GABAergic actions resulting from the coapplication of the steroid 3α-hydroxy-5α-pregnane-11,20-dione (alfaxalone) with propofol or diazepam.Scientific reports · 2018Article
- Positive Allosteric Modulation as a Potential Therapeutic Strategy in Anti-NMDA Receptor Encephalitis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- A Clickable Oxysterol Photolabel Retains NMDA Receptor Activity and Accumulates in Neurons.Frontiers in neuroscience · 2018Article
- Article
- The Role of GluN2C-Containing NMDA Receptors in Ketamine's Psychotogenic Action and in Schizophrenia Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Ketamine: NMDA Receptors and Beyond.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- 24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2016Review
- Comparison of Steroid Modulation of Spontaneous Inhibitory Postsynaptic Currents in Cultured Hippocampal Neurons and Steady-State Single-Channel Currents from Heterologously Expressed α1β2γ2L GABA(A) Receptors.Molecular pharmacology · 2016Article
- Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices.Journal of neurophysiology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
background and purposeMemantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how positive allosteric modulators (PAMs) might affect the pharmacodynamics of these NMDA blockers. EXPERIMENTAL APPROACH: We used two different PAMs: SGE-201, an analogue of an endogenous oxysterol, 24S-hydroxycholesterol, along with pregnenolone sulphate (PS), to test on memantine and ketamine responses in single cells (oocytes and cultured neurons) and networks (hippocampal slices), using standard electrophysiological techniques. KEY
resultsSGE-201 and PS had no effect on steady-state block or voltage dependence of a channel blocker. However, both PAMs increased the actions of memantine and ketamine on phasic excitatory post-synaptic currents, but neither revealed underlying pharmacodynamic differences. SGE-201 accelerated the re-equilibration of blockers during voltage jumps. SGE-201 also unmasked differences among the blockers in neuronal networks - measured either by suppression of activity in multi-electrode arrays or by neuroprotection against a mild excitotoxic insult. Either potentiating NMDA receptors while maintaining the basal activity level or increasing activity/depolarization without potentiating NMDA receptor function is sufficient to expose pharmacodynamic blocker differences in suppressing network function and in neuroprotection. CONCLUSIONS AND IMPLICATIONS: Positive modulation revealed no pharmacodynamic differences between NMDA receptor blockers at a constant voltage, but did expose differences during spontaneous network activity. Endogenous modulator tone of NMDA receptors in different brain regions may underlie differences in the effects of NMDA receptor blockers on behaviour.
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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.