ArticlePloS one2016
The qEEG Signature of Selective NMDA NR2B Negative Allosteric Modulators; A Potential Translational Biomarker for Drug Development.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 22 citations in OpenAlex.
- High-order brain interactions in ketamine during rest and task: a double-blinded cross-over design using portable EEG on male participants.Translational psychiatry · 2024Trial
- MIJ821 (onfasprodil) in healthy volunteers: First-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose).Clinical and translational science · 2023Trial
- Targeting N-methyl-D-aspartate 2B receptor in painful diabetic neuropathy - mechanisms, challenges, and emerging therapeutics.World journal of diabetes · 2026Review
- High-order brain interactions in ketamine during rest and task: A double-blinded cross-over design using portable EEG.Research square · 2024Article
- Use of Quantitative Electroencephalography to Inform Age- and Sex-Related Differences in NMDA Receptor Function Following MK-801 Administration.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats.International journal of molecular sciences · 2021Article
- 4-MeO-PCP and 3-MeO-PCMo, new dissociative drugs, produce rewarding and reinforcing effects through activation of mesolimbic dopamine pathway and alteration of accumbal CREB, deltaFosB, and BDNF levels.Psychopharmacology · 2020Article
- Neurosteroid-sensitive δ-GABAEpilepsia · 2017Article
- NMDA Receptors in the Central Nervous System.Methods in molecular biology (Clifton, N.J.) · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antidepressant activity of the N-methyl-D-aspartate (NMDA) receptor channel blocker, ketamine, has led to the investigation of negative allosteric modulators (NAMs) selective for the NR2B receptor subtype. The clinical development of NR2B NAMs would benefit from a translational pharmacodynamic biomarker that demonstrates brain penetration and functional inhibition of NR2B receptors in preclinical species and humans. Quantitative electroencephalography (qEEG) is a translational measure that can be used to demonstrate pharmacodynamic effects across species. NMDA receptor channel blockers, such as ketamine and phencyclidine, increase the EEG gamma power band, which has been used as a pharmacodynamic biomarker in the development of NMDA receptor antagonists. However, detailed qEEG studies with ketamine or NR2B NAMs are lacking in nonhuman primates. The aim of the present study was to determine the effects on the qEEG power spectra of the NR2B NAMs traxoprodil (CP-101,606) and BMT-108908 in nonhuman primates, and to compare them to the NMDA receptor channel blockers, ketamine and lanicemine. Cynomolgus monkeys were surgically implanted with EEG radio-telemetry transmitters, and qEEG was measured after vehicle or drug administration. The relative power for a number of frequency bands was determined. Ketamine and lanicemine increased relative gamma power, whereas the NR2B NAMs traxoprodil and BMT-108908 had no effect. Robust decreases in beta power were elicited by ketamine, traxoprodil and BMT-108908; and these agents also produced decreases in alpha power and increases in delta power at the doses tested. These results suggest that measurement of power spectra in the beta and delta bands may represent a translational pharmacodynamic biomarker to demonstrate functional effects of NR2B NAMs. The results of these studies may help guide the selection of qEEG measures that can be incorporated into early clinical evaluation of NR2B NAMs in healthy humans.
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