The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate
Open accessAbstract
The interaction of two dissociative anaesthetics, ketamine and phencyclidine, with the responses of spinal neurones to the electrophoretic administration of amino acids and acetylcholine was studied in decerebrate or pentobarbitone‐anaesthetized cats and rats. Both ketamine and phencyclidine selectively blocked excitation by N‐methyl‐aspartate (NMA) with little effect on excitation by quisqualate and kainate. Ketamine reduced responses to L‐aspartate somewhat more than those of l‐glutamate; the sensitivity of responses to these two putative transmitters was between that to NMA on one hand and that to quisqualate or kainate on the other. On Renshaw cells, ketamine and phencyclidine reduced responses to acetylcholine less than those to NMA but more than those to quisqualate or kainate. Dorsal root‐evoked synaptic excitation of Renshaw cells was reduced to a greater extent than that following ventral root excitation. Intravenous ketamine, 2.5–20 mg/kg, and phencyclidine, 0.2–0.5 mg/kg, also selectively blocked excitation of neurones by NMA. Ketamine showed no consistent or selective effect on inhibition of spinal neurones by electrophoretically administered glycine or γ‐aminobutyricacid (GABA). The results suggest that reduction of synaptic excitation mediated via NMA receptors contributes to the anaesthetic/analgesic properties of these two dissociative anaesthetics.
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Ketamine was first characterized as an NMDAR antagonist.
“Ketamine was initially characterized as an NMDAR antagonist”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Anis et al., 1983
NMDA receptor antagonists such as ketamine and 5-HT2A receptor agonists such as serotonergic psychedelics produce rapid and sometimes robust antidepressant effects.
“Recent studies have shown that NMDA receptor antagonists like ketamine and 5-HT2A receptor agonists like serotonergic psychedelics (the most studied include lysergic acid diethylamide/LSD and psilocybin) induce rapid and sometimes robust antidepressant effects190-193.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [193]
The hypothesis that NMDAR hypofunction might be a pathogenic trigger for schizophrenia arose from observations that phencyclidine and ketamine mimic primary schizophrenia symptoms in healthy subjects and are NMDAR antagonists.
“The hypothesis that NMDAR hypofunction might be a pathogenic trigger for schizophrenia 9,10 arose from observations that administration of the dissociative anesthetics phencyclidine and ketamine to healthy subjects mimicked the primary symptoms of schizophrenia 11,12 coupled with the finding that these compounds are NMDAR antagonists 13 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [13]
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- Authors
- Anis, N. A., Berry, S. C., Burton, N. R., & Lodge, D.
- Affiliations
- Royal Veterinary College (GB)
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1983-06
- Volume
- 79
- Issue
- 2
- Pages
- 565-575
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2044888
- OpenAlex
- W2170029299
- Cited by
- 1,399
- References
- 54
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 33 · 2023: 35 · 2022: 30 · 2021: 35 · 2020: 42 · 2019: 23 · 2018: 35 · 2017: 40 · 2016: 37 · 2015: 22 · 2014: 19 · 2013: 25 · 2012: 33
- FWCI
- 8.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- ketamine, phencyclidine, dissociative anesthetics, synaptic excitation, Renshaw cells, quisqualate, kainic acid, L-aspartic acid, glutamate, acetylcholine, glycine, GABA
- MeSH terms
- Acetylcholine, Animals, Aspartic Acid, Cats, Female, Ketamine, Male, Neurons, Phencyclidine, Receptors, Cell Surface, Spinal Cord, Synapses, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Rats, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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