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Cited by 711Anesthesia and Neurotoxicity ResearchAnesthesia and Sedative AgentsAnesthesia and Pain Management

Ketamine Pharmacology: An Update ( Pharmacodynamics and Molecular Aspects, Recent Findings )

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Mion, Georges, Villevieille, Thierry·2013·CNS Neuroscience & Therapeutics
DOI 10.1111/cns.12099PMC PMC6493357
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Abstract

Summary: For more than 50 years, ketamine has proven to be a safe anesthetic drug with potent analgesic properties. The active enantiomer is S (+)‐ketamine. Ketamine is mostly metabolized in norketamine, an active metabolite. During “dissociative anesthesia”, sensory inputs may reach cortical receiving areas, but fail to be perceived in some association areas. Ketamine also enhances the descending inhibiting serotoninergic pathway and exerts antidepressive effects. Analgesic effects persist for plasma concentrations ten times lower than hypnotic concentrations. Activation of the (N‐Methyl‐D‐Aspartate [NMDA]) receptor plays a fundamental role in long‐term potentiation but also in hyperalgesia and opioid‐induced hyperalgesia. The antagonism of NMDA receptor is responsible for ketamine's more specific properties. Ketamine decreases the “wind up” phenomenon, and the antagonism is more important if the NMDA channel has been previously opened by the glutamate binding (“use dependence”). Experimentally, ketamine may promote neuronal apoptotic lesions but, in usual clinical practice, it does not induce neurotoxicity. The consequences of high doses, repeatedly administered, are not known. Cognitive disturbances are frequent in chronic users of ketamine, as well as frontal white matter abnormalities. Animal studies suggest that neurodegeneration is a potential long‐term risk of anesthetics in neonatal and young pediatric patients.

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Authors
Mion, G., & Villevieille, T.
Affiliations
  • Hôpital Cochin (FR)
  • Hôpital d'Instruction des Armées Bégin (FR)
Corresponding author
Mion, Georges
ORCID
Mion, Georges
Venue
CNS Neuroscience & Therapeutics
Publisher
Wiley
Published
2013-04-10
Volume
19
Issue
6
Pages
370-380
ISSN
  • 1755-5930 (ISSN-L)
  • 1755-5949
DOI
10.1111/cns.12099
PMC
PMC6493357
OpenAlex
W2108466731
Cited by
711
References
6
Citations by year
2026: 68 · 2025: 88 · 2024: 66 · 2023: 71 · 2022: 61 · 2021: 56 · 2020: 86 · 2019: 39 · 2018: 50 · 2017: 39 · 2016: 38 · 2015: 21 · 2014: 23 · 2013: 5
FWCI
10.75
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • CNS Neuroscience & Therapeutics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
  • Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
Keywords
ketamine, pharmacodynamics, dissociative anesthesia, analgesia, norketamine, NMDA receptor antagonism, long-term potentiation, hyperalgesia, opioid-induced hyperalgesia, antidepressant effects, neurotoxicity, neuronal apoptosis, cognitive disorders, pediatric anesthesia
MeSH terms
Anesthetics, Animals, Cognition, Dose-Response Relationship, Drug, Humans, Ketamine, Receptors, N-Methyl-D-Aspartate, History, 20th Century, History, 21st Century

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