Ketamine's dose related multiple mechanisms of actions: Dissociative anesthetic to rapid antidepressant.


Journal

Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872

Informations de publication

Date de publication:
15 07 2020
Historique:
received: 24 11 2019
revised: 19 03 2020
accepted: 29 03 2020
pubmed: 22 5 2020
medline: 26 10 2021
entrez: 22 5 2020
Statut: ppublish

Résumé

Ketamine induces safe and effective anesthesia and displays unusual cataleptic properties that gave rise to the term dissociative anesthesia. Since 1970, clinicians only utilized the drug as an anesthetic or analgesic for decades, but ketamine was found to have rapid acting antidepressant effects in 1990s. Accumulated evidence exhibits NMDAR antagonism may not be the only mechanism of ketamine. The contributions of AMPA receptor, mTor signal pathway, monoaminergic system, sigma-1 receptor, cholinergic, opioid and cannabinoid systems, as well as voltage-gated calcium channels and hyperpolarization cyclic nucleotide gated channels are discussed for the antidepressant effects. Also the effects of ketamine's enantiomers and metabolites are reviewed. Furthermore ketamine's anesthetic and analgesic mechanisms are briefly revisited. Overall, pharmacology of ketamine, its enantiomers and metabolites is very unique. Insight into multiple mechanisms of action will provide further development and desirable clinical effects of ketamine.

Identifiants

pubmed: 32437885
pii: S0166-4328(20)30330-2
doi: 10.1016/j.bbr.2020.112631
pii:
doi:

Substances chimiques

Anesthetics, Dissociative 0
Antidepressive Agents 0
Receptors, Neurotransmitter 0
Ketamine 690G0D6V8H

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

112631

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Eli Lavender (E)

University of Michigan Medical School, Department of Pharmacology, 1150 W Medical Center Dr, Ann Arbor, MI 48109, USA.

Mika Hirasawa-Fujita (M)

University of Michigan Medical School, Department of Pharmacology, 1150 W Medical Center Dr, Ann Arbor, MI 48109, USA.

Edward F Domino (EF)

University of Michigan Medical School, Department of Pharmacology, 1150 W Medical Center Dr, Ann Arbor, MI 48109, USA. Electronic address: efdabcde@umich.edu.

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Classifications MeSH