R (-)-methoxetamine exerts rapid and sustained antidepressant effects and fewer behavioral side effects relative to S (+)-methoxetamine.

Animals Antidepressive Agents / adverse effects Brain-Derived Neurotrophic Factor / metabolism Cyclohexanones / adverse effects Cyclohexylamines / adverse effects Depression / drug therapy Elevated Plus Maze Test HEK293 Cells Hindlimb Suspension Humans Ketamine Male Mice Mice, Inbred C57BL Motor Activity / drug effects Receptors, AMPA / metabolism Receptors, Serotonin / metabolism mTOR Associated Protein, LST8 Homolog / metabolism
Antidepressant Depression Enantiomers Methoxetamine NMDA receptor Antagonist

Journal

Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217

Informations de publication

Date de publication:
01 08 2021
Historique:
received: 13 01 2021
revised: 03 05 2021
accepted: 15 05 2021
pubmed: 24 5 2021
medline: 22 12 2021
entrez: 23 5 2021
Statut: ppublish

Résumé

The newfound antidepressant efficacy of ketamine has provided opportunities for the development of new-generation, rapid-acting, glutamate-based antidepressants. We previously identified that methoxetamine (MXE), a ketamine analog, and an N-Methyl-d-aspartate (NMDA) receptor antagonist, produced rapid and sustained antidepressant effects in mice. MXE (R, S (±)-MXE) is a racemic mixture containing equal parts of S (+)-MXE and R (-)-MXE. However, studies have yet to investigate the antidepressant effects of its enantiomers. Here, we examined the potential antidepressant properties and behavioral side effects of S- and R-MXE in mice. Both S- and R-MXE showed significant NMDA receptor affinity and appreciable inhibitory activity on serotonin transporter. Also, S- and R-MXE (10 mg kg

Identifiants

DOI: 10.1016/j.neuropharm.2021.108619 PMID: 34023336
pubmed: 34023336
pii: S0028-3908(21)00173-8
doi: 10.1016/j.neuropharm.2021.108619
pii:
doi:

Substances chimiques

Antidepressive Agents 0
Brain-Derived Neurotrophic Factor 0
Cyclohexanones 0
Cyclohexylamines 0
Receptors, AMPA 0
Receptors, Serotonin 0
mTOR Associated Protein, LST8 Homolog 0
Ketamine 690G0D6V8H
2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone ZO5ZCE6E12

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

108619

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Chrislean Jun Botanas (CJ)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea.

Raly James Perez Custodio (RJ)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea.

Hee Jin Kim (HJ)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea.

June Bryan de la Pena (JB)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea; Department of Biological Sciences, University of Texas Dallas, Richardson, TX, 75080, United States.

Leandro Val Sayson (LV)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea.

Darlene Mae Ortiz (DM)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea.

Mikyung Kim (M)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea; Department of Chemistry and Life Science, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea.

Hyun Jun Lee (HJ)

Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul, 01795, Republic of Korea.

Srijan Acharya (S)

Department of Pharmacology, College of Pharmacy, Chonnam National University, Gwangju, 61186, Republic of Korea.

Kyeong-Man Kim (KM)

Department of Pharmacology, College of Pharmacy, Chonnam National University, Gwangju, 61186, Republic of Korea.

Cheol Jung Lee (CJ)

Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea.

Jong Hoon Ryu (JH)

Department of Life and Nanopharmaceutical Science, Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea.

Yong Sup Lee (YS)

Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea. Electronic address: kyslee@khu.ac.kr.

Jae Hoon Cheong (JH)

School of Pharmacy, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do, 54896 Republic of Korea. Electronic address: cheongjh@jbnu.ac.kr.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Psychoanaleptiques › Antidépresseurs › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance nerveuse › Facteur neurotrophique dérivé du cerveau › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Composés chimiques organiques › Cétones › Cyclohexanones › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures alicycliques › Cyclohexanes › Cyclohexylamines › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Émotions › Dépression › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Apprentissage du labyrinthe › Test du labyrinthe en croix surélevé › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Environnement et santé publique › Environnement › Environnement contrôlé › Simulation d'environnement spatial › Simulation d'apesanteur › Suspension des membres postérieurs › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures alicycliques › Cyclohexanes › Kétamine › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Mouvement › Activité motrice › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs aux acides aminés › Récepteurs au glutamate › Récepteurs ionotropes du glutamate › Récepteur de l'AMPA › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs sérotoninergiques › R (-)-methoxetamine exerts rapid and sustained...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Complexe-1 cible mécanistique de la rapamycine › Protéine homologue de LST8 associée à MTOR › R (-)-methoxetamine exerts rapid and sustained...