Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling.

N-methyl-D-aspartate receptor REL-1017 d-methadone depression dextromethorphan esketamine esmethadone ketamine major depressive disorder neural plasticity

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
13 Oct 2022
Historique:
received: 31 08 2022
revised: 04 10 2022
accepted: 10 10 2022
entrez: 27 10 2022
pubmed: 28 10 2022
medline: 29 10 2022
Statut: epublish

Résumé

This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in animal models of depressive-like behavior and in patients with MDD via preferential tonic block of pathologically hyperactive GluN2D subtypes. Tonic Ca

Identifiants

pubmed: 36293063
pii: ijms232012196
doi: 10.3390/ijms232012196
pmc: PMC9602945
pii:
doi:

Substances chimiques

Receptors, N-Methyl-D-Aspartate 0
Antidepressive Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Relmada Therapeutics
ID : VDD9974

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Auteurs

Stephen M Stahl (SM)

Department of Psychiatry, VAMC (SD), University of California, La Jolla, San Diego, CA 92093, USA.
Neuroscience Education Institute, Carlsbad, CA 92008, USA.

Sara De Martin (S)

Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35122 Padua, Italy.

Andrea Mattarei (A)

Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35122 Padua, Italy.

Ezio Bettini (E)

In Vitro Pharmacology Department, Aptuit, An Evotec Company, 37135 Verona, Italy.

Luca Pani (L)

Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Miami, Miami, FL 33146, USA.
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41121 Modena, Italy.
Relmada Therapeutics, Coral Gables, FL 33134, USA.

Clotilde Guidetti (C)

Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Pediatric Hospital, 00165 Rome, Italy.

Franco Folli (F)

Department of Health Sciences, University of Milan, 20122 Milan, Italy.

Marc de Somer (M)

Relmada Therapeutics, Coral Gables, FL 33134, USA.

Sergio Traversa (S)

Relmada Therapeutics, Coral Gables, FL 33134, USA.

Charles E Inturrisi (CE)

Relmada Therapeutics, Coral Gables, FL 33134, USA.

Marco Pappagallo (M)

Relmada Therapeutics, Coral Gables, FL 33134, USA.

Marco Gentilucci (M)

MGGM LLC, 85 Baker Road, Kerhonkson, NY 12446, USA.

Andrea Alimonti (A)

Institute of Oncology Research, Southern Switzerland, 6500 Bellinzona, Switzerland.
The Institute of Oncology Research, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
Veneto Institute of Molecular Medicine, 35129 Padua, Italy.
Department of Medicine, Zurich University, 8006 Zurich, Switzerland.
Department of Medicine-DIMED, University of Padua, 35122 Padua, Italy.

Maurizio Fava (M)

Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.

Paolo L Manfredi (PL)

Relmada Therapeutics, Coral Gables, FL 33134, USA.

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Classifications MeSH