PMID- 36890259
OWN - NLM
STAT- MEDLINE
DCOM- 20230831
LR  - 20230901
IS  - 1433-8491 (Electronic)
IS  - 0940-1334 (Print)
IS  - 0940-1334 (Linking)
VI  - 273
IP  - 7
DP  - 2023 Oct
TI  - Esmethadone-HCl (REL-1017): a promising rapid antidepressant.
PG  - 1463-1476
LID - 10.1007/s00406-023-01571-4 [doi]
AB  - This review article presents select recent studies that form the basis for the 
      development of esmethadone into a potential new drug. Esmethadone is a promising 
      member of the pharmacological class of uncompetitive N-methyl-D-aspartate 
      receptor (NMDAR) antagonists that have shown efficacy for major depressive 
      disorder (MDD) and other diseases and disorders, such as Alzheimer's dementia and 
      pseudobulbar affect. The other drugs in the novel class of NMDAR antagonists with 
      therapeutic uses that are discussed for comparative purposes in this review are 
      esketamine, ketamine, dextromethorphan, and memantine. We present in silico, in 
      vitro, in vivo, and clinical data for esmethadone and other uncompetitive NMDAR 
      antagonists that may advance our understanding of the role of these receptors in 
      neural plasticity in health and disease. The efficacy of NMDAR antagonists as 
      rapid antidepressants may advance our understanding of the neurobiology of MDD 
      and other neuropsychiatric diseases and disorders.
CI  - (c) 2023. The Author(s).
FAU - Fava, Maurizio
AU  - Fava M
AD  - Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 02114, USA.
FAU - Stahl, Stephen M
AU  - Stahl SM
AD  - Department of Psychiatry, VAMC (SD), University of California, San Diego, La 
      Jolla, CA, 92093, USA.
AD  - Neuroscience Education Institute, Carlsbad, CA, 92008, USA.
FAU - De Martin, Sara
AU  - De Martin S
AD  - Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 
      35122, Padua, Italy.
FAU - Mattarei, Andrea
AU  - Mattarei A
AD  - Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 
      35122, Padua, Italy.
FAU - Bettini, Ezio
AU  - Bettini E
AD  - In Vitro Pharmacology Department, Aptuit, an Evotec Company, 37135, Verona, 
      Italy.
FAU - Comai, Stefano
AU  - Comai S
AD  - Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 
      35122, Padua, Italy.
AD  - Department of Biomedical Sciences, University of Padua, 35122, Padua, Italy.
AD  - Department of Psychiatry, McGill University, Montreal, QC, H3A 1A1, Canada.
FAU - Alimonti, Andrea
AU  - Alimonti A
AD  - Department of Health Sciences and Technology, ETH Zurich, 8092, Zurich, 
      Switzerland.
AD  - Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland 
      (IOSI), 6500, Bellinzona, Switzerland.
AD  - Universita della Svizzera Italiana, 6900, Lugano, Switzerland.
AD  - Veneto Institute of Molecular Medicine, 35129, Padua, Italy.
AD  - Department of Medicine-DIMED, University of Padua, 35122, Padua, Italy.
FAU - Bifari, Francesco
AU  - Bifari F
AD  - Department of Medical Biotechnology and Translational Medicine, University of 
      Milan, 20122, Milan, Italy.
FAU - Pani, Luca
AU  - Pani L
AD  - Relmada Therapeutics, Coral Gables, FL, 33134, USA.
AD  - Department of Psychiatry and Behavioral Sciences, School of Medicine, University 
      of Miami, Miami, FL, 33146, USA.
AD  - Department of Biomedical, Metabolic and Neural Sciences, University of Modena and 
      Reggio Emilia, 41121, Modena, Italy.
FAU - Folli, Franco
AU  - Folli F
AD  - Department of Health Sciences, University of Milan, 20122, Milan, Italy.
FAU - Guidetti, Clotilde
AU  - Guidetti C
AD  - Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino 
      Gesu Pediatric Hospital, 00165, Rome, Italy.
FAU - Furlan, Alberto
AU  - Furlan A
AD  - Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 
      35122, Padua, Italy.
FAU - Sgrignani, Jacopo
AU  - Sgrignani J
AD  - Institute for Research in Biomedicine (IRB), Universita della Svizzera Italiana 
      (USI), 6500, Bellinzona, Switzerland.
FAU - Locatelli, Patrizia
AU  - Locatelli P
AD  - Institute for Research in Biomedicine (IRB), Universita della Svizzera Italiana 
      (USI), 6500, Bellinzona, Switzerland.
FAU - Cavalli, Andrea
AU  - Cavalli A
AD  - Institute for Research in Biomedicine (IRB), Universita della Svizzera Italiana 
      (USI), 6500, Bellinzona, Switzerland.
AD  - Swiss Institute of Bioinformatics, 1015, Lausanne, Switzerland.
FAU - O'Gorman, Cedric
AU  - O'Gorman C
AD  - Relmada Therapeutics, Coral Gables, FL, 33134, USA.
FAU - Traversa, Sergio
AU  - Traversa S
AD  - Relmada Therapeutics, Coral Gables, FL, 33134, USA.
FAU - Inturrisi, Charles E
AU  - Inturrisi CE
AD  - Relmada Therapeutics, Coral Gables, FL, 33134, USA.
FAU - Pappagallo, Marco
AU  - Pappagallo M
AD  - Relmada Therapeutics, Coral Gables, FL, 33134, USA.
FAU - Manfredi, Paolo L
AU  - Manfredi PL
AD  - Relmada Therapeutics, Coral Gables, FL, 33134, USA. pmanfredi@relmada.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230308
PL  - Germany
TA  - Eur Arch Psychiatry Clin Neurosci
JT  - European archives of psychiatry and clinical neuroscience
JID - 9103030
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - W8O17SJF3T (Memantine)
RN  - 0 (Antidepressive Agents)
SB  - IM
MH  - Humans
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - *Depressive Disorder, Major/drug therapy
MH  - Memantine/pharmacology/therapeutic use
MH  - Antidepressive Agents/pharmacology/therapeutic use
MH  - *Alzheimer Disease/drug therapy
PMC - PMC10465385
OTO - NOTNLM
OT  - Esketamine
OT  - Esmethadone
OT  - Ketamine
OT  - Major depressive disorder
OT  - N-Methyl-D-aspartate receptor
OT  - REL-1017
COIS- Relmada Therapeutics and its consultants and employees contributed to all aspects 
      of this manuscript, including all described experimental work. 
EDAT- 2023/03/09 06:00
MHDA- 2023/08/31 06:41
PMCR- 2023/03/08
CRDT- 2023/03/08 23:19
PHST- 2022/11/28 00:00 [received]
PHST- 2023/02/13 00:00 [accepted]
PHST- 2023/08/31 06:41 [medline]
PHST- 2023/03/09 06:00 [pubmed]
PHST- 2023/03/08 23:19 [entrez]
PHST- 2023/03/08 00:00 [pmc-release]
AID - 10.1007/s00406-023-01571-4 [pii]
AID - 1571 [pii]
AID - 10.1007/s00406-023-01571-4 [doi]
PST - ppublish
SO  - Eur Arch Psychiatry Clin Neurosci. 2023 Oct;273(7):1463-1476. doi: 
      10.1007/s00406-023-01571-4. Epub 2023 Mar 8.