PMID- 35182519
OWN - NLM
STAT- MEDLINE
DCOM- 20220425
LR  - 20220425
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 198
DP  - 2022 Apr
TI  - Is (R)-ketamine a potential therapeutic agent for treatment-resistant depression 
      with less detrimental side effects? A review of molecular mechanisms underlying 
      ketamine and its enantiomers.
PG  - 114963
LID - S0006-2952(22)00057-0 [pii]
LID - 10.1016/j.bcp.2022.114963 [doi]
AB  - Approximately one-third of individuals with major depressive disorder are 
      resistant to conventional antidepressants (i.e., monoamine-based therapies), and, 
      even among respondents, a proper therapeutic effect may require weeks of 
      treatment. Ketamine, a racemic mixture of the two enantiomers, (R)-ketamine and 
      (S)-ketamine, is an N-methyl-d-aspartate receptor (NMDAR) antagonist and has been 
      shown to have rapid-acting antidepressant properties in patients with 
      treatment-resistant depression (TRD). Although (R)-ketamine has a lower affinity 
      for NMDAR, it presents greater potency and longer-lasting antidepressant 
      properties, with no major side effects, than racemic ketamine or (S)-ketamine in 
      preclinical findings. Thereby, ketamine and its enantiomers have not only an 
      antagonistic effect on NMDAR but also a strong synaptogenic-modulatory effect, 
      which is impaired in TRD pathophysiology. In this review, we summarize the 
      current evidence regarding the modulation of neurotransmission, neuroplasticity, 
      and neural network activity as putative mechanisms of these rapid-acting 
      antidepressants, highlighting differences on intracellular signaling pathways of 
      synaptic proteins such as mammalian target of rapamycin (mTOR), extracellular 
      signal-regulated kinase (ERK) and brain-derived neurotrophic factor (BDNF). In 
      addition, we discuss probable mechanisms involved in the side effects of ketamine 
      and its enantiomers.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Scotton, Ellen
AU  - Scotton E
AD  - Laboratorio de Psiquiatria Molecular, Hospital de Clinicas de Porto Alegre, Porto 
      Alegre, RS, Brazil; Department of Pharmacology, Programa de Pos-Graduacao em 
      Farmacologia e Terapeutica, UFRGS, Porto Alegre, RS, Brazil.
FAU - Antqueviezc, Barbara
AU  - Antqueviezc B
AD  - Laboratorio de Psiquiatria Molecular, Hospital de Clinicas de Porto Alegre, Porto 
      Alegre, RS, Brazil.
FAU - Vasconcelos, Mailton Franca de
AU  - Vasconcelos MF
AD  - Laboratorio de Psiquiatria Molecular, Hospital de Clinicas de Porto Alegre, Porto 
      Alegre, RS, Brazil; Instituto de Psicologia, Universidade Federal do Rio Grande 
      do Sul (UFRGS), Porto Alegre, RS, Brazil.
FAU - Dalpiaz, Giovana
AU  - Dalpiaz G
AD  - Laboratorio de Psiquiatria Molecular, Hospital de Clinicas de Porto Alegre, Porto 
      Alegre, RS, Brazil.
FAU - Paul Gea, Luiza
AU  - Paul Gea L
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, ON, Canada.
FAU - Ferraz Goularte, Jeferson
AU  - Ferraz Goularte J
AD  - Laboratorio de Psiquiatria Molecular, Hospital de Clinicas de Porto Alegre, Porto 
      Alegre, RS, Brazil; Programa de Pos-Graduacao em Psiquiatria e Ciencias do 
      Comportamento, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 
      RS, Brazil. Electronic address: jefgoularte@hcpa.edu.br.
FAU - Colombo, Rafael
AU  - Colombo R
AD  - Laboratorio de Psiquiatria Molecular, Hospital de Clinicas de Porto Alegre, Porto 
      Alegre, RS, Brazil; Programa de Pos-Graduacao em Biotecnologia, Universidade de 
      Caxias do Sul (UCS), Caxias do Sul, RS, Brazil; Programa de Pos-Graduacao em 
      Ciencias da Saude, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, 
      Brazil. Electronic address: rcolombo1@ucs.br.
FAU - Ribeiro Rosa, Adriane
AU  - Ribeiro Rosa A
AD  - Laboratorio de Psiquiatria Molecular, Hospital de Clinicas de Porto Alegre, Porto 
      Alegre, RS, Brazil; Department of Pharmacology, Programa de Pos-Graduacao em 
      Farmacologia e Terapeutica, UFRGS, Porto Alegre, RS, Brazil; Programa de 
      Pos-Graduacao em Psiquiatria e Ciencias do Comportamento, Universidade Federal do 
      Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: 
      arrosa@hcpa.edu.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220216
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antidepressive Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Antidepressive Agents/adverse effects
MH  - Depression/metabolism
MH  - *Depressive Disorder, Major/drug therapy
MH  - Humans
MH  - *Ketamine/adverse effects
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
OTO - NOTNLM
OT  - (R)-ketamine
OT  - (S)-ketamine
OT  - Ketamine enantiomers
OT  - Neuroplasticity
OT  - Racemic ketamine
OT  - Treatment resistant depression
EDAT- 2022/02/20 06:00
MHDA- 2022/04/26 06:00
CRDT- 2022/02/19 20:09
PHST- 2021/12/14 00:00 [received]
PHST- 2022/02/09 00:00 [revised]
PHST- 2022/02/10 00:00 [accepted]
PHST- 2022/02/20 06:00 [pubmed]
PHST- 2022/04/26 06:00 [medline]
PHST- 2022/02/19 20:09 [entrez]
AID - S0006-2952(22)00057-0 [pii]
AID - 10.1016/j.bcp.2022.114963 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2022 Apr;198:114963. doi: 10.1016/j.bcp.2022.114963. Epub 2022 
      Feb 16.