The N-methyl-d-aspartate receptor hypothesis of ketamine's antidepressant action: evidence and controversies.
Philos Trans R Soc Lond B Biol Sci
; 379(1906): 20230225, 2024 Jul 29.
Article
en En
| MEDLINE
| ID: mdl-38853549
ABSTRACT
Substantial clinical evidence has unravelled the superior antidepressant efficacy of ketamine in comparison to traditional antidepressants targeting the monoamine systems, ketamine, as an N-methyl-d-aspartate receptor (NMDAR) antagonist, acts much faster and more potently. Surrounding the antidepressant mechanisms of ketamine, there is ample evidence supporting an NMDAR-antagonism-based hypothesis. However, alternative arguments also exist, mostly derived from the controversial clinical results of other NMDAR inhibitors. In this article, we first summarize the historical development of the NMDAR-centred hypothesis of rapid antidepressants. We then classify different NMDAR inhibitors based on their mechanisms of inhibition and evaluate preclinical as well as clinical evidence of their antidepressant effects. Finally, we critically analyse controversies and arguments surrounding ketamine's NMDAR-dependent and NMDAR-independent antidepressant action. A better understanding of ketamine's molecular targets and antidepressant mechanisms should shed light on the future development of better treatment for depression. This article is part of a discussion meeting issue 'Long-term potentiation 50 years on'.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de N-Metil-D-Aspartato
/
Ketamina
/
Antidepresivos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Philos Trans R Soc Lond B Biol Sci
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido