The antidepressant potential of (2R,6R)-hydroxynorketamine: A detailed review of pre-clinical findings

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F25%3A43921532" target="_blank" >RIV/00023752:_____/25:43921532 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/25:43928355

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0014299925003589?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0014299925003589?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2025.177604" target="_blank" >10.1016/j.ejphar.2025.177604</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The antidepressant potential of (2R,6R)-hydroxynorketamine: A detailed review of pre-clinical findings

Popis výsledku v původním jazyce

Depression affects hundreds of millions globally, and in 2019, esketamine, an S-enantiomer of ketamine, was approved for treatment-resistant depression (TRD). While effective, esketamine carries risks, including abuse potential and adverse effects even at low doses. As a result, ketamine&apos;s metabolite, (2R,6R)-hydroxynorketamine ((2R,6R)-HNK), has garnered attention for its potential antidepressant effects without these drawbacks.This selective review evaluates preclinical behavioral evidence for (2R,6R)-HNK&apos;s antidepressant properties, focusing on rodent studies that used established depression models. Results showed that (2R,6R)-HNK reduced behavioral despair, anhedonia, anxiety, and social avoidance in both stressed and non-stressed rodents. Antidepressant effects were observed at doses between 5 and 125 mg/kg, with rapid onset (30 min) and long-lasting effects (up to 21 days). However, some studies failed to demonstrate significant antidepressant effects at doses below 40 mg/kg, often in models with pre-induced depression. No significant adverse effects were reported, but data on side effects were limited.In conclusion, (2R,6R)-HNK shows promise as a next-generation antidepressant. However, further research is needed to fully understand its long-term safety and mechanisms, and to determine its advantages over existing treatments like esketamine, particularly for TRD patients.

Název v anglickém jazyce

The antidepressant potential of (2R,6R)-hydroxynorketamine: A detailed review of pre-clinical findings

Popis výsledku anglicky

Depression affects hundreds of millions globally, and in 2019, esketamine, an S-enantiomer of ketamine, was approved for treatment-resistant depression (TRD). While effective, esketamine carries risks, including abuse potential and adverse effects even at low doses. As a result, ketamine&apos;s metabolite, (2R,6R)-hydroxynorketamine ((2R,6R)-HNK), has garnered attention for its potential antidepressant effects without these drawbacks.This selective review evaluates preclinical behavioral evidence for (2R,6R)-HNK&apos;s antidepressant properties, focusing on rodent studies that used established depression models. Results showed that (2R,6R)-HNK reduced behavioral despair, anhedonia, anxiety, and social avoidance in both stressed and non-stressed rodents. Antidepressant effects were observed at doses between 5 and 125 mg/kg, with rapid onset (30 min) and long-lasting effects (up to 21 days). However, some studies failed to demonstrate significant antidepressant effects at doses below 40 mg/kg, often in models with pre-induced depression. No significant adverse effects were reported, but data on side effects were limited.In conclusion, (2R,6R)-HNK shows promise as a next-generation antidepressant. However, further research is needed to fully understand its long-term safety and mechanisms, and to determine its advantages over existing treatments like esketamine, particularly for TRD patients.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/NU21-04-00307" target="_blank" >NU21-04-00307: Psilocybin versus ketamin – strategie rychlé antidepresivní odpovědi u deprese rezistentní k léčbě</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmacology

ISSN

0014-2999

e-ISSN

1879-0712

Svazek periodika

999

Číslo periodika v rámci svazku

"Article Number 177604"

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

1-13

Kód UT WoS článku

001492009300001

EID výsledku v databázi Scopus

2-s2.0-105004941289