2014
DOI: 10.1097/aln.0000000000000285
|View full text |Cite
|
Sign up to set email alerts
|

(R,S)-Ketamine Metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine Increase the Mammalian Target of Rapamycin Function

Abstract: Background Subanesthetic doses of (R,S)-ketamine are used in the treatment of neuropathic pain and depression. In the rat, the antidepressant effects of (R,S)-ketamine are associated with increased activity and function of mammalian target of rapamycin (mTOR); however, (R,S)-ketamine is extensively metabolized and the contribution of its metabolites to increased mTOR signaling is unknown. Methods Rats (n = 3/time point) were given (R,S)-ketamine, (R,S)-norketamine and (2S,6S)-hydroxynorketamine and their eff… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

4
130
0

Year Published

2014
2014
2024
2024

Publication Types

Select...
10

Relationship

1
9

Authors

Journals

citations
Cited by 104 publications
(134 citation statements)
references
References 24 publications
4
130
0
Order By: Relevance
“…Ketamine activates mammalian target of rapamycin (mTOR) signaling. [35][36][37][38] We therefore examined the possibility that inhibition of mTOR with rapamycin could prevent ketamineinduced impairment of LTP. We found that in the presence of rapamycin in the perfusion solution, LTP remained impaired in the NAc of ketamine-treated mice (10 mg kg − 1 1 day; without rapamycin: 109.9 ± 6.7; n = 15; with rapamycin: 200 nM: 109.5 ± 9.1; n = 9; with rapamycin: 1 μM: 95.1 ± 9.4; n = 5; P40.05, one-way analysis of variance, Dunnett's multiple comparison test; Figure 4a).…”
Section: 11mentioning
confidence: 99%
“…Ketamine activates mammalian target of rapamycin (mTOR) signaling. [35][36][37][38] We therefore examined the possibility that inhibition of mTOR with rapamycin could prevent ketamineinduced impairment of LTP. We found that in the presence of rapamycin in the perfusion solution, LTP remained impaired in the NAc of ketamine-treated mice (10 mg kg − 1 1 day; without rapamycin: 109.9 ± 6.7; n = 15; with rapamycin: 200 nM: 109.5 ± 9.1; n = 9; with rapamycin: 1 μM: 95.1 ± 9.4; n = 5; P40.05, one-way analysis of variance, Dunnett's multiple comparison test; Figure 4a).…”
Section: 11mentioning
confidence: 99%
“…The concentrations of ketamine and its metabolites in plasma and brain tissue were determined by achiral liquid chromatography-tandem mass spectrometry using a previously described protocol with slight modifications (Paul et al, 2014;Moaddel et al, 2015). For plasma samples, the calibration standards for (R,S)-ketamine, (R,S)-norketamine, (2R,6R; 2S,6S)-HNK, and (R,S)-DHNK ranged from 10,000 to 19.53 ng/ml.…”
Section: Tissue Distribution and Clearance Measurements Of Ketamine Amentioning
confidence: 99%
“…Stereomers (R,S) of ketamine and its metabolites norketamine and (2S,6S)-hydroxynorketamine increase phosphorylation of mTOR and its downstream targets Akt, ERK1/2, 70S6K, and 4E-BP1 in a cell culture model (Paul et al, 2014b). As mentioned earlier, the activation of mTOR pathways is crucial for synaptic plasticity.…”
Section: F N-methyl-d-aspartate Receptor Antagonistsmentioning
confidence: 94%