Molecular Psychiatry
January 20, 2023
Jie Guo, Di Qiu, Han-Wen Gu et al.
46 citations
Perioperative intravenous ketamine reduces postoperative depression scores and pain scores on the first day after surgery but increases the risk of adverse effects including nausea, vomiting, headache, hallucination, and dizziness. The analysis of 15 randomized controlled trials with 1697 patients receiving ketamine and 1462 controls showed a reduction in depression scores on postoperative days 1, 3, and 7 and over the long term. Pain scores were lower only on the first postoperative day. The authors conclude that ketamine's benefits for postoperative depression and pain must be weighed against its increased adverse effects.
European journal of pharmacology
December 15, 2024
Ming-Ming Zhao, Ting-Ting Zhu, Dan Xu et al.
14 citations
Arketamine, the (R)-enantiomer of ketamine, reduces damage to the myelin sheath and promotes its repair in the brains of mice treated with cuprizone, a chemical that induces demyelination. The beneficial effects occur through a mechanism dependent on transforming growth factor β1 (TGF-β1). Blocking the TGF-β1 receptor with RepSox prevented arketamine's protective effects. Directly administering TGF-β1 intranasally also reduced demyelination and enhanced remyelination in the corpus callosum. These findings suggest that arketamine's effects on myelin repair rely on TGF-β1 signaling, pointing to potential therapeutic targets for demyelinating diseases like multiple sclerosis.
European archives of psychiatry and clinical neuroscience
April 25, 2024
Li-Yuan Zhao, Guang-Fen Zhang, Xue-Jie Lou et al.
11 citations
Over the past two decades, research on the antidepressant effects of ketamine and its enantiomers has grown substantially, culminating in the approval of esketamine nasal spray for treatment-resistant depression. A bibliometric analysis of 4,274 publications from 2000 to 2023, using visualization tools, reveals two main research foci: the efficacy and safety of these compounds in treating depression, and the mechanisms underlying their rapid antidepressant effects. The rapid onset of ketamine's effects has spurred further investigation into its mechanisms and the search for new antidepressants with fewer side effects.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Ting-Ting Zhu, Ming-Ming Zhao, Dan Xu et al.
5 citations
Postoperative cognitive dysfunction (POCD) involves declines in memory, attention, and executive abilities after surgery, with no effective drugs available. In a mouse model of POCD, a single injection of arketamine (10 mg/kg) improved cognitive function and reduced demyelination in the corpus callosum. Blocking TGF-β receptor 1 with RepSox (10 mg/kg) prevented these benefits, while intranasal TGF-β1 (3.0 μg/kg) alone alleviated cognitive impairments and demyelination. The findings indicate arketamine acts through a TGF-β1-dependent mechanism, suggesting it as a potential treatment for POCD.
Translational Psychiatry
May 20, 2026
Xin Ding, Rumi Murayama, Yi Cai et al.
1 citation
The drug combination KarXT (xanomeline plus trospium) reverses cognitive deficits caused by phencyclidine (PCP) in adult male mice, and this effect is linked to changes in gut and lung microbiota. PCP disrupted recognition memory and caused region-specific imbalances in microbes, especially in the small intestine and cecum. KarXT restored memory and normalized several bacterial species elevated by PCP, including Bacteroides fragilis and Veillonella ratti. Restoration of certain lung and gut microbes correlated with improved memory. The findings suggest that KarXT's cognitive benefits involve microbial modulation, which may guide efforts to reduce gastrointestinal side effects in muscarinic therapies for schizophrenia.
Translational psychiatry
November 24, 2025
Xin-Yu Li, Di Qiu, Ni Du et al.
1 citation
Patients with preexisting sleep disorders are at higher risk for postoperative sleep disturbance (PSD). In a randomized trial of 130 patients, intraoperative esketamine (0.3 mg/kg/h) reduced the incidence of PSD on postoperative day 1 (43.1% vs. 64.6%; odds ratio, 0.414) and lowered hydromorphone use. Preoperative oral microbiota profiles differed between patients who later developed PSD and those who did not, with specific bacterial taxa linked to sleep disturbance. The findings suggest esketamine may help prevent postoperative sleep disruption, possibly by modulating the oral microbiota.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Xin Ding, Kenji Hashimoto, Jian-Jun Yang
Xanomeline and ketamine, two mechanistically distinct antidepressants, partially converge on common molecular pathways despite acting through different upstream receptors. Network pharmacology and molecular docking identified 368 overlapping targets for xanomeline with major depressive disorder and 714 for ketamine. Three shared signaling pathways emerged: EGFR tyrosine kinase inhibitor resistance, Ras signaling, and Rap1 signaling. Three core proteins—EGFR, IGF1R, and SRC—were common to both drugs. Xanomeline associated more strongly with receptor tyrosine kinase and PI3K/AKT signaling, while ketamine linked more to synaptic transmission, NMDA receptors, and glutamatergic signaling. These hypothesis-generating findings suggest partial convergence on downstream plasticity-related signaling nodes.