Pharmacology, Biochemistry and Behavior
June 1, 2019
Lijia Chang, Kai Zhang, Yaoyu Pu et al.
174 citations
In a mouse model of chronic social defeat stress, a single intranasal dose of (R)-ketamine produced stronger antidepressant effects than (R,S)-ketamine or (S)-ketamine. Conversely, (S)-ketamine caused the greatest increase in locomotor activity and deficits in prepulse inhibition, followed by (R,S)-ketamine, while (R)-ketamine showed the least. In conditioned place preference tests, repeated intranasal (S)-ketamine and (R,S)-ketamine increased preference scores dose-dependently, indicating abuse liability, whereas (R)-ketamine did not. These findings suggest intranasal (R)-ketamine may be a safer antidepressant option.
Translational Psychiatry
January 27, 2020
Kai Zhang, Chun Yang, Lijia Chang et al.
120 citations
In mice with depression-like symptoms from chronic social defeat stress, (R)-ketamine produced more potent and longer-lasting antidepressant effects than (S)-ketamine. RNA sequencing of the prefrontal cortex showed that transforming growth factor (TGF)-β signaling may explain these differences. (R)-ketamine, but not (S)-ketamine, reversed reduced expression of Tgfb1 and its receptors in the prefrontal cortex and hippocampus. Blocking TGF-β1 with inhibitors or a neutralizing antibody prevented (R)-ketamine's antidepressant effects. Depleting microglia also blocked these effects. Recombinant TGF-β1 itself produced rapid and lasting antidepressant effects in mice, suggesting a microglial TGF-β1-dependent mechanism and potential for new human antidepressants.
Neuropharmacology
October 1, 2022
Kai Zhang, Yitan Yao, K. Hashimoto
68 citations
Ketamine can rapidly relieve depressive symptoms within hours of a single dose, even in patients who do not respond to traditional antidepressants, which often take weeks to work. However, the specific mechanisms behind this rapid effect are not fully understood, and ketamine is associated with serious side effects like dissociative symptoms, cognitive impairment, and abuse potential. This review examines ketamine's pharmacological properties and proposed mechanisms of action, including the disinhibition hypothesis, synaptogenesis, and downstream pathways such as enhanced brain-derived neurotrophic factor signaling and activation of mechanistic target of rapamycin complex 1. (R)-ketamine may offer a safer alternative with fewer adverse effects, and understanding these mechanisms could help develop new rapid antidepressants that maximize benefits while minimizing risks.
Drug design, development and therapy
January 1, 2024
Mengcao Weng, Dongdong Wang, Jia Zhong et al.
17 citations
For hysteroscopy, the 95% effective dose (ED95) of esketamine combined with propofol was 0.254 mg/kg, while alfentanil's ED95 was 9.121 μg/kg. In a randomized trial, the anesthesia success rate with these ED95 doses was 93.0% for esketamine and 95.2% for alfentanil, with no significant difference. Induction time was shorter with esketamine (60 seconds) than alfentanil (67 seconds). Esketamine caused significantly lower rates of respiratory depression, hypoxia, and hypotension, and had less effect on breathing and blood pressure. Postoperative pain did not differ between groups. Esketamine is an effective and safer alternative to alfentanil for hysteroscopic anesthesia.
European archives of psychiatry and clinical neuroscience
September 28, 2024
Yue Wang, Qiongyao Yang, Chuanchuan Chen et al.
10 citations
After six low-dose esketamine infusions, patients with treatment-resistant depression showed improvement in anhedonia and depressive symptoms. Plasma levels of cortisol, interleukin-6, and tumor necrosis factor-alpha decreased, while the anti-inflammatory cytokine interleukin-4 increased. Baseline cortisol levels correlated with anhedonia, but inflammatory factors showed no significant correlation. Elevated plasma cortisol may serve as a potential biomarker for anhedonia in treatment-resistant depression.
BMC psychiatry
May 12, 2025
Zouqing Lin, Xiaoyan Xu, Kai Zhang et al.
3 citations
Patients with first-episode or recurrent major depressive disorder (MDD) had higher levels of plasma MICB and larger splenic volume compared to healthy controls matched for age and gender. A positive correlation existed between MICB and splenic volume in the patient group. After treatment with (S)-ketamine, both elevated splenic volume and MICB levels decreased, suggesting that abnormal MICB expression and splenic morphology may be involved in MDD pathogenesis and that (S)-ketamine may reduce inflammation and improve splenic function.
Journal of affective disorders
January 15, 2025
Qiongyao Yang, Yitan Yao, Xiaoping Yuan et al.
3 citations
In patients with depression, six intravenous infusions of esketamine (0.4 mg/kg) over 11 days significantly reduced depressive symptoms, with mean Montgomery-Asberg Depression Rating Scale scores dropping from 32.11 to 15.10. Memory function—including immediate memory, language, attention, and delayed memory—improved, and plasma nerve growth factor (NGF) levels rose from 226.13 to 384.37 pg/mL. A positive correlation existed between baseline memory function and NGF levels, while higher baseline memory was linked to smaller NGF increases. These findings suggest NGF may contribute to esketamine's memory-enhancing effects, though the open-label design limits certainty.