(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders DOI Open Access
Hana Shafique,

Julie Demers,

Julia Biesiada

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6804 - 6804

Published: June 20, 2024

NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative epilepsy, traumatic brain injury, substance abuse disorder (SUD), major depressive (MDD). (S)-ketamine was the first of a novel class antidepressants, rapid-acting to be approved medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development treatment-resistant depression (TRD). compound has demonstrated efficacy multiple animal models. Two clinical studies disclosed TRD bipolar depression. A study by drug sponsor recently failed reach priori endpoints but post hoc analysis revealed efficacy. value supported experimental data humans rodents, showing that it less sedating, does not produce marked psychotomimetic or dissociative effects, than (S)-ketamine, produces models range disorders. mechanisms action antidepressant effects are hypothesized due antagonism and/or non-NMDA mechanisms. We suggest further experimentation with will create improved medicines some disorders underserved current medications.

Language: Английский

Saffron essential oil ameliorates CUMS-induced depression-like behavior in mice via the MAPK-CREB1-BDNF signaling pathway DOI
Ziwei Chen, Jinping Gu,

Susu Lin

et al.

Journal of Ethnopharmacology, Journal Year: 2022, Volume and Issue: 300, P. 115719 - 115719

Published: Sept. 17, 2022

Language: Английский

Citations

46
(R)-ketamine as prophylactic and therapeutic drug for neurological disorders: Beyond depression DOI Creative Commons

Xingming Wang,

Jianjun Yang, Kenji Hashimoto

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 139, P. 104762 - 104762

Published: June 30, 2022

Neurological disorders are the leading cause of disability and second death worldwide. The increasing social economic burdens neurological driven by global population growth aging. Depression is a common psychiatric symptom in numerous disorders. It also risk factor for Alzheimer's disease (AD) other dementias, Parkinson's (PD), stroke. rapid-acting sustained antidepressant actions (R,S)-ketamine severe depression was accidentally discovered. Interestingly, (R)-ketamine has greater potency longer-lasting antidepressant-like effects than (S)-ketamine rodents. Importantly, its side rodents humans lower those (S)-ketamine. Furthermore, could elicit beneficial various rodent models disorders, including PD, multiple sclerosis (MS), In this article, we review potential as prophylactic or therapeutic drug AD MS,

Language: Английский

Citations

41
Inflammation, stress and depression: An exploration of ketamine’s therapeutic profile DOI Creative Commons
Jenessa N. Johnston, Maximillian Greenwald, Ioline D. Henter

et al.

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(4), P. 103518 - 103518

Published: Feb. 8, 2023

Language: Английский

Citations

37
Noteworthy perspectives on microglia in neuropsychiatric disorders DOI Creative Commons
Hongrui Zhu,

Ao Guan,

Jiayuan Liu

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Oct. 4, 2023

Abstract Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions behaviors. have a profound impact on neuronal survival, wiring synaptic plasticity. As professional phagocytic cells brain, remove dead cell debris neurotoxic agents via an elaborate mechanism. The functional profile microglia varies considerately depending age, gender, disease context other internal or external environmental factors. Numerous studies demonstrated pivotal involvement neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain symptoms associated with major depression disorder, anxiety autism spectrum disorder schizophrenia. In this review, we summarized latest discoveries regarding microglial ontogeny, subtypes state spectrum, biological functions mechanistic underpinnings emotional behavioral disorders. Furthermore, highlight potential microglia-targeted therapies propose outstanding questions to be addressed future research human microglia.

Language: Английский

Citations

37
Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment DOI Creative Commons
Jenessa N. Johnston, Bashkim Kadriu, Josh Allen

et al.

Neuropharmacology, Journal Year: 2023, Volume and Issue: 226, P. 109422 - 109422

Published: Jan. 13, 2023

Language: Английский

Citations

33
Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics DOI Creative Commons
Shaoyi Fang,

Zhibin Wu,

Yali Guo

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 10, 2023

Adult hippocampal neurogenesis generates functional neurons from neural progenitor cells in the dentate gyrus (DG) to complement and repair circuits, thus benefiting treatment of depression. Increasing evidence has shown that aberrant microglial activity can disrupt appropriate formation development properties neurogenesis, which will play a crucial role occurrence However, mechanisms crosstalk between microglia adult depression are not yet fully understood. Therefore, this review, we first introduce recent discoveries regarding roles etiology Then, systematically discuss possible how regulate according studies, involve toll-like receptors, polarization, fractalkine-C-X3-C motif chemokine receptor 1, hypothalamic-pituitary-adrenal axis, cytokines, brain-derived neurotrophic factor, microbiota-gut-brain etc. In addition, summarize promising drugs could improve by regulating microglia. These findings help us understand complicated pathological shed light on new strategies for disease.

Language: Английский

Citations

33
Arketamine for cognitive impairment in psychiatric disorders DOI Creative Commons
Kenji Hashimoto

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2023, Volume and Issue: 273(7), P. 1513 - 1525

Published: Feb. 14, 2023

Cognitive impairment has been observed in patients with various psychiatric disorders, including schizophrenia, major depressive disorder (MDD), and bipolar (BD). Although modern therapeutic drugs can improve certain symptoms (i.e., psychosis, depression) these patients, have not found to cognitive impairment. The N-methyl-D-aspartate receptor antagonist (R,S)-ketamine attracted attention as a rapidly acting antidepressant. In addition its robust antidepressant effects, suggested MDD BD, despite causing healthy control subjects. is racemic mixture of equal amounts (R)-ketamine (or arketamine) (S)-ketamine esketamine). Arketamine more potent antidepressant-like actions than esketamine rodents. Interestingly, arketamine, but esketamine, phencyclidine-induced deficits mice. Furthermore, arketamine ameliorate rodent offspring after maternal immune activation. the current article, it proposed that potential for treating disorders. Additionally, role gut-microbiome-brain axis disorders discussed.

Language: Английский

Citations

32
Neuroinflammation through the vagus nerve-dependent gut–microbiota–brain axis in treatment-resistant depression DOI
Kenji Hashimoto

Progress in brain research, Journal Year: 2023, Volume and Issue: unknown, P. 61 - 77

Published: Jan. 1, 2023

Language: Английский

Citations

31
Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies DOI Creative Commons
Jie Guo,

Di Qiu,

Hanwen Gu

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 20, 2023

Abstract Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy safety of perioperative application ketamine on postoperative depression remains uncertain. We performed meta-analysis to determine effect intravenous administration depression. Randomized controlled trials comparing with placebo in patients were included. Primary outcome was scores. Secondary outcomes included visual analog scale (VAS) scores for pain adverse effects associated ketamine. Fifteen studies 1697 receiving 1462 controls enrolled. Compared controls, group showed reduction scores, by standardized mean difference (SMD) −0.97, 95% confidence interval [CI, −1.27, −0.66], P < 0.001, I 2 = 72% day (POD) 1; SMD−0.65, CI [−1.12, −0.17], 94% POD 3; SMD−0.30, [−0.45, −0.14], 0% OD 7; SMD−0.25, [−0.38, −0.11], 59% over long term. Ketamine reduced VAS 1 (SMD−0.93, [−1.58, −0.29], 0.005, 97%), but no significant found between two groups PODs 3 7 or distinctly increased risk effects, including nausea vomiting (risk ratio [RR] 1.40, [1.12, 1.75], 0.003, 30%), headache (RR 2.47, [1.41, 4.32], 0.002, 19%), hallucination 15.35, [6. 4, 37.34], 89%), dizziness 3.48, [2.68, 4.50], 89%) compared controls. In conclusion, reduces effects.

Language: Английский

Citations

27
Molecular mechanisms of rapid-acting antidepressants: New perspectives for developing antidepressants DOI Creative Commons
Tao Chen,

Ling Cheng,

Jingwen Ma

et al.

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106837 - 106837

Published: June 26, 2023

Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds the patients are prone relapse symptoms or completely ineffective in antidepressant treatment. The recent success N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as rapid-acting has propelled extensive research on action mechanism antidepressants, especially relation its role synaptic targets. Studies have revealed that not limited antagonism postsynaptic NMDA receptors GABA interneurons. Ketamine produces powerful and rapid effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic receptors, adenosine A1 L-type calcium channels, among others synapse. More interestingly, 5-HT2A agonist psilocybin demonstrated potential for depressed mouse models clinical studies. This article focuses review new pharmacological target studies emerging drugs such hallucinogens (e.g., psilocybin) briefly discusses possible strategies targets with view shed light direction future research.

Language: Английский

Citations

26