Uncovering the Underlying Mechanisms of Ketamine as a Novel Antidepressant DOI Creative Commons
Songbai Xu, Xiaoxiao Yao, Bingjin Li

и другие.

Frontiers in Pharmacology, Год журнала: 2022, Номер 12

Опубликована: Июль 7, 2022

Major depressive disorder (MDD) is a devastating psychiatric which exacts enormous personal and social-economic burdens. Ketamine, an N -methyl-D-aspartate receptor (NMDAR) antagonist, has been discovered to exert rapid sustained antidepressant-like actions on MDD patients animal models. However, the dissociation psychotomimetic propensities of ketamine have limited its use for indications. Here, we review recently proposed mechanistic hypotheses regarding how exerts actions. Ketamine may potentiate α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPAR)-mediated transmission in pyramidal neurons by disinhibition and/or blockade spontaneous NMDAR-mediated neurotransmission. also activate neuroplasticity- synaptogenesis-relevant signaling pathways, converge key components like brain-derived neurotrophic factor (BDNF)/tropomyosin kinase B (TrkB) target rapamycin (mTOR). These processes subsequently rebalance excitatory/inhibitory restore neural network integrity that compromised depression. Understanding mechanisms underpinning ketamine’s at cellular circuit level will drive development safe effective pharmacological interventions treatment MDD.

Язык: Английский

Brain–gut–microbiota axis in depression: A historical overview and future directions DOI Creative Commons
Lijia Chang, Wei Yan, Kenji Hashimoto

и другие.

Brain Research Bulletin, Год журнала: 2022, Номер 182, С. 44 - 56

Опубликована: Фев. 11, 2022

Depression is the most common mental disorder and a leading cause of disability worldwide. Despite abundant research, precise mechanisms underlying pathophysiology depression remain elusive. Accumulating evidence from preclinical clinical studies suggests that alterations in gut microbiota, microbe-derived short-chain fatty acids, D-amino acids metabolites play key role via brain–gut–microbiota axis, including neural immune systems. Notably, axis might crucial susceptibility versus resilience rodents exposed to stress. Vagotomy reported block depression-like phenotypes after fecal microbiota transplantation "depression-related" microbiome, suggesting vagus nerve influences through axis. In this article, we review recent findings regarding discuss its potential as therapeutic target for depression.

Язык: Английский

Процитировано

244
Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine DOI Creative Commons
Wei Yao, Qianqian Cao, Shilin Luo

и другие.

Molecular Psychiatry, Год журнала: 2021, Номер 27(3), С. 1618 - 1629

Опубликована: Ноя. 24, 2021

Abstract ( R,S )-ketamine elicits rapid-acting and sustained antidepressant actions in treatment-resistant patients with depression. R produces longer-lasting effects than S rodents; however, the precise molecular mechanisms underlying of remain unknown. Using isobaric Tag for Relative Absolute Quantification, we identified nuclear receptor-binding protein 1 (NRBP1) that could contribute to different antidepressant-like two enantiomers chronic social defeat stress (CSDS) model. NRBP1 was localized microglia neuron, not astrocyte, mouse medial prefrontal cortex (mPFC). increased expression NRBP1, brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding (p-CREB)/CREB ratio primary cultures thorough extracellular signal-regulated kinase (ERK) activation. Furthermore, activate BDNF transcription through activation CREB as well MeCP2 (methyl-CpG 2) suppression microglia. Single intracerebroventricular (i.c.v.) injection CREB-DNA/RNA heteroduplex oligonucleotides (CREB-HDO) or exon IV-HDO blocked CSDS susceptible mice. Moreover, microglial depletion by colony-stimulating receptor (CSF1R) inhibitor PLX3397 In addition, inhibition single i.c.v. mannosylated clodronate liposomes (MCLs) significantly Finally, CREB-HDO, MCLs beneficial on reduced dendritic spine density mPFC These data suggest a novel ERK-NRBP1-CREB-BDNF pathways )-ketamine.

Язык: Английский

Процитировано

158
Mechanisms of ketamine and its metabolites as antidepressants DOI
Evan Hess, Lace M. Riggs, Michael Michaelides

и другие.

Biochemical Pharmacology, Год журнала: 2021, Номер 197, С. 114892 - 114892

Опубликована: Дек. 27, 2021

Язык: Английский

Процитировано

116
Ketamine treatment for depression: a review DOI Creative Commons
Mani Yavi, Holim Lee, Ioline D. Henter

и другие.

Discover Mental Health, Год журнала: 2022, Номер 2(1)

Опубликована: Апрель 15, 2022

Abstract This manuscript reviews the clinical evidence regarding single-dose intravenous (IV) administration of novel glutamatergic modulator racemic ( R,S )-ketamine (hereafter referred to as ketamine) well its S -enantiomer, intranasal esketamine, for treatment major depressive disorder (MDD). Initial studies found that a single subanesthetic-dose IV ketamine infusion rapidly (within one day) improved symptoms in individuals with MDD and bipolar depression, antidepressant effects lasting three seven days. In 2019, esketamine received FDA approval an adjunctive treatment-resistant depression (TRD) adults. Esketamine was approved under risk evaluation mitigation strategy (REMS) requires medical supervision. Both are currently viable options TRD offer possibility rapid symptom improvement. The also ketamine’s use other psychiatric diagnoses—including suicidality, obsessive–compulsive disorder, post-traumatic stress substance abuse, social anxiety disorder—and potential adverse effects. Despite limited data, side antidepressant-dose ketamine—including dissociative symptoms, hypertension, confusion/agitation—appear be tolerable around time treatment. Relatively little is known about longer-term effects, including increased risks abuse and/or dependence. Attempts prolong combined therapy or repeat-dose reviewed, current guidelines use. addition presenting valuable option, studying has transform our understanding mechanisms underlying mood disorders development therapeutics.

Язык: Английский

Процитировано

85
Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy DOI Creative Commons

Di Qiu,

Xingming Wang,

Jin-Jin Yang

и другие.

JAMA Network Open, Год журнала: 2022, Номер 5(12), С. e2244514 - e2244514

Опубликована: Дек. 1, 2022

Importance Postoperative sleep disturbance (PSD) is common in patients after surgery. Objective To examine the effect of intraoperative esketamine infusion on incidence PSD who underwent gynecological laparoscopic Design, Setting, and Participants This single-center, double-blind, placebo-controlled randomized clinical trial was conducted from August 2021 to April 2022 First Affiliated Hospital Zhengzhou University China. included aged 18 65 years with an American Society Anesthesiologist Physical Status classification I III (with indicating a healthy patient, II patient mild systemic disease, severe disease) Patients were randomly assigned either group or control group. Data analyzed using per protocol principle. Interventions received continuous esketamine, 0.3 mg/kg/h, intraoperatively. equivalent volume saline. Main Outcomes Measures The primary outcome postoperative days (PODs) 1 3. defined as numeric rating scale score 6 higher Athens Insomnia Scale points higher. secondary outcomes anxiety depression scores Anxiety Depression Scale, pain visual analog scale, hydromorphone consumption, risk factors associated PSD. Results A total 183 female (n = 91; median [IQR] age, 45 [35-49] years) 92; 43 [32-49] years). significantly lower than POD (22.8% vs 44.0%; odds ratio [OR], 0.38 [95% CI, 0.20-0.72]; P .002) 3 (7.6% 19.8%; OR, 0.33 0.13-0.84]; .02). There no differences between 2 groups. consumption first 24 hours (3.0 [range, 2.8-3.3] mg 3.2 2.9-3.4] mg; .04) movement (3 [3-4] 4 [3-5] points; < .001) On multivariable logistic regression, preoperative (OR, 1.31; 95% 1.01-1.70) 1.67; 1.04-1.80) scores, duration anesthesia 1.04; 1.00-1.08), 1.92; 1.24-2.96) identified Conclusions Relevance this showed prophylactic Further studies are needed confirm these results. Trial Registration Chinese Clinical Registry Identifier: ChiCTR2100048587

Язык: Английский

Процитировано

72
The antidepressant actions of ketamine and its enantiomers DOI
Jenessa N. Johnston, Ioline D. Henter, Carlos A. Zarate

и другие.

Pharmacology & Therapeutics, Год журнала: 2023, Номер 246, С. 108431 - 108431

Опубликована: Май 4, 2023

Язык: Английский

Процитировано

72
A Look at the Importance of Chirality in Drug Activity: Some Significative Examples DOI Creative Commons
Jessica Ceramella, Domenico Iacopetta,

Angelica Franchini

и другие.

Applied Sciences, Год журнала: 2022, Номер 12(21), С. 10909 - 10909

Опубликована: Окт. 27, 2022

Chirality plays an important role in the development of many pharmaceuticals, being a general property ‘handedness’; nevertheless, large number pharmaceuticals are still marketed and administered as racemates. is all around even within us; indeed, receptors enzymes chiral entities interact specific manner with drugs. Consequently, controlling enantiomeric purity isolating enantiomers from drugs remains crucial subject for analytical, clinical, regulatory purposes, thus, improving drug safety profile. The classical examples spontaneous enantiomerization severe toxicity related to chirality represented by ibuprofen thalidomide, respectively, but numerous other cases have been reported literature. This review intends offer brief overview on most common used therapy treatment various diseases.

Язык: Английский

Процитировано

71
Randomized trial of ketamine masked by surgical anesthesia in patients with depression DOI Open Access
Theresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr

и другие.

Nature Mental Health, Год журнала: 2023, Номер 1(11), С. 876 - 886

Опубликована: Окт. 19, 2023

Язык: Английский

Процитировано

51
Ketamine in neuropsychiatric disorders: an update DOI
Jenessa N. Johnston, Bashkim Kadriu, Christoph Kraus

и другие.

Neuropsychopharmacology, Год журнала: 2023, Номер 49(1), С. 23 - 40

Опубликована: Июнь 20, 2023

Язык: Английский

Процитировано

48
Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? DOI Creative Commons
Kenji Hashimoto

European Archives of Psychiatry and Clinical Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Фев. 27, 2024

The growing interest in the rapid and sustained antidepressant effects of dissociative anesthetic ketamine classic psychedelics, such as psilocybin, is remarkable. However, both psychedelics are known to induce acute mystical experiences; can cause symptoms out-of-body experience, while typically bring about hallucinogenic experiences, like a profound sense unity with universe or nature. role these experiences enhancing outcomes for patients depression currently an area ongoing investigation debate. Clinical studies have shown that following administration (S)-ketamine (esketamine) not directly linked their properties. In contrast, potential (R)-ketamine (arketamine), thought lack side effects, has yet be conclusively proven large-scale clinical trials. Moreover, although activation serotonin 5-HT

Язык: Английский

Процитировано

28