Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(1), P. 559 - 573

Published: May 7, 2021

The discovery of robust antidepressant actions exerted by the N-methyl-D-aspartate receptor (NMDAR) antagonist (R,S)-ketamine has been a crucial breakthrough in mood disorder research. is racemic mixture equal amounts (R)-ketamine (arketamine) and (S)-ketamine (esketamine). In 2019, an esketamine nasal spray from Johnson & was approved United States America Europe for treatment-resistant depression. However, increasing number preclinical studies show that arketamine greater potency longer-lasting antidepressant-like effects than rodents, despite lower binding affinity NMDAR. clinical trials, non-ketamine NMDAR-related compounds did not exhibit ketamine-like patients with depression, these showing rodents. Thus, rodent data do necessarily translate to humans due complexity human psychiatric disorders. Collectively, available indicate it unlikely NMDAR plays major role action its enantiomers, although precise molecular mechanisms underlying enantiomers remain unclear. this paper, we review recent findings on potent enantiomer arketamine. Furthermore, discuss possible brain-gut-microbiota axis brain-spleen stress-related disorders Finally, potential as treatment cognitive impairment disorders, Parkinson's disease, osteoporosis, inflammatory bowel diseases, stroke.

Language: Английский

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Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status

CNS Drugs, Journal Year: 2021, Volume and Issue: 35(5), P. 527 - 543

Published: April 26, 2021

Language: Английский

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Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review

Current Neuropharmacology, Journal Year: 2023, Volume and Issue: 22(4), P. 557 - 635

Published: May 3, 2023

Abstract: This narrative state-of-the-art review paper describes the progress in understanding and treatment of Posttraumatic Stress Disorder (PTSD). Over last four decades, scientific landscape has matured, with many interdisciplinary contributions to its diagnosis, etiology, epidemiology. Advances genetics, neurobiology, stress pathophysiology, brain imaging have made it apparent that chronic PTSD is a systemic disorder high allostatic load. The current state includes wide variety pharmacological psychotherapeutic approaches, which are evidence-based. However, myriad challenges inherent disorder, such as individual barriers good outcome, comorbidity, emotional dysregulation, suicidality, dissociation, substance use, trauma-related guilt shame, often render response suboptimal. These discussed drivers for emerging novel including early interventions Golden Hours, interventions, medication augmentation use psychedelics, well targeting nervous system. All this aims improve symptom relief clinical outcomes. Finally, phase orientation recognized tool strategize position step progression pathophysiology. Revisions guidelines systems care will be needed incorporate innovative treatments evidence emerges they become mainstream. generation well-positioned address devastating disabling impact traumatic events through holistic, cutting-edge efforts research.

Language: Английский

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Ketamine treatment for depression: a review

Discover Mental Health, Journal Year: 2022, Volume and Issue: 2(1)

Published: April 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.

Language: Английский

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Pharmacotherapy for post traumatic stress disorder (PTSD)

Cochrane library, Journal Year: 2022, Volume and Issue: 2022(3)

Published: March 2, 2022

Language: Английский

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The antidepressant actions of ketamine and its enantiomers

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 246, P. 108431 - 108431

Published: May 4, 2023

Language: Английский

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To Predict, Prevent, and Manage Post-Traumatic Stress Disorder (PTSD): A Review of Pathophysiology, Treatment, and Biomarkers

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5238 - 5238

Published: March 9, 2023

Post-traumatic stress disorder (PTSD) can become a chronic and severely disabling condition resulting in reduced quality of life increased economic burden. The is directly related to exposure traumatic event, e.g., real or threatened injury, death, sexual assault. Extensive research has been done on the neurobiological alterations underlying its phenotypes, revealing brain circuit disruption, neurotransmitter dysregulation, hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Psychotherapy remains first-line treatment option for PTSD given good efficacy, although pharmacotherapy also be used as stand-alone combination with psychotherapy. In order reduce prevalence burden disorder, multilevel models prevention have developed detect early possible morbidity those established diseases. Despite clinical grounds diagnosis, attention increasing discovery reliable biomarkers that predict susceptibility, aid monitor treatment. Several potential linked pathophysiological changes PTSD, encouraging further identify actionable targets. This review highlights current literature regarding pathophysiology, disease development models, modalities, preventive from public health perspective, discusses state biomarker research.

Language: Английский

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Ketamine in neuropsychiatric disorders: an update

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 49(1), P. 23 - 40

Published: June 20, 2023

Language: Английский

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Depression and Anxiety Disorders

Published: April 10, 2025

Abstract Depression (major depressive disorder) is widely recognised as a major public health problem around the world. The mainstay of treatment prescription antidepressants, although psychological treatments have place first‐line alternative to antidepressants in milder and moderate forms depression. This chapter concentrates on use offers advice drug choice, dosing, switching strategies sequencing treatments. near exclusion other non‐drug modalities does not imply any lack confidence their efficacy but simply reflects need (in prescribing guideline) concentrate medicines‐related subjects. Antidepressants are number anxiety spectrum disorders. Use selective serotonin reuptake inhibitors (SSRIs) preoperative period has been associated with 20% increase inpatient mortality, patient factors rather than could be excluded cause.

Language: Английский

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Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

Pharmacological Reports, Journal Year: 2021, Volume and Issue: 73(2), P. 323 - 345

Published: Feb. 20, 2021

Abstract Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, been studied used for several new indications, ranging from chronic pain to drug addiction post-traumatic stress disorder. The discovery of rapid-acting antidepressant effects resulted a surge interest towards understanding precise mechanisms driving effects. Indeed, may have had largest impact advancements research treatment psychiatric disorders few decades. While intense efforts aimed uncovering molecular targets underlying ketamine’s treating depression, neurobiological remain elusive. These are made more difficult by complex dose-dependent on mechanisms, multiple pharmacologically active metabolites, mechanism action associated facilitation synaptic plasticity. This review aims provide brief overview different uses ketamine, emphasis examining rapid spanning molecular, cellular, network levels. Another focus is offer perspective studies related doses research. Finally, discusses some latest hypotheses concerning action.

Language: Английский

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