Biochemical Pharmacology, Год журнала: 2022, Номер 198, С. 114963 - 114963
Опубликована: Фев. 16, 2022
Язык: Английский
Journal of Neuroscience, Год журнала: 2023, Номер 43(6), С. 1038 - 1050
Опубликована: Янв. 3, 2023
Ketamine is a well-characterized NMDA receptor (NMDAR) antagonist, although the relevance of this pharmacology to its rapid (within hours administration) antidepressant actions, which depend on mechanisms convergent with strengthening excitatory synapses, unclear. Activation synaptic NMDARs necessary for induction canonical long-term potentiation (LTP) leading sustained expression increased strength. We tested hypothesis that effects requires NMDAR activation, by using behavioral pharmacology, western blot quantification hippocampal synaptoneurosomal protein levels, and
Язык: Английский
Процитировано
59
Neuropsychopharmacology, Год журнала: 2023, Номер 49(1), С. 51 - 66
Опубликована: Июнь 27, 2023
Abstract N-methyl-D-aspartate (NMDA) receptors mediate a slow component of excitatory synaptic transmission, are widely distributed throughout the central nervous system, and regulate plasticity. NMDA receptor modulators have long been considered as potential treatments for psychiatric disorders including depression schizophrenia, neurodevelopmental such Rett Syndrome, neurodegenerative conditions Alzheimer’s disease. New interest in therapeutic targets has spurred by findings that certain inhibitors produce surprisingly rapid robust antidepressant activity novel mechanism, induction changes brain well outlast presence drug body. These driving research into an entirely new paradigm using antagonists host related conditions. At same time positive allosteric being pursued enhancing function diseases feature hypofunction. While there is great promise, developing must also navigate significant risks posed use agents. We review here emerging pharmacology agents target different subtypes, offering avenues capturing targeting this important class.
Язык: Английский
Процитировано
56
Nature Mental Health, Год журнала: 2023, Номер 1(11), С. 876 - 886
Опубликована: Окт. 19, 2023
Язык: Английский
Процитировано
51
Molecular Psychiatry, Год журнала: 2024, Номер 29(4), С. 1114 - 1127
Опубликована: Янв. 4, 2024
Язык: Английский
Процитировано
16
Current Neuropharmacology, Год журнала: 2024, Номер 22(4), С. 636 - 735
Опубликована: Янв. 5, 2024
Post-traumatic stress disorder (PTSD) is a mental health condition that can occur following exposure to traumatic experience. An estimated 12 million U.S. adults are presently affected by this disorder. Current treatments include psychological therapies (e.g., exposure-based interventions) and pharmacological selective serotonin reuptake inhibitors (SSRIs)). However, significant proportion of patients receiving standard-of-care for PTSD remain symptomatic, new approaches other trauma-related conditions greatly needed. Psychedelic compounds alter cognition, perception, mood currently being examined their efficacy in treating despite current status as Drug Enforcement Administration (DEA)- scheduled substances. Initial clinical trials have demonstrated the potential value psychedelicassisted therapy treat psychiatric disorders. In comprehensive review, we summarize state science care, including shortcomings. We review studies psychedelic interventions PTSD, disorders, common comorbidities. The classic psychedelics psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT) DMT-containing ayahuasca, well entactogen 3,4-methylenedioxymethamphetamine (MDMA) dissociative anesthetic ketamine, reviewed. For each drug, present history use, somatic effects, pharmacology, safety profile. rationale proposed mechanisms use traumarelated disorders discussed. This concludes with an in-depth consideration future directions applications maximize therapeutic benefit minimize risk individuals communities impacted conditions.
Язык: Английский
Процитировано
16
American Journal of Psychiatry, Год журнала: 2025, Номер unknown
Опубликована: Янв. 15, 2025
Ketamine is a racemic compound and medication comprised of (S)-ketamine (R)-ketamine enantiomers its metabolites. It has been used for decades as dissociative anesthetic, analgesic, recreational drug. More recently, ketamine, enantiomers, metabolites have or are being investigated the treatment refractory depression, well comorbid disorders such anxiety, obsessive-compulsive, opioid use disorders. Despite complex pharmacology, ketamine referred to an N-methyl-d-aspartate (NMDA) receptor antagonist. In this review, authors argue that ketamine's pharmacology should be redefined include receptors endogenous system. They also highlight potential mechanism action depression attributed bifunctional, synergistic interactions involving NMDA receptors.
Язык: Английский
Процитировано
2
Neuropharmacology, Год журнала: 2022, Номер 218, С. 109219 - 109219
Опубликована: Авг. 14, 2022
The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)-ketamine causes rapid onset and sustained antidepressant actions in treatment-resistant patients with major depressive disorder (MDD) other psychiatric disorders, such as bipolar post-traumatic stress disorder. is a racemic mixture consisting of (R)-ketamine (or arketamine) (S)-ketamine esketamine), (S)-enantiomer having greater affinity for the NMDAR. In 2019, an esketamine nasal spray by Johnson & was approved USA Europe depression. contrast, increasing number preclinical studies show that arketamine has potency longer-lasting antidepressant-like effects than rodents, despite lower binding Importantly, side effects, i.e., psychotomimetic dissociative abuse liability, are less those animals humans. An open-label study demonstrated MDD. A phase 2 clinical trial MDD underway. This designed to review brief history novel arketamine, molecular mechanisms underlying its actions, future directions. article part Special Issue on 'Ketamine Metabolites'.
Язык: Английский
Процитировано
69
MedComm, Год журнала: 2022, Номер 3(3)
Опубликована: Июль 21, 2022
Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand molecular pathophysiology of depression, it still unclear. Current treatments for depression are inadequate individuals, because limited effectiveness, delayed efficacy (usually two weeks), side effects. Consequently, novel drugs with increased speed action effectiveness required. Ketamine has shown have rapid, reliable, long-lasting antidepressant effects in treatment-resistant MDD patients represent breakthrough therapy MDD; however, concerns regarding its efficacy, potential misuse, remain. In this review, we aimed summarize mechanisms pharmacological depression. We focused on fast treatment clarified safety, tolerability, ketamine metabolites treatment, along review mechanisms, research challenges, future clinical prospects.
Язык: Английский
Процитировано
66
Neuropharmacology, Год журнала: 2023, Номер 226, С. 109418 - 109418
Опубликована: Янв. 6, 2023
Psychiatric disorders associated with psychological trauma, stress and anxiety are a highly prevalent increasing cause of morbidity worldwide. Current therapeutic approaches, including medication, effective in alleviating symptoms posttraumatic disorder (PTSD), at least some individuals, but have unwanted side-effects do not resolve underlying pathophysiology. After period stagnation, there is renewed enthusiasm from public, academic commercial parties designing developing drug treatments for these disorders. Here, we aim to provide snapshot the current state this field that written neuropharmacologists, also practicing clinicians interested lay-reader. introducing currently available treatments, summarize recent/ongoing clinical assessment novel medicines PTSD, grouped according primary neurochemical targets their potential produce acute and/or enduring effects. The evaluation putative targeting monoamine (including psychedelics), GABA, glutamate, cannabinoid, cholinergic neuropeptide systems, amongst others, discussed. We emphasize importance clinically assessing new medications based on firm understanding neurobiology stemming rapid advances being made neuroscience. This includes harnessing neuroplasticity bring about lasting beneficial changes brain rather than – as many transient attenuation symptoms, exemplified by combining psychotropic/cognitive enhancing drugs psychotherapeutic approaches. conclude noting other emerging trends promising phase development.
Язык: Английский
Процитировано
37
Therapeutic Advances in Psychopharmacology, Год журнала: 2023, Номер 13
Опубликована: Янв. 1, 2023
Background: More than 2% of the general population experience suicidal ideas each year and a large number them will attempt suicide. Evidence-based therapeutic options to manage crisis are currently limited. Objectives: The aim this study was overview findings on use ketamine esketamine for treatment acts. Design: Systematic review. Data Sources methods: PubMed, article references, Clinicaltrials.gov up June 30, 2022. Meta-analyses published within last 2 years were also reviewed. Results: We identified 12 randomized controlled trials with reduction ideation as primary objective 14 secondary objectives. Intravenous racemic superior control drugs (placebo or midazolam) first 72 h, in spite placebo effects. Adverse events minor transient. In contrast, intranasal did not differ from large-scale studies. Limitations, clinical considerations, opportunities future research include following points: effects when studying reduction; small concerns about blinding quality due dissociative effects; no studies risk/prevention acts mortality; lack beyond affective disorders; adolescents older people; knowledge long-term side effects, notably liability abuse; robust predictive markers; limited understanding mechanisms ideas; need improved assessment trials; outpatient settings, emergency room, liaison consultation; administration; positive negative concomitant treatments. Conclusion: Overall, there is compelling evidence favorable short-term benefit-risk balance intravenous but esketamine. place have be defined multimodal care strategy patients. Caution remains necessary use, pharmacovigilance essential.
Язык: Английский
Процитировано
33