Ketamine - precursor of a new generation antidepressant drugs DOI Creative Commons
Jolanta B. Zawilska, Ewa Zwierzyńska

Farmacja Polska, Journal Year: 2024, Volume and Issue: 80(1), P. 51 - 62

Published: April 17, 2024

Zaburzenia depresyjne są jednymi z najczęściej występujących chorób psychicznych na świecie. Leczenie depresji stanowi ważny problem medyczny, a strategie farmakologiczne oparte wyrównywaniu zaburzeń transmisji monoaminergicznych w mózgu wiążą się opóźnionym czasie efektem przeciwdepresyjnym. Ponadto, coraz większy odsetek pacjentów cierpi depresję lekooporną, gdzie pomimo wdrożenia leczenia przeciwdepresyjnego nie dochodzi do remisji choroby. Wyniki badań ostatnich lat wskazują, że za rozwój mogą odpowiadać zaburzenia plastyczności neuronalnej, przywrócenie prawidłowej neuroplastyczności może skutkować szybkim działaniem Ketamina jest pierwszym lekiem, który charakteryzuje takim działaniem. Ten dożylny lek znieczulenia ogólnego niekompetycyjnym antagonistą receptorów glutaminianergicznych typu NMDA. Zablokowanie NMDA zlokalizowanych hamujących interneuronach GABA-ergicznych prowadzi uwalniania glutaminianu. W wyniku pobudzenia postsynaptycznych AMPA aktywacji syntezy czynnika wzrostu pochodzenia mózgowego (BDNF). BDNF pobudzając receptory TrkB uruchamia kaskadę wewnątrzkomórkowych procesów biochemicznych, których odbudowy synaps, także zwiększenia liczby i poprawienia funkcjonowania połączeń synaptycznych. Niektóre badania ketamina przywracać prawidłową plastyczność neuronalną również poprawy równowagi pomiędzy wzbudzeniem hamowaniem mikroobwodach neuronalnych mózgu. blokując postsynaptyczne hipokampie hamuje aktywność nadmiernie pobudzonej kinazy eEF2K, odblokowuje syntezę białek synaptycznych przywraca neuronalną. Szerokie zastosowanie ketaminy jako leku oraz zmniejszającego myśli zachowania samobójcze ograniczone ze względu jej działania niepożądane, przede wszystkim psychozomimetyczne. Z tego prowadzono nad wykorzystaniem leczeniu enancjomerów ketaminy: (S+)-ketaminy (esketaminy) (R-)-ketaminy (arketaminy), które potencjalnie miałyby korzystniejsze profile bezpieczeństwa. Obecnie esketamina (spray nosa) zarejestrowana u dorosłych lekoopornej endogennej lub myślami zachowaniami samobójczymi. terapii esketaminę stosuje łącznie doustnym lekiem przeciwdepresyjnym (SSRI SNRI). Odkrycie skuteczności przeciwdepresyjnej zmieniło podejście neurobiologicznych podstaw depresyjnych zapoczątkowało nowy kierunek depresją. Należy jednakże pamiętać o tym, dużych dawkach wywiera poważne toksyczne, stosowana związek halucynogenny.

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, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 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

Language: Английский

Citations

29

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders DOI Open Access
Noemi Nicosia, M. Giovenzana, Paulina Misztak

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6521 - 6521

Published: June 13, 2024

Glutamate is the main excitatory neurotransmitter in brain wherein it controls cognitive functional domains and mood. Indeed, areas involved memory formation consolidation as well fear emotional processing, such hippocampus, prefrontal cortex, amygdala, are predominantly glutamatergic. To ensure physiological activity of brain, glutamatergic transmission finely tuned at synaptic sites. Disruption mechanisms responsible for glutamate homeostasis may result accumulation excessive levels, which turn leads to increased calcium mitochondrial abnormalities, oxidative stress, eventually cell atrophy death. This condition known glutamate-induced excitotoxicity considered a pathogenic mechanism several diseases central nervous system, including neurodevelopmental, substance abuse, psychiatric disorders. On other hand, these disorders share neuroplasticity impairments areas, accompanied by structural remodeling neurons. In current narrative review, we will summarize role both pathophysiology therapeutic interventions neurodevelopmental adult mental with focus on autism spectrum disorders, drugs under preclinical clinical development treatment different that dysfunctions. Although evidence still limited more studies required, regulation attracting attention potential crucial target control diseases.

Language: Английский

Citations

22

The neurobiology of stress: Vulnerability, resilience, and major depression DOI Creative Commons
Huda Akil, Eric J. Nestler

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(49)

Published: Nov. 27, 2023

The global agri-food system is simultaneously a major contributor to, and severely affected by, climate change. Agroecological farming systems can contribute to creating resilient systems. Based on multiyear qualitative case study, ...Supporting transitions sustainable, important ensure stable food supply in the face of growing extremes. Agroecology, or diversified based ecological principles, such ...

Language: Английский

Citations

35

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction DOI Creative Commons
Yousef Tizabi, Bruk Getachew, Sheketha R. Hauser

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 558 - 558

Published: May 30, 2024

Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.

Language: Английский

Citations

13

Decoding Neural Circuit Dysregulation in Bipolar Disorder: Toward an Advanced Paradigm for Multidimensional Cognitive, Emotional, and Psychomotor Treatment DOI Creative Commons

Luca Steardo,

Martina D’Angelo, Francesco Monaco

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: 169, P. 106030 - 106030

Published: Feb. 1, 2025

Bipolar disorder (BD) is characterized by a complex constellation of emotional, cognitive, and psychomotor disturbances, each deeply intertwined with underlying dysfunctions in large-scale brain networks neurotransmitter systems. This manuscript integrates recent advances neuroimaging, neuromodulation, pharmacological research to provide comprehensive view BD's pathophysiology, emphasizing the role network-specific their clinical manifestations. We explore how dysregulation within fronto-limbic network, particularly involving prefrontal cortex (PFC) amygdala, underpins emotional instability that defines both manic depressive episodes. Additionally, impairments central executive network (CEN) default mode (DMN) are linked cognitive deficits, hyperactivity DMN driving rumination inflexibility, while CEN underactivity contributes attentional lapses impaired function. Psychomotor symptoms, which oscillate between mania retardation depression, closely associated imbalances systems, dopamine serotonin, basal ganglia-thalamo-cortical motor pathway. Recent studies indicate these disturbances further exacerbated disruptions connectivity, leading control regulation. Emerging therapeutic strategies discussed, focus on neuromodulation techniques such as transcranial magnetic stimulation (TMS) deep (DBS), show promise restoring balance critical networks. Furthermore, interventions modulate synaptic functioning neuronal plasticity offer potential for addressing symptoms BD. underscores need an integrative treatment approach simultaneously targets neural circuits systems address full spectrum Drawing advancements neurobiological models frameworks, this proposal outlines pathway development precision-tailored interventions. These approaches designed optimize outcomes, ultimately striving elevate quality life individuals living bipolar (BD), remaining firmly grounded latest empirical evidence theoretical insights.

Language: Английский

Citations

2

Gamma oscillations and excitation/inhibition imbalance: parallel effects of N-methyl D-aspartate receptor antagonism and psychosis DOI Creative Commons
Brian J. Roach,

Judith M. Ford,

Spero Nicholas

et al.

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed schizophrenia and rodent studies of N-methyl D-aspartate glutamate receptor (NMDAR) hypofunction. However, extent to which ASSR resemble deficits induced by acute administration ketamine, an NMDAR antagonist, is not yet known. To address this knowledge gap, we conducted parallel EEG studies: a crossover, placebo-controlled ketamine drug challenge study healthy subjects (Study 1) comparison patients with controls 2). Time-frequency analysis was used calculate baseline, broadband gamma power, evoked total phase-locking factor, angle. Relative controls, exhibited increases pre-stimulus power reductions replicating prior studies. failed replicate previous findings phase delay schizophrenia. placebo, ketamine: increased reduced advanced ASSR. Normalized their respective control groups/conditions, direct these measures between data only revealed significant differences phase, supporting role hypofunction mediating oscillation

Language: Английский

Citations

1

Esketamine at a Clinical Dose Attenuates Cerebral Ischemia/Reperfusion Injury by Inhibiting AKT Signaling Pathway to Facilitate Microglia M2 Polarization and Autophagy DOI Creative Commons
Ying Gao, Lu Li,

Fang Zhao

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 369 - 387

Published: Jan. 1, 2025

This study aimed to assess the protective effect of a clinical dose esketamine on cerebral ischemia/reperfusion (I/R) injury and reveal potential mechanisms associated with microglial polarization autophagy. Experimental ischemia was induced by middle artery occlusion (MCAO) in adult rats simulated oxygen-glucose deprivation (OGD) BV-2 cells. Neurological sensorimotor function, infarct volume, histopathological changes, mitochondrial morphological apoptosis ischemic brain tissues were assessed presence or absence autophagy inducer rapamycin. The expression biomarkers related M1 M2 phenotypes determined immunofluorescence staining RT-qPCR, proteins AKT signaling pathway assayed Western blotting. Esketamine alone combined rapamycin alleviated neurological impairment, improved decreased mitigated tissue MCAO rats. Importantly, promoted phenotypic transition from both OGD-treated microglia, autophagy, inactivated signaling. Furthermore, effects enhanced addition at attenuates I/R inhibiting facilitate can provide an protection against injury. Thus, this provides new insights into neuroprotective therapeutic strategies

Language: Английский

Citations

1

Rapid hippocampal synaptic potentiation induced by ketamine metabolite (2R,6R)-hydroxynorketamine persistently primes synaptic plasticity DOI
Kyle A. Brown, Musa Iyiola Ajibola, Todd D. Gould

et al.

Neuropsychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

1

A Real-World Study on the Use, Effectiveness, and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression: INTEGRATE Study DOI
Patricio Molero, Ángela Ibáñez, Javier de Diego-Adeliño

et al.

Advances in Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

Citations

1

Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care DOI Creative Commons
Connor T. A. Brenna, Benjamin I. Goldstein, Carlos A. Zarate

et al.

Anesthesiology, Journal Year: 2024, Volume and Issue: 141(2), P. 222 - 237

Published: June 10, 2024

During the last 100 years, role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium other perioperative neurocognitive disorders. The discovery rapid sustained antidepressant properties ketamine, early results suggesting that general anesthetic drugs (including nitrous oxide, propofol, isoflurane) have properties, positioned at a new frontier treatment neuropsychiatric Moreover, shared interest understanding biologic underpinnings as psychotropic agents is eroding traditional academic boundaries between anesthesiology psychiatry. This article presents brief overview novel antidepressants identifies promising future candidates for depression. authors issue call to action outline strategies foster collaborations psychiatrists they work toward common goals repurposing addressing mood disorders surgical patients.

Language: Английский

Citations

8