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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GABAA receptors as targets for treating affective and cognitive symptoms of depression

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(9), P. 586 - 600

Published: Aug. 3, 2023

Language: Английский

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Targeting metaplasticity mechanisms to promote sustained antidepressant actions

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(4), P. 1114 - 1127

Published: Jan. 4, 2024

Language: Английский

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Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments

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

Published: Nov. 27, 2023

Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy treatment-resistant symptoms, protection against relapse distinguish it from prior antidepressants. discovery reconceptualization the neurobiology depression and, in turn, insights elaboration its mechanisms action inform studies pathophysiology related disorders. It been 25 y since we first presented our ketamine findings Thus, is timely this review to consider what have learned suggest future directions optimization rapid-acting antidepressant treatment.

Language: Английский

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GluN2A mediates ketamine-induced rapid antidepressant-like responses

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(10), P. 1751 - 1761

Published: Sept. 14, 2023

Language: Английский

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Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice

Science Signaling, Journal Year: 2024, Volume and Issue: 17(834)

Published: April 30, 2024

Signaling mediated by brain-derived neurotrophic factor (BDNF), which is supported the postsynaptic scaffolding protein PSD-95, has antidepressant effects. Conversely, clinical depression associated with reduced BDNF signaling. We found that peptidomimetic compounds bind to PSD-95 promoted signaling receptor TrkB in hippocampus and depression-like behaviors mice. The CN2097 Syn3 both PDZ3 domain of also binds an α-helical region protein. two mouse models stress-induced depression; had similar but less potent In hippocampal neurons, application enhanced formation TrkB-Gαi1/3-PSD-95 complexes potentiated downstream PI3K-Akt-mTOR mice subjected chronic mild stress (CMS), systemic administration reversed CMS-induced, depression-associated changes signaling, dendrite complexity, spine density, autophagy behaviors. Knocking out Gαi1/3 neurons prevented therapeutic effects Syn3, indicating dependence these on pathway. findings suggest induce PSD-95-TrkB have potential alleviate depression.

Language: Английский

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Targeting N-Methyl-d-Aspartate Receptors in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3733 - 3733

Published: March 27, 2024

-methyl-d-aspartate receptors (NMDARs) are the main class of ionotropic for excitatory neurotransmitter glutamate. They play a crucial role in permeability Ca

Language: Английский

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Demystifying the Antidepressant Mechanism of Action of Stinels, a Novel Class of Neuroplastogens: Positive Allosteric Modulators of the NMDA Receptor

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 157 - 157

Published: Jan. 24, 2025

Plastogens are a class of therapeutics that function by rapidly promoting changes in neuroplasticity. A notable example, ketamine, is receiving great attention due to its combined rapid and long-term antidepressant effects. Ketamine an N-methyl-D-aspartate receptor (NMDAR) antagonist, and, addition therapeutic activity, it associated with psychotomimetic dissociative side Stinels—rapastinel, apimostinel, zelquistinel—are also plastogens not only effects but improved safety tolerability profiles compared ketamine. Previous descriptions the mechanism which stinels modulate NMDAR activity have been inconsistent at times, contradictory. The purpose this review clarify action contextualize within broader NMDAR-targeting therapeutics. In review, we present rationale behind targeting NMDARs for treatment-resistant depression other psychiatric conditions, describe various mechanisms regulated different classes therapeutics, evidence stinel mechanism. contrast previous glycine-like partial agonists, define as positive allosteric modulators novel regulatory binding site.

Language: Английский

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Rapid hippocampal synaptic potentiation induced by ketamine metabolite (2R,6R)-hydroxynorketamine persistently primes synaptic plasticity

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

Published: March 17, 2025

Language: Английский

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