Promising new pharmacological targets for depression: The search for efficacy

Tsugiyama, Lucila Emiko; Moraes, Ruan Carlos Macedo; Moraes, Yaslle Andrade Cavalcante; Francis-Oliveira, Jose

doi:10.1016/j.drudis.2023.103804

Cited by 6 publications

(3 citation statements)

References 291 publications

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“…Given that (R)-ketamine is currently under development as a rapid-acting antidepressant, this brief summary of the competitive landscape is meant to place (R)-ketamine in perspective as a developmental candidate for depression. A discussion of these data is available [2,9,24,25,30,51,52]. 5 AMPAR potentiator MDD and TRD Without dissociation or psychotomimetic effects 5-HT: 5-hydroxytryptamine or serotonin; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ASIB: acute suicidal ideation and behavior; GABA: gamma amino butyric acid; MDD: major depressive disorder; mGlu: metabotropic glutamate; NMDA: N-methyl-D-aspartate; PBA: pseudobulbar affect; PTSD: post-traumatic stress syndrome; TRD: treatment-resistant depression.…”

Section: Other Potential Rapid-acting Antidepressantsmentioning

confidence: 99%

Section: Other Potential Rapid-acting Antidepressantsmentioning

confidence: 99%

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(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

Shafique,

Demers,

Biesiada

et al. 2024

IJMS

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NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). (S)-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of (R)-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than (S)-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of (R)-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with (R)-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications.

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Section: Other Potential Rapid-acting Antidepressantsmentioning

confidence: 99%

Section: Other Potential Rapid-acting Antidepressantsmentioning

confidence: 99%

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

Shafique,

Demers,

Biesiada

et al. 2024

IJMS

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“…There are numerous risk factors associated with the onset of depression, including stress, pain, physical illnesses, and cognitive decline. Currently, scholars are primarily focusing on the pathophysiology of depression, particularly in relation to the monoaminergic system, the glutamatergic system, the hypothalamic-pituitary-adrenal axis, inflammation, gut microbiota, and neurogenesis ( Emiko Tsugiyama et al, 2023 ; Reyes-Lizaola et al, 2023 ). Since the 1950s, commonly used clinical antidepressant medications have primarily targeted the increase of serotonin or acted directly on serotonin receptors ( Murrough and Charney, 2012 ; Undurraga and Baldessarini, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients

Guo,

Long,

Yao

et al. 2024

Front. Pharmacol.

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Background: Depression is a severe mental disorder that poses a significant threat to both the physical and mental wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in both clinical and animal research.Objective: This review aims to provide a comprehensive synthesis of evidence related to CSS, considering both preclinical and clinical studies, to uncover its potential multi-level, multi-pathway, and multi-target mechanisms for treating depression and identify its active ingredients.Methods: A thorough search was conducted in electronic databases, including PubMed, MEDLINE, Web of Science, Google Scholar, CNKI, and Wanfang, using keywords such as “Chaihu Shugan” and “depression” to retrieve relevant literature on CSS and its active ingredients. The review process adhered to the PRISMA guidelines.Results: This review consolidates the mechanisms underlying antidepressant effects of CSS and its active ingredients. It emphasizes its involvement in the regulation of monoaminergic neurotransmitter systems, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis, among other aspects.Conclusion: CSS exerts a pivotal role in treating depression through various pathways, including the monoaminergic neurotransmitter system, the hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brain-derived neurotrophic factor levels, and the brain-gut axis. This review facilitates a comprehensive understanding of the current state of CSS research, fostering an in-depth exploration of the etiological mechanisms of depression and the potential discovery of novel antidepressant drugs.

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The emergence of antidepressant drugs targeting GABAA receptors: A concise review

Gonda,

Tarazi,

Dome

2024

Biochemical Pharmacology

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Promising new pharmacological targets for depression: The search for efficacy

Cited by 6 publications

References 291 publications

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients

The emergence of antidepressant drugs targeting GABAA receptors: A concise review

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