Pharmacology Corner

Lorman, William J.

doi:10.1097/jan.0000000000000315

Cited by 7 publications

(3 citation statements)

References 2 publications

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“…Ketamine can cause hallucinations, hepatotoxicity, neurotoxicity, addiction, and other side effects, significantly limiting its clinical application. Agomepratine has no significant improvement in the treatment of depression in over one-third of patients (Perrine et al, 2014;Lorman, 2019). At the same time, although chemicals regulating endocrine metabololism such as metformin have been proven to have an antidepressant effect in preclinical and clinical studies.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Antidepressant pharmacological mechanisms: focusing on the regulation of autophagy

Lv,

Zhang,

Huang

et al. 2023

Front. Pharmacol.

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The core symptoms of depression are anhedonia and persistent hopelessness. Selective serotonin reuptake inhibitors (SSRIs) and their related medications are commonly used for clinical treatment, despite their significant adverse effects. Traditional Chinese medicine with its multiple targets, channels, and compounds, exhibit immense potential in treating depression. Autophagy, a vital process in depression pathology, has emerged as a promising target for intervention. This review summarized the pharmacological mechanisms of antidepressants by regulating autophagy. We presented insights from recent studies, discussed current research limitations, and proposed new strategies for basic research and their clinical application in depression.

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Section: Strengths and Limitationsmentioning

confidence: 99%

Antidepressant pharmacological mechanisms: focusing on the regulation of autophagy

Lv,

Zhang,

Huang

et al. 2023

Front. Pharmacol.

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“…In addition, ( rac )-ketamine has poor oral bioavailability that necessitates parenteral dosing. Spravato ® (esketamine), an intranasal formulation of the more potent S -enantiomer of ketamine, has been approved for patients with treatment-resistant depression, but still requires supervised administration under a restrictive Risk Evaluation and Mitigation Strategy (REMS) program due to sedative and dissociative effects [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents

Klein,

Austin,

Cunningham

et al. 2024

Neuropsychopharmacol.

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The NMDA receptor (NMDAR) antagonist ketamine has shown great potential as a rapid-acting antidepressant; however, its use is limited by poor oral bioavailability and a side effect profile that necessitates in-clinic dosing. GM-1020 is a novel NMDAR antagonist that was developed to address these limitations of ketamine as a treatment for depression. Here, we present the preclinical characterization of GM-1020 alongside ketamine, for comparison. In vitro, we profiled GM-1020 for binding to NMDAR and functional inhibition using patch-clamp electrophysiology. In vivo, GM-1020 was assessed for antidepressant-like efficacy using the Forced Swim Test (FST) and Chronic Mild Stress (CMS), while motor side effects were assessed in spontaneous locomotor activity and on the rotarod. The pharmacokinetic properties of GM-1020 were profiled across multiple preclinical species. Electroencephalography (EEG) was performed to determine indirect target engagement and provide a potentially translational biomarker. These results demonstrate that GM-1020 is an orally bioavailable NMDAR antagonist with antidepressant-like efficacy at exposures that do not produce unwanted motor effects.

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“…[7][8][9][10] Since the application of molecular biology in medicine, nonmonoamine drugs, such as ketamine and angomelatine, have become one of the most popular drugs, which are effective in relieving symptoms and improving prognosis of patients with depression. 11,12 Despite this, the therapeutic effect of existing mainstream antidepressants still has considerable limitations, such as SSRIs taking several weeks to take effect, the drug cycle is long, and it is easy to relapse, and some patients do not respond to various drugs. Therefore, it is particularly important to find new treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Targeting Mitochondrial Homeostasis: The Role of Acupuncture in Depression Treatment

Chen¹,

Wu²,

Lv³

et al. 2023

NDT

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Background: Depression is a common mental health disorder characterized by persistent feelings of sadness, loss of interest or pleasure, and a range of physical and cognitive symptoms. It affects people of all ages and can significantly impact their daily functioning and quality of life. Mitochondrial homeostasis plays an important role in the pathogenesis of depression. Mitochondrial homeostasis includes mitophagy, mitochondrial oxidative stress, mitoptosis, mitochondrial biogenesis, and mitochondrial dynamics. The regulation of mitochondrial homeostasis is the key link in the prevention and treatment of depression. Methods: In this article, we focus on the core link of depression-mitochondrial homeostasis and summarize the research progress of acupuncture targeting mitochondrial homeostasis in the treatment of depression in recent years, so as to provide ideas and experimental basis for the research and formulation of more appropriate depression treatment strategies. Results: Acupuncture has been found to regulate mitochondrial homeostasis (by modulating mitochondrial autophagy, reducing mitochondrial oxidative stress, inhibiting mitochondrial fission, inducing mitochondrial biogenesis, and maintaining mitochondrial dynamics), alleviate depression-like behavior, and regulate signal pathways and key proteins. Conclusion: Here, we highlight the role of acupuncture in the treatment of depression. A comprehensive exploration of the impact of acupuncture on mitochondrial homeostasis could potentially present a novel mechanism for treating depression and offer fresh perspectives for the treatment of patients with clinical depression.

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Pharmacology Corner

Cited by 7 publications

References 2 publications

Antidepressant pharmacological mechanisms: focusing on the regulation of autophagy

Antidepressant pharmacological mechanisms: focusing on the regulation of autophagy

GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents

Targeting Mitochondrial Homeostasis: The Role of Acupuncture in Depression Treatment

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