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Long-term effects of a single high-dose intraperitoneal injection of lipopolysaccharide on depression-like behavior in adolescent mice.
Neurosci Lett
November 2024
Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan.
The commonly used lipopolysaccharide (LPS)-induced depression models often evaluate depression-like behaviors in the acute phase after a single intraperitoneal injection of LPS, and are not suitable for examining long-term depression-like behaviors. To overcome this limitation, we developed a mice LPS model for elucidating the long-term pathophysiology of depression. Using the tail-suspension test, we show that a single intraperitoneal injection of a high dose (1.
View Article and Find Full Text PDFEvolving trends of pharmaceutical poisonings associated with QRS complex prolongation.
Clin Toxicol (Phila)
September 2024
American College of Medical Toxicology, Phoenix, AZ, USA.
Introduction: Tricyclic antidepressants often cause drug-induced QRS complex prolongation in overdose but are now less commonly prescribed. We sought to determine, among a contemporary cohort of patients, the pharmaceuticals independently associated with QRS complex prolongation in acute overdose.
Methods: We performed secondary analysis of data from the Toxicology Investigators Consortium (ToxIC) Core Registry.
3,3-Dibromoflavanone, a synthetic flavonoid derivative for pain management with antidepressant-like effects and fewer side effects than those of morphine in mice.
Chem Biol Interact
October 2024
Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Laboratorio de Neuro-Fito-Farmacología Medicinal, Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini, Facultad de Farmacia y Bioquímica, Junín 956 (C1113AAD), Buenos Aires, Argentina. Electronic address:
In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the μ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine.
View Article and Find Full Text PDFTricyclic and tetracyclic antidepressants upregulate VMAT2 activity and rescue disease-causing VMAT2 variants.
Neuropsychopharmacology
October 2024
Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Vesicular monoamine transporter 2 (VMAT2) is an essential transporter that regulates brain monoamine transmission and is important for mood, cognition, motor activity, and stress regulation. However, VMAT2 remains underexplored as a pharmacological target. In this study, we report that tricyclic and tetracyclic antidepressants acutely inhibit, but persistently upregulate VMAT2 activity by promoting VMAT2 protein maturation.
View Article and Find Full Text PDFGenetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.
IBRO Neurosci Rep
December 2024
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants.
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