The interaction of gallamine with muscarinic receptors from different tissues has been investigated. Gallamine binds to a site distinct from the conventional muscarinic ligand binding site and modulates the binding of agonists and antagonists to the conventional binding site. In agreement with reported pharmacological studies, the effects of gallamine on the binding of muscarinic ligands are much greater in heart than in other tissues. These findings suggest the possibility of developing novel and selective muscarinic drugs.
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Curr Alzheimer Res
January 2025
Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Fujian, 361000, China.
Introduction: Muscarinic 1 acetylcholine receptor (M1AChR) is a member of the Gprotein- coupled receptor superfamily, with the dysfunction being linked to the onset of Alzheimer's Disease (AD).
Aims: Retromer complex with Vacuolar Protein Sorting-35 (VPS35) as the core plays an important role in the transport of biological proteins and has been confirmed to be closely related to the pathogenesis of AD. This study was designed to determine whether VPS35 could affect the trafficking mechanism of M1AChRs.
Acta Naturae
January 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997 Russian Federation.
The secreted human protein SLURP-2 is a regulator of epithelial homeostasis, which enhances the viability and migration of keratinocytes. The targets of SLURP-2 in keratinocytes are nicotinic and muscarinic acetylcholine receptors. This work is devoted to the search for the SLURP-2 functional regions responsible for enhancing keratinocyte viability and migration.
View Article and Find Full Text PDFRespir Med
January 2025
Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
The increasing global elderly population, projected to reach 20% of individuals aged 65 and over by 2030, faces significant pulmonary challenges, including chronic obstructive pulmonary disease (COPD). Aging is associated with a natural decline in lung function and structural changes that exacerbate respiratory issues. COPD, characterized by chronic respiratory symptoms and airflow obstruction, presents a unique challenge in older patients due to the accelerated decline in lung function.
View Article and Find Full Text PDFGeorgian Med News
November 2024
Lab. Neurobiology of Sleep-Wakefulness Cycle, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia.
Aim: The present investigation aimed to explore in rats the early postnatal dysfunction of the brain muscarinic cholinergic system (EPDMChS) during the most vulnerable period of postnatal development, as the possible main factor for changes in adult hippocampal neurogenesis and disorders in hippocampus-dependent spatial learning and memory.
Methods: White inbred rats (n=15 in each group) were used. EPDMCHS was produced by a new method, which includes early postnatal blocking of M1-M5 muscarinic acetylcholine receptors in the rat pups, using subcutaneous injection of Scopolamine during postnatal days 7-28.
F1000Res
January 2025
German Center for Mental Health (DZPG), partner site München/Augsburg, Munich, Germany.
Background: Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.
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