المؤلفون: Zhengxing Zhi, Gang Xing, Maosheng Cheng, Bin Lin, Ce Yi, Peiyuan Dou

المصدر: Expert Opinion on Therapeutic Patents. 31:239-246

مصطلحات موضوعية: Muscarinic Antagonists, 01 natural sciences, β2 adrenergic receptor, Patents as Topic, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Drug Development, Smooth muscle, Drug Discovery, Animals, Humans, Medicine, Receptor, Adrenergic beta-2 Receptor Agonists, G protein-coupled receptor, Pharmacology, business.industry, food and beverages, General Medicine, Asthma, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, 030220 oncology & carcinogenesis, business, Neuroscience

الوصف: The β2 adrenergic receptor (β2AR) is a member of G protein-coupled receptors (GPCRs) that mediate the majority of cellular responses to external stimuli. The agonists can cause smooth muscle relaxa...

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::adf55e3dd52661976ac0d600d56029e8Test
https://doi.org/10.1080/13543776.2021.1865312Test

المؤلفون: Masato Mashimo, Yoshika Fukuda, Marina Fujii, Natsumi Sakagawa, Rika Imanaka, Takeshi Fujii

المصدر: Biologicalpharmaceutical bulletin. 43(12)

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_treatment, Pharmaceutical Science, Immunoglobulins, Muscarinic Antagonists, Immunoglobulin G, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Muscarinic acetylcholine receptor, medicine, Humans, Receptor, B cell, Acetylcholine receptor, Pharmacology, B-Lymphocytes, biology, Chemistry, Interleukin-6, Interleukin, General Medicine, Molecular biology, Receptors, Muscarinic, 030104 developmental biology, medicine.anatomical_structure, Cytokine, Immunoglobulin class switching, 030220 oncology & carcinogenesis, biology.protein

الوصف: B cells express muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs, respectively). Following immunization with ovalbumin, serum immunoglobulin G (IgG) and interleukin (IL)-6 levels were lower in M1 and M5 mAChR double-deficient mice and higher in α7 nAChR-deficient mice than in wild-type mice. This suggests mAChRs participate in the cytokine production involved in B cell differentiation into plasma cells, which induces immunoglobulin class switching from IgM to IgG. However, because these results were obtained with conventional knockout mice, in which all cells in the body were affected, the specific roles of these receptors expressed in B cells remains unclear. In the present study, Daudi B lymphoblast cells were used to investigate the specific roles of mAChRs and nAChR in B cells. Stimulating Daudi cells using Pansorbin cells (heat-killed, formalin-fixed Staphylococcus aureus coated with protein A) upregulated expression of M1-M4 mAChRs and the α4 nAChR subunit. Under these conditions, mAChRs, but not nAChRs, mediated immunoglobulin class switching to IgG. This effect was blocked by scopolamine, a non-selective mAChR antagonist, and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a Gq/11-coupled M1, M3, M5 antagonist. In addition, IL-6 secretion was further enhanced following mAChR activation. Thus, Gq/11-coupled mAChRs expressed in B cells thus appear to contribute to IL-6 production and B cell maturation into IgG-producing plasma cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc4fd26e85e853bdf3f3c2738f0e8771Test
https://pubmed.ncbi.nlm.nih.gov/33268714Test

المؤلفون: Monika Kustermann, Svenja Laue, Yinghong Cui, Douglas G. Tilley, Laurel A. Grisanti, Melanie Rothe, Michael Kauk, Carsten Hoffmann, Melanie Philipp, WH Zimmermann, Teresa Casar Tena, Allessandra Moretti, Farah Raad, Michael Kühl, Martina S. Burczyk, Sabrina Matysik, Martin D. Burkhalter, Cornelia Donow, Jürgen Wess

المصدر: JCI Insight

مصطلحات موضوعية: 0301 basic medicine, Embryo, Nonmammalian, Tolterodine Tartrate, Organogenesis, Muscarinic Antagonists, Mice, Xenopus laevis, 03 medical and health sciences, 0302 clinical medicine, Heart Conduction System, Muscarinic acetylcholine receptor, Heart rate, medicine, Animals, Humans, Myocytes, Cardiac, Receptor, Zebrafish, Mice, Knockout, Receptor, Muscarinic M3, Sinoatrial node, business.industry, fungi, Muscarinic acetylcholine receptor M3, Arrhythmias, Cardiac, General Medicine, Embryo, Mammalian, medicine.disease, 3. Good health, Disease Models, Animal, HEK293 Cells, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Heart failure, Atrioventricular canal, Electrical conduction system of the heart, business, Neuroscience, Research Article

الوصف: Deterioration or inborn malformations of the cardiac conduction system (CCS) interfere with proper impulse propagation in the heart and may lead to sudden cardiac death or heart failure. Patients afflicted with arrhythmia depend on antiarrhythmic medication or invasive therapy, such as pacemaker implantation. An ideal way to treat these patients would be CCS tissue restoration. This, however, requires precise knowledge regarding the molecular mechanisms underlying CCS development. Here, we aimed to identify regulators of CCS development. We performed a compound screen in zebrafish embryos and identified tolterodine, a muscarinic receptor antagonist, as a modifier of CCS development. Tolterodine provoked a lower heart rate, pericardiac edema, and arrhythmia. Blockade of muscarinic M3, but not M2, receptors induced transcriptional changes leading to amplification of sinoatrial cells and loss of atrioventricular identity. Transcriptome data from an engineered human heart muscle model provided additional evidence for the contribution of muscarinic M3 receptors during cardiac progenitor specification and differentiation. Taken together, we found that muscarinic M3 receptors control the CCS already before the heart becomes innervated. Our data indicate that muscarinic receptors maintain a delicate balance between the developing sinoatrial node and the atrioventricular canal, which is probably required to prevent the development of arrhythmia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d95a3d11c2efe67a92a1fc8c1ec423aTest
https://doi.org/10.1172/jci.insight.121971Test

المؤلفون: Michael Decker, Ulrike Holzgrabe

المصدر: Expert Opinion on Therapeutic Patents. 27:121-125

مصطلحات موضوعية: 0301 basic medicine, Stereochemistry, Allosteric regulation, Muscarinic Antagonists, Muscarinic Agonists, Ligands, Patents as Topic, 03 medical and health sciences, chemistry.chemical_compound, Drug Discovery, Muscarinic acetylcholine receptor, medicine, Functional selectivity, Humans, Receptor, Benzoic acid, Pharmacology, Chemistry, General Medicine, Neuromuscular Blocking Agents, Receptors, Muscarinic, 030104 developmental biology, Drug Design, Selectivity, Allosteric Site, Acetylcholine, medicine.drug

الوصف: Bitopic M ligands, that is, ligands that interact both with the ortho- and allosteric binding sites of the M receptor subtypes, hold great potential as novel selective for muscarinic acetylcholine (M) ligands for several therapeutic applications. Areas covered: The patent application describes a set of compounds based on the neurotransmitter acetylcholine applying the Schulman-model for M ligands comprising heterocyclic (often quaternary) amines and a benzene ring (often as benzoic acid esters) to act as bitopic ligands. The compounds claimed hold functional selectivity and are supposed to be therapeutically applied as neuromuscular blocking agents, in asthma as well as CNS diseases. In vitro evaluations of selected compounds supported bitopic binding and some degree of functional selectivity was observed - albeit no selectivity was observed in binding studies. Expert opinion: The quaternary amine structure of the compounds claimed will prohibit penetration into the CNS and their ester structure will lead to significant metabolic instability which will hamper therapeutic applications for many indications. Furthermore, high affinity and subtype selectivity with regard to binding affinity which is observed for bitopic and allosteric ligands in the current literature is not observed for the compounds described in the patent.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc3d3f30b52505cc487ddb5ce3d946a4Test
https://doi.org/10.1080/13543776.2017.1272577Test

المؤلفون: Mithat Gonen, Young Rock Chung, Omar Abdel-Wahab, Lillian Bitner, Gaurang Trivedi, Justin Taylor, Jürgen Wess, Daichi Inoue, Lingbo Zhang, Cynthia Chen

المصدر: Sci Transl Med

مصطلحات موضوعية: Erythrocytes, Muscarinic Antagonists, Biology, CREB, Article, Mice, Erythroid Cells, hemic and lymphatic diseases, Muscarinic acetylcholine receptor, Animals, Humans, Erythropoiesis, Progenitor cell, Cell Self Renewal, Receptor, Transcription factor, Erythroid Precursor Cells, Acetylcholine receptor, Stem Cells, Anemia, General Medicine, Receptors, Muscarinic, Cell biology, Mice, Inbred C57BL, Haematopoiesis, Gene Expression Regulation, biology.protein

الوصف: Adult stem and progenitor cells are uniquely capable of self-renewal, and targeting this process represents a potential therapeutic opportunity. The early erythroid progenitor, burst-forming unit erythroid (BFU-E), has substantial self-renewal potential and serves as a key cell type for the treatment of anemias. However, our understanding of mechanisms underlying BFU-E self-renewal is extremely limited. Here, we found that the muscarinic acetylcholine receptor, cholinergic receptor, muscarinic 4 (CHRM4), pathway regulates BFU-E self-renewal and that pharmacological inhibition of CHRM4 corrects anemias of myelodysplastic syndrome (MDS), aging, and hemolysis. Genetic down-regulation of CHRM4 or pharmacologic inhibition of CHRM4 using the selective antagonist PD102807 promoted BFU-E self-renewal, whereas deletion of Chrm4 increased erythroid cell production under stress conditions in vivo. Moreover, muscarinic acetylcholine receptor antagonists corrected anemias in mouse models of MDS, aging, and hemolysis in vivo, extending the survival of mice with MDS relative to that of controls. The effects of muscarinic receptor antagonism on promoting expansion of BFU-Es were mediated by cyclic AMP induction of the transcription factor CREB, whose targets up-regulated key regulators of BFU-E self-renewal. On the basis of these data, we propose a model of hematopoietic progenitor self-renewal through a cholinergic-mediated "hematopoietic reflex" and identify muscarinic acetylcholine receptor antagonists as potential therapies for anemias associated with MDS, aging, and hemolysis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24f59361c573e1cabd6a557f2e13f30dTest
https://pubmed.ncbi.nlm.nih.gov/31554738Test

المؤلفون: Naoto Hoshi, Anastasia Kosenko, Seungwoo Kang, Derek L. Greene, Hee Yeon Kay

المصدر: The Journal of clinical investigation, vol 125, iss 10

مصطلحات موضوعية: Male, medicine.medical_treatment, A Kinase Anchor Proteins, Action Potentials, Neurodegenerative, Phenylenediamines, Pharmacology, Inbred C57BL, Medical and Health Sciences, Hippocampus, Mice, chemistry.chemical_compound, Epilepsy, Muscarinic acetylcholine receptor, M current, Drug Interactions, Phosphorylation, Cells, Cultured, Anthracenes, Neurons, Valproic Acid, Cultured, Kainic Acid, Retigabine, General Medicine, 5.1 Pharmaceuticals, Neurological, Anticonvulsants, Female, lipids (amino acids, peptides, and proteins), Development of treatments and therapeutic interventions, medicine.symptom, Receptor, Research Article, Signal Transduction, medicine.drug, Kainic acid, Cells, Lipoylation, Recombinant Fusion Proteins, Immunology, Muscarinic Antagonists, Superior Cervical Ganglion, Muscarinic Agonists, Seizures, Potassium Channel Blockers, medicine, Animals, Humans, KCNQ2 Potassium Channel, Protein Processing, Receptor, Muscarinic M1, Post-Translational, Neurosciences, medicine.disease, Brain Disorders, Rats, Mice, Inbred C57BL, Anticonvulsant, Mechanism of action, chemistry, Muscarinic M1, Carbamates, Protein Processing, Post-Translational

الوصف: Valproic acid (VPA) has been widely used for decades to treat epilepsy; however, its mechanism of action remains poorly understood. Here, we report that the anticonvulsant effects of nonacute VPA treatment involve preservation of the M-current, a low-threshold noninactivating potassium current, during seizures. In a wide variety of neurons, activation of Gq-coupled receptors, such as the m1 muscarinic acetylcholine receptor, suppresses the M-current and induces hyperexcitability. We demonstrated that VPA treatment disrupts muscarinic suppression of the M-current and prevents resultant agonist-induced neuronal hyperexcitability. We also determined that VPA treatment interferes with M-channel signaling by inhibiting palmitoylation of a signaling scaffold protein, AKAP79/150, in cultured neurons. In a kainate-induced murine seizure model, administration of a dose of an M-channel inhibitor that did not affect kainate-induced seizure transiently eliminated the anticonvulsant effects of VPA. Retigabine, an M-channel opener that does not open receptor-suppressed M-channels, provided anticonvulsant effects only when administered prior to seizure induction in control animals. In contrast, treatment of VPA-treated mice with retigabine induced anticonvulsant effects even when administered after seizure induction. Together, these results suggest that receptor-induced M-current suppression plays a role in the pathophysiology of seizures and that preservation of the M-current during seizures has potential as an effective therapeutic strategy.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52e342ece078cc114a100a3f031b5abfTest
https://doi.org/10.1172/jci79727Test

المؤلفون: Osamu Nishiyama, Hiroaki Kume, Takaaki Isoya, Yukihiro Noda, Yuji Tohda, Yuji Higashimoto

المصدر: International Journal of Molecular Sciences
Volume 19
Issue 7
International Journal of Molecular Sciences, Vol 19, Iss 7, p 1999 (2018)

مصطلحات موضوعية: 0301 basic medicine, Male, Intrinsic activity, β2-adrenoceptor agonists, Pharmacology, lcsh:Chemistry, Potassium Channels, Calcium-Activated, large-conductance Ca2+-activated K+ channels, Muscarinic acetylcholine receptor, Receptor, lcsh:QH301-705.5, Spectroscopy, Chemistry, Muscarinic acetylcholine receptor M2, General Medicine, Computer Science Applications, Trachea, Atropine, synergistic effects, L-type voltage-dependent Ca2+ channels, medicine.drug, G protein, Procaterol, Allosteric regulation, Guinea Pigs, Muscarinic Antagonists, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Allosteric Regulation, medicine, COPD, Animals, Physical and Theoretical Chemistry, Molecular Biology, muscarinic receptor antagonists, Adrenergic beta-2 Receptor Agonists, Receptor, Muscarinic M2, Organic Chemistry, Muscle, Smooth, asthma, respiratory tract diseases, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Receptors, Adrenergic, beta-2

الوصف: To advance the development of bronchodilators for asthma and chronic obstructive pulmonary disease (COPD), this study was designed to investigate the mechanism of functional antagonism between &beta
2-adrenergic and muscarinic M2 receptors, focusing on allosteric effects and G proteins/ion channels coupling. Muscarinic receptor antagonists (tiotropium, glycopyrronium, atropine) synergistically enhanced the relaxant effects of &beta
2-adrenergic receptor agonists (procaterol, salbutamol, formoterol) in guinea pig trachealis. This crosstalk was inhibited by iberitoxin, a large-conductance Ca2+-activated K+ (KCa) channel inhibitor, whereas it was increased by verapamil, a L-type voltage-dependent Ca2+ (VDC) channel inhibitor
additionally, it was enhanced after tissues were incubated with pertussis or cholera toxin. This synergism converges in the G proteins (Gi, Gs)/KCa channel/VDC channel linkages. Muscarinic receptor antagonists competitively suppressed, whereas, &beta
2-adrenergic receptor agonists noncompetitively suppressed muscarinic contraction. In concentration-inhibition curves for &beta
2-adrenergic receptor agonists with muscarinic receptor antagonists, EC50 was markedly decreased, and maximal inhibition was markedly increased. Hence, muscarinic receptor antagonists do not bind to allosteric sites on muscarinic receptors. &beta
2-Adrenergic receptor agonists bind to allosteric sites on these receptors
their intrinsic efficacy is attenuated by allosteric modulation (partial agonism). Muscarinic receptor antagonists enhance affinity and efficacy of &beta
2-adrenergic action via allosteric sites in &beta
2-adrenergic receptors (synergism). In conclusion, KCa channels and allosterism may be novel targets of bronchodilator therapy for diseases such as asthma and COPD.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26d31c33c2a52479bb7a0b24088ba389Test
http://europepmc.org/articles/PMC6073859Test

المؤلفون: Mahmoud Saifeddine, Morley D. Hollenberg, Koichiro Mihara, William K. Stell, Brittany J. Carr, Rithwik Ramachandran, Neil M. Nathanson

المصدر: Physiology and Pharmacology Publications

مصطلحات موضوعية: Off-target, 0301 basic medicine, Atropine, Muscarinic antagonist, Muscarinic Antagonists, Pharmacology, Cholinergic Agonists, Ligands, Transfection, Dicyclomine, Clonidine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Receptors, Adrenergic, alpha-2, CRISPR-Associated Protein 9, Muscarinic acetylcholine receptor, medicine, Adrenergic alpha-2 Receptor Agonists, Myopia, Animals, Humans, Receptor, Receptor, Muscarinic M3, Receptor, Muscarinic M4, Nonspecific binding, Antagonist, General Medicine, Pirenzepine, Receptors, Muscarinic, Form-deprivation myopia, 030104 developmental biology, HEK293 Cells, chemistry, Alpha2a-adrenoceptor, Himbacine, Gene Knockdown Techniques, 030221 ophthalmology & optometry, Carbachol, Chickens, medicine.drug

الوصف: © 2018 The Authors. PURPOSE. Myopia is a refractive disorder that degrades vision. It can be treated with atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, but the mechanism is unknown. Atropine may block α-adrenoceptors at concentrations ≥0.1 mM, and another potent myopia-inhibiting ligand, mamba toxin-3 (MT3), binds equally well to human mAChR M 4 and α 1A -and α 2A -adrenoceptors. We hypothesized that mAChR antagonists could inhibit myopia via α 2A -adrenoceptors, rather than mAChR M 4 . METHODS. Human mAChR M 4 (M 4 ), chicken mAChR M 4 (cM 4 ), or human α 2A -adrenergic receptor (hADRA2A) clones were cotransfected with CRE/promoter-luciferase (CRE-Luc; agonist-induced luminescence) and Renilla luciferase (RLuc; normalizing control) into human cells. Inhibition of normalized agonist-induced luminescence by antagonists (ATR: atropine; MT3; HIM: himbacine; PRZ: pirenzepine; TRP: tropicamide; OXY: oxyphenonium; QNB: 3-quinuclidinyl benzilate; DIC: dicyclomine; MEP: mepenzolate) was measured using the Dual-Glo Luciferase Assay System. RESULTS. Relative inhibitory potencies of mAChR antagonists at mAChR M 4 /cM 4 , from most to least potent, were QNB > OXY ≥ ATR > MEP > HIM > DIC > PRZ > TRP. MT3 was 56☓ less potent at cM 4 than at M 4 . Relative potencies of mAChR antagonists at hADRA2A, from most to least potent, were MT3 > HIM > ATR > OXY > PRZ > TRP > QNB > MEP; DIC did not antagonize. CONCLUSIONS. Muscarinic antagonists block hADRA2A signaling at concentrations comparable to those used to inhibit chick myopia (≥0.1 mM) in vivo. Relative potencies at hADRA2A, but not M 4 /cM 4 , correlate with reported abilities to inhibit chick form-deprivation myopia. mAChR antagonists might inhibit myopia via α 2 -adrenoceptors, instead of through the mAChR M 4 /cM 4 receptor subtype.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c596f5c5f823bc2790d2c265817a823Test
https://pubmed.ncbi.nlm.nih.gov/29860464Test

المؤلفون: Luigino Calzetta, Mario Cazzola, Josuel Ora, Paola Rogliani, Maria Gabriella Matera

المساهمون: Rogliani, Paola, Ora, Josuel, Matera, Maria Gabriella, Cazzola, Mario, Calzetta, Luigino

مصطلحات موضوعية: LABA/LAMA FDC, Settore MED/10 - Malattie dell'Apparato Respiratorio, Bioinformatics, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Cardiovascular Disease, Drug Combination, Muscarinic acetylcholine receptor, Delayed-Action Preparation, Pharmacology (medical), 030212 general & internal medicine, Receptor, media_common, COPD, biology, Muscarinic acetylcholine receptor M2, General Medicine, Lama, Bronchodilator Agents, Muscarinic Antagonist, Drug Combinations, Cardiovascular Diseases, Drug, hormones, hormone substitutes, and hormone antagonists, Human, Adrenergic beta-2 Receptor Agonist, Chronic Obstructive, media_common.quotation_subject, LABA/LAMA FDCs, cardiovascular safety, Adrenergic beta-2 Receptor Agonists, Delayed-Action Preparations, Dose-Response Relationship, Drug, Humans, Muscarinic Antagonists, Dose-Response Relationship, Pulmonary Disease, 03 medical and health sciences, medicine, Adverse effect, Bronchodilator Agent, business.industry, medicine.disease, biology.organism_classification, Dual bronchodilation, 030228 respiratory system, business

الوصف: Introduction: Long-acting β2-adrenoceptor (β2-AR) agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) is the cornerstone for treating chronic obstructive pulmonary disease (COPD). LABA/LAMA combinations elicit clinical and functional synergistic interaction, and such an interaction should permit to reduce the dose of each monocomponent in the drug mixture to minimize the risk of adverse events (AEs). Overall, currently available LABA/LAMA fixed-dose combinations (FDCs) combine the drugs at the same doses of formulations designed for a single drug. Therefore, concerns regarding the possible risk of cardiovascular AEs have been raised related to the use of LABA/LAMA FDCs in COPD patients. Areas covered: LABAs and LAMAs have a high potential to induce cardiovascular AEs by stimulating the β2-AR receptors and inhibiting the muscarinic M2receptors expressed in the heart. This review will explore the data published on the cardiovascular safety of dual bronchodilation therapy in COPD patients. Expert opinion: LABA/LAMA FDCs are characterized by an acceptable cardiovascular safety profile, at least in the COPD population enrolled in randomized clinical trials. Nevertheless, large real life studies suggest that dual bronchodilation therapy may increase the risk of cardiovascular AEs. Post-marketing surveillance and observational studies are needed to adequately define the real cardiovascular safety profile of LABA/LAMA FDCs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6aff21ada85ba37c98962c3b639e0c4aTest
http://hdl.handle.net/2108/209474Test

المؤلفون: Misha F. Vrolijk, Ming Zhang, Guido R.M.M. Haenen

المساهمون: RS: NUTRIM - R3 - Respiratory & Age-related Health, Promovendi NTM, Farmacologie en Toxicologie, RS: CARIM - R2.03 - ECM + Wnt signaling

المصدر: International Journal of Molecular Sciences, Vol 19, Iss 1, p 18 (2017)
International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 19; Issue 1; Pages: 18
International journal of molecular sciences, 19(1):18. Multidisciplinary Digital Publishing Institute (MDPI)

مصطلحات موضوعية: 0301 basic medicine, Atropine, Male, anticholinergic accumulation, BLOOD, Traditional Chinese medicine, Pharmacology, Rats, Inbred WKY, lcsh:Chemistry, 0302 clinical medicine, EQUATION, Traditional Chinese Medicine, Receptors, Cholinergic, Medicine, Chinese Traditional, Receptor, lcsh:QH301-705.5, Spectroscopy, POPULATION, education.field_of_study, OUTCOMES, Chemistry, General Medicine, Risperidone, Computer Science Applications, RECEPTORS, RISK SCALES, Cimetidine, medicine.drug, medicine.drug_class, Population, Muscarinic Antagonists, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, ANTIOXIDANT CAPACITY, Theophylline, medicine, Anticholinergic, Journal Article, Total Atropine Equivalents, DRUGS, Animals, Humans, OLDER-PEOPLE, Physical and Theoretical Chemistry, education, Molecular Biology, Acetylcholine receptor, Ephedra sinica, Organic Chemistry, Pirenzepine, Rats, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, ASTHMA, 030217 neurology & neurosurgery, Drugs, Chinese Herbal

الوصف: Many Western drugs can give rise to serious side effects due to their ability to bind to acetylcholine receptors in the brain. This aggravates when they are combined, which is known as anticholinergic accumulation (AA). Some bioactives in Traditional Chinese Medicine (TCM) are known to block acetylcholine receptors and thus potentially cause AA. The AA of TCM was screened by quantifying the displacement of [3H] pirenzepine on acetylcholine receptors in a rat brain homogenate. We used a new unit to express AA, namely the Total Atropine Equivalents (TOAT). The TOAT of various herbs used in TCM was very diverse and even negative for some herbs. This is indicative for the broadness of the pallet of ingredients used in TCM. Three TCM formulas were screened for AA: Ma Huang Decotion (MHD), Antiasthma Simplified Herbal Medicine intervention (ASHMI), and Yu Ping Feng San (YPFS). The TOAT of ASHMI was indicative for an additive effect of herbs used in it. Nevertheless, it can be calculated that one dose of ASHMI is probably too low to cause AA. The TOAT of YPFS was practically zero. This points to a protective interaction of AA. Remarkably, MHD gave a negative TOAT, indicating that the binding to the acetylcholine receptors was increased, which also circumvents AA. In conclusion, our results indicate that TCM is not prone to give AA and support that there is an intricate interaction between the various bioactives in TCM to cure diseases with minimal side effects.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5a9cdddef36c96a5d2d0d4b3b2997ac6Test
https://www.mdpi.com/1422-0067/19/1/18Test