Search results for "Musca"
showing 10 items of 300 documents
S61 Analysis of the efficacy and safety of the combination of tiotropium + olodaterol in patients with COPD by previous usage of inhaled corticostero…
2015
Rationale Tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist (both administered once daily), have been studied as a once-daily combination. Two Phase III studies have demonstrated that T+O significantly improved lung function and symptoms over T and O monotherapy treatments in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). 1 During these studies, patients were allowed to continue existing treatment with inhaled corticosteroids (ICS); this analysis was conducted to determine the effects of study treatment in patients receiving or not receiving ICS as reported at baseline. Methods A total of 5162 patients we…
Aclidinium inhibits human lung fibroblast to myofibroblast transition
2011
Background Fibroblast to myofibroblast transition is believed to contribute to airway remodelling in lung diseases such as asthma and chronic obstructive pulmonary disease. This study examines the role of aclidinium, a new long-acting muscarinic antagonist, on human fibroblast to myofibroblast transition. Methods Human bronchial fibroblasts were stimulated with carbachol (10 −8 to 10 −5 M) or transforming growth factor-β1 (TGF-β1; 2 ng/ml) in the presence or absence of aclidinium (10 −9 to 10 −7 M) or different drug modulators for 48 h. Characterisation of myofibroblasts was performed by analysis of collagen type I and α-smooth muscle actin (α-SMA) mRNA and protein expression as well as α…
Impact of long-term treatment with inhaled corticosteroids and bronchodilators on lung function in a patient with post-infectious bronchiolitis oblit…
2016
Post-infectious bronchiolitis obliterans (PIBO) is a small airways disease characterized by fixed airflow limitation. Therefore, inhaled bronchodilators and corticosteroids are not recommended as maintenance therapy options. The management of PIBO currently consists only of close monitoring of affected patients, aimed at the prevention and early treatment of pulmonary infections. In recent years, there has been an increase in the incidence of PIBO in the pediatric population. Patients with PIBO are characterized by a progressive decline in lung function, accompanied by a decrease in overall functional capacity. Here, we report the case of a relatively young man diagnosed with PIBO and follo…
Muscarinic M2 receptors in acetylcholine-isoproterenol functional antagonism in human isolated bronchus
2002
The muscarinic functional antagonism of isoproterenol relaxation and the contribution of muscarinic M2 receptors were examined in human isolated bronchus. In intact tissues, acetylcholine (ACh) precontraction decreased isoproterenol potency and maximal relaxation (−log EC50 shift = −1.49 ± 0.16 and Emax inhibition for 100 μM ACh = 30%) more than the same levels of histamine contraction. The M2receptor-selective antagonist methoctramine (1 μM) reduced this antagonism in ACh- but not histamine-contracted tissues. Similar results were obtained for forskolin-induced relaxation. After selective inactivation of M3 receptors with 4-diphenylacetoxy- N-(2-chloroethyl)piperadine hydrochloric acid (3…
One-year follow up of asthmatic patients newly initiated on treatment with medium- or high-dose inhaled corticosteroid-long-acting β2-agonist in UK p…
2020
Abstract Introduction Global Initiative for Asthma (GINA) recommends medium- or high-dose inhaled corticosteroid-long-acting β2-agonist (ICS-LABA) as preferred treatments for patients with moderate-to-severe asthma. Limited data is available on how step 4/5 patients respond to ICS-LABA and how they step up/down in clinical practice. Methods This retrospective cohort study assessed the characteristics, control status, treatment pathways, and healthcare resource utilization in patients with asthma during one year after initiating medium- or high-dose ICS-LABA. Data from the United Kingdom Clinical Practice Research Datalink were analysed between January 01, 2006 and February 28, 2016. Results…
Indacaterol/glycopyrronium/mometasone fixed dose combination for uncontrolled asthma
2021
INTRODUCTION Asthma symptoms can be relieved through a maintenance treatment combining long-acting β2-agonist and inhaled corticosteroids (LABA/ICS). However, for patients with inadequately controlled asthma, the LABA/ICS combination might not be sufficient. Under these conditions, clinical guidelines recommend the administration of inhaled long-acting muscarinic antagonists (LAMA) as an add-on therapy to LABA/ICS to better control asthma and improve lung function. For nearly two decades, the only LAMA to be approved on the market has been tiotropium. AREAS COVERED We reviewed recent clinical studies evaluating the safety and efficacy of LABA/LAMA/ICS fixed dose combinations by searching Pu…
Design and pharmacology of quinuclidine derivatives as M2-selective muscarinic receptor ligands
2001
In our search for M2-selective muscarinic receptor antagonists, we synthesized 1,3-disubstituted indenes. The effects of different basic moieties with regard to binding and selectivity towards the five distinct muscarinic receptor subtypes were investigated. The results show that the quinuclidine series afforded the most promising compounds in terms of both receptor affinity and M2-subtype selectivity.
The Concise Guide To Pharmacology 2021/22: G Protein-Coupled Receptors
2021
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will s…
Conformational Isomerism in Drug Action: Does the Free Energy of Binding Induce the Pharmacophoric Conformation of Semi-Rigid Muscarinic Agonists?
1974
The physiological neurotransmitter Acetylcholine has been shown to have great molecular flexibility, and because of this, the possibility of forming numerous energetically different conformations. This property makes the determination of the biologically active conformation extremely complicated. In attempts to solve this problem various research groups have tried two basically different approaches: (1) (1) The determination of the energetically most stable conformation using crystallographic methods (X-ray diffraction studies), nuclear magnetic resonance and quantum-mechanical calculations [1–16]. Same workers hypothesized that the energetically most favourable form was also the biological…
The effects of metoclopramide on acetylcholine release and on smooth muscle response in the isolated guinea-pig ileum
1982
The effects of metoclopramide on smooth muscle contraction and on release of acetylcholine were studied in the guinea-pig myenteric plexus longitudinal muscle preparation. Acetylcholine was determined either as endogenous acetylcholine, or as labelled transmitter from strips preloaded with 3H-choline. Metoclopramide caused an increase in resting tension of longitudinal muscle as well as an increase in resting output of either endogenous or labelled acetylcholine. Tetrodotoxin abolished the metoclopramide-evoked increase in transmitter release. The increase in smooth muscle tension was clearly related to the increase in resting output. The effects of metoclopramide on both longitudinal muscl…