Search results for "Muscarinic Antagonist"
showing 10 items of 90 documents
Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isol…
2018
[EN] A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1 mu M), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activatio…
Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M3 Receptor Antagonist/β2-Adrenoceptor Agonist Molecule with Long-Lasting Effect…
2019
AZD8871 is a novel muscarinic antagonist and β2-adrenoceptor agonist in development for chronic obstructive pulmonary disease. This study describes the pharmacological profile of AZD8871 in in vitro and in vivo assays. AZD8871 is potent at the human M3 receptor (pIC50 in binding assays: 9.5) and shows kinetic selectivity for the M3 (half-life: 4.97 hours) over the M2 receptor (half-life: 0.46 hour). It is selective for the β2-adrenoceptor over the β1 and β3 subtypes (3- and 6-fold, respectively) and shows dual antimuscarinic and β2-adrenoceptor functional activity in isolated guinea pig tissue (pIC50 in electrically stimulated trachea: 8.6; pEC50 in spontaneous tone isolated trachea: 8.8, r…
Pharmacological preclinical characterization of LAS190792, a novel inhaled bifunctional muscarinic receptor antagonist /β 2 -adrenoceptor agonist (MA…
2017
LAS190792 is a novel muscarinic antagonist and β2-adrenoceptor agonist in development for chronic respiratory diseases. This study investigated the pharmacological profile of LAS190792 in comparison to batefenterol, tiotropium, indacaterol and olodaterol. LAS190792 is potent at the human M3 receptor (pIC50: 8.8 in binding assays). It is selective for the β2-adrenoceptor over the β1-and β3-adrenoceptor, and shows a functional potency in a similar range to batefenterol and LABA compounds (pEC50 in spontaneous tone isolated trachea: 9.6). The relaxant potency of LAS190792 in electrically stimulated tissue is similar to batefenterol, with an antimuscarinic activity in presence of propranolol sl…
Symptom variability and control in COPD: Advantages of dual bronchodilation therapy
2017
Abstract Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder characterized by usually progressive development of airflow obstruction that is not fully reversible. While most patients will experience symptoms throughout the day or in the morning upon awakening, many patients do not experience their symptoms as constant but report variability in symptoms during the course of the day or over time. Symptom variability adversely affects patients' health status and increases the risk of COPD exacerbations. Methods We examined data from the literature on symptom variability and control in patients with COPD, with focus on the use of inhaled bronchodilator therapy wi…
Early management of COPD: Where are we now and where do we go from here? a delphi consensus project
2019
Fabiano Di Marco,1 Piero Balbo,2 Francesco de Blasio,3 Vittorio Cardaci,4 Nunzio Crimi,5 Giuseppe Girbino,6 Girolamo Pelaia,7 Pietro Pirina,8 Pietro Roversi,9 Pierachille Santus,10,11 Nicola Scichilone,12 Alessandro Vatrella,13 Patrizio Pasqualetti,14 Mauro Carone15 1Department of Health Sciences, University of Milan, Respiratory Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy; 2SC Malattie dell’Apparato Respiratorio, AOU Maggiore della Carità, Novara, Italy; 3Respiratory Medicine and Pulmonary Rehabilitation Section, Clinic Center S.p.A. Private Hospital, Department of Medicine and Health Sciences “V Tiberio”, University of Molise, Campobasso, It…
Nonlinear coupling is absent in acute myocardial patients but not healthy subjects.
2008
We investigated whether autonomic nervous system imbalance imposed by pharmacological blockades and associated with acute myocardial infarction (AMI) is manifested as modifications of the nonlinear interactions in heart rate variability signal using a statistically based bispectrum method. The statistically based bispectrum method is an ideal approach for identifying nonlinear couplings in a system and overcomes the previous limitation of determining in an ad hoc way the presence of such interactions. Using the improved bispectrum method, we found significant nonlinear interactions in healthy young subjects, which were abolished by the administration of atropine but were still present afte…
Intoxication with a tropenol ester.
2012
BACKGROUND While the effects of medicinal products are investigated in depth before approval, often very little is known about the intermediates occurring during synthesis. The pharmacological properties of these intermediates can differ substantially from those of the end product. AIMS To describe a work accident involving intoxication with such an intermediate, tropenol ester. CASE REPORT A healthy 40-year-old chemical-technical operative erroneously used a scrubbing brush that had just been used to clear up tropenol ester, contaminating his work clothes. Presumably, contact was made with his skin when removing his work clothes later. Shortly thereafter, he developed signs of anticholiner…
Glycopyrronium bromide blocks differentially responses mediated by muscarinic receptor subtypes.
1993
To analyse the potency of glycopyrronium bromide in blocking responses mediated via subtypes of muscarinic receptors in vitro, we tried to determine its equilibrium dissociation constants at prejunctional muscarinic receptors inhibiting the twitch response of rabbit vas deferens (presumed M1 type), at M2 (paced at left atria), M3 (guinea pig ileum) muscarinic receptor subtypes and at the muscarinic receptor of the rabbit iris sphincter (not M1-M4, not m5). Glycopyrronium bromide shifted to the right the curve for inhibition of the twitch response induced by the agonist McN-A-343, and the methacholine-induced curves for inhibition of rat atrial contraction, and for tonic contraction of guine…
Role for NK1 and NK2 receptors in the motor activity in mouse colon
2007
The present study examined the effects induced by endogenous and exogenous activation of NK(1) and NK(2) receptors on the mechanical activity of mouse proximal colon. Experiments were performed in vitro recording the changes in intraluminal pressure from isolated colonic segments. Electrical field stimulation in the presence of atropine and guanethidine produced a small relaxation, followed by nonadrenergic noncholinergic (NANC) contraction. SR140333, NK(1) receptor antagonist, or SR48968, NK(2) receptor antagonist, significantly reduced the contraction, although SR48968 appeared more efficacious. The co-administration of SR140333 and SR48968 virtually abolished the NANC contraction. [Sar(9…
Involvement of purinergic nerves in the NANC inhibitory junction potentials in pigeon oesophageal smooth muscle.
2004
1. Electrical field stimulation (EFS) (0.5 ms in train of 2-32 Hz for 300 ms) in smooth muscle of pigeon oesophagus, in the presence of atropine (1 microm) and guanethidine (1 microm), elicited an inhibitory response consisting of a transient hyperpolarization (inhibitory junction potential, IJP) associated with muscle relaxation. 2. Sodium nitroprusside (SNP, 100 microm) induced hyperpolarization correlated to mechanical relaxation. 3. The nitric oxide (NO) synthase inhibitor N(omega)-nitro-l-arginine (from 0.1 to 100 microm) caused a concentration-dependent reduction of electromechanical response to EFS indicating a role for NO in this response. 4. Apamin (1 microm) reduced both IJP and r…