title: The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease.
abstract: Muscarinic receptor antagonists and β-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. Here we review the pharmacological rationale for their combination. Muscarinic receptors and β-adrenoceptors are physiological antagonists for smooth muscle tone in airways and bladder. Muscarinic agonism may attenuate β-adrenoceptor-mediated relaxation more than other contractile stimuli. Chronic treatment with one drug class may regulate expression of the target receptor but also that of the opposing receptor. Prejunctional β2-adrenoceptors can enhance neuronal acetylcholine release. Moreover, at least in the airways, muscarinic receptors and β-adrenoceptors are expressed in different locations, indicating that only a combined modulation of both systems may cause dilatation along the entire bronchial tree. While all of these factors contribute to a rationale for a combination of muscarinic receptor antagonists and β-adrenoceptor agonists, the full value of such combination as compared to monotherapy can only be determined in clinical studies.
authors.affiliation: Department of Pharmacology, Cambridge University, Cambridge, UK.
authors.forename: Philippa R
authors.initials: PR
authors.lastname: Dale
authors.affiliation: University of Groningen, Department of Molecular Pharmacology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, GRIAC, Groningen, The Netherlands.
authors.forename: Hana
authors.initials: H
authors.lastname: Cernecka
authors.affiliation: University of Groningen, Department of Molecular Pharmacology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, GRIAC, Groningen, The Netherlands.
authors.forename: Martina
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Molecular Pharmacology, Respiratory Diseases, Novartis Institutes for Biomedical Research, Horsham, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Dowling
authors.affiliation: Department of Molecular Pharmacology, Respiratory Diseases, Novartis Institutes for Biomedical Research, Horsham, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Charlton
authors.affiliation: Respiratory Diseases Research and Department of Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH, Ingelheim, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Pieper
authors.affiliation: Respiratory Diseases Research and Department of Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH, Ingelheim, Germany; Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany. Electronic address: marmiche@uni-mainz.de.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004359:Drug Therapy, Combination; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D001745:Urinary Bladder Diseases / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D018727:Muscarinic Antagonists; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic