Muscarinic receptor antagonists and β-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. β2-adrenoceptors can enhance neuronal acetylcholine release. Moreover at least in the airways muscarinic receptors and Salinomycin (Procoxacin) 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 decided in clinical studies. Current Opinion in Pharmacology 2014 16 This review comes from a themed issue on Respiratory Edited by Julia K L Walker and John T Fisher For a complete overview see the Issue Rabbit polyclonal to PFKFB3. and the Editorial Available online 27th March 2014 1471 – see front matter ? 2014 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.coph.2014.03.003 Introduction Obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) and urinary bladder dysfunction such as the overactive bladder syndrome (OAB) are Salinomycin (Procoxacin) typically seen as unrelated conditions. However both affect hollow organs and are characterized by an imbalance between contractile and relaxant easy muscle stimuli. Moreover the sympathetic and the parasympathetic nervous system plays important functions in both cases although sympathetic innervation may be sparse [1]; accordingly muscarinic receptor antagonists and β-adrenoceptor agonists are important therapeutics Salinomycin (Procoxacin) for both organ systems. The present manuscript reviews the molecular cellular and tissue rationale underlying the combined use of these two drug classes. We combine data from airways and urinary bladder to improve the robustness of emerging concepts. Clinical background COPD is usually a progressive disease associated mainly with tobacco smoking air pollution or occupational exposure which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. Inhaled bronchodilators (β2 adrenoceptor agonists or M3 muscarinic acetylcholine receptor antagonists) remain the mainstay of current management of COPD at all stages of the disease [2??]. Clinical advances in the treatment of COPD have centered on improvements of these existing classes of bronchodilators Salinomycin (Procoxacin) by either increasing duration of action or by improving their selectivity profiles [2??]. The combination of a β2-adrenoceptor agonist with a M3 muscarinic receptor antagonist into a fixed-dose combination therapy Salinomycin (Procoxacin) is currently being pursued by several pharmaceutical companies. The Global Initiative For Asthma defines asthma as a ‘chronic inflammatory disorder of the airways in which many cells and cellular elements play a role’ (www.ginasthma.org). In bronchi from asthmatic patients contraction responses to muscarinic receptor agonists are enhanced and relaxation responses to β-adrenoceptor agonists are attenuated [3]. This airway hyperresponsiveness leads to recurrent episodes of wheezing breathlessness chest tightness and coughing particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment. First-line treatment of asthma is based on low-to-medium doses of an inhaled glucocorticoid but this yields inadequate symptom control in many patients. Short-acting muscarinic receptor antagonists and β-adrenoceptor agonists often in combination can be added as acute reliever medication. Long-acting β-adrenoceptor agonists are an option as additional controllers but their safety when used as monotherapy has been questioned. Alternative/additional controller medications are needed [4] and the combination of a long-acting β-adrenoceptor agonist with a long-acting muscarinic antagonist is considered a possible option. However the efficacy and safety of such a combination or of monotherapy with a long-acting muscarinic antagonist has not been fully evaluated and hence is not an approved use. OAB is defined by the International Continence Society by the presence of urgency with or without incontinence usually accompanied by urinary frequency and nocturia [5]. For a long time muscarinic receptor antagonists have been the mainstay of OAB treatment [6] but recently β3-adrenoceptor agonists are emerging as an alternative treatment option [7? 8 the combined use of.