Friedrich Kummer (ed.) Treatment of Asthma: The long-acting beta-2-agonists. Springer WienN ewyork

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2 Friedrich Kummer (ed.) Treatment of Asthma: The long-acting beta-2-agonists Springer WienN ewyork

3 Prof. Dr. med. Friedrich Kummer 2. Medizinische Abteilung mit Lungenkrankheiten und Tuberkulose, Wilhelminenspital, Wien, Osterreich This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machines or similar means, and storage in data banks. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of specific statements that such names are exempt from the relevant protective laws and regulations and therefore free for general use Springer-VerlaglWien Typesetting: H. Meszarics Satz & Layout A-1200 Wien Graphic design: Ecke Bonk Printed on acid-free and chlorine-free bleached paper SPIN: With 35 Figures Library of Congress Cataloging-in-Publication Data Treatment of asthma: the long-acting beta-2-agonists / Friedrich Kummer (Hrsg.) p.cm. Includes bibliographical references and index. ISBN -l3: l24-3 e-isbn -l3: l3-2 DOl: / l Asthma - Chemotherapy. 2. Adrenergic beta agonists. I. Kummer, Friedrich. [DNLM: I. Asthma - drug therapy.,2. Adrenergic beta-agonists - therapeutic use. 3. Adrenergic beta-agonists - pharmacology. WF 553 T ] RC591.T ' dc21 ISBN -13 :

4 Preface The traditional Vienna Asthma Forum was held in early June 1996 and was the 6th in a biennial mode within 10 years. This time it was dedicated to the long-acting beta-2-agonists, which were registered (or just about to be) in most European countries. The introduction of this therapeutic principle into routine praxis of asthma therapy was so successful that a closer view on the subject from a scientific point was warranted. Salmeterol, shortly afterwards formoterol are the drugs available for the inhalative route, while bambuterol serves as an oral agent. The scientists particularly involved in the design and pharmacokinetics of these drugs were invited, and we were lucky that Malcolm Johnson (Glaxo), Leif Svensson (Astra) and Gary Anderson (Ciba Geigy) delivered fascinating contributions. However, drug therapy of this kind can only be effective if based on a thorough understanding of the molecular biology of cells and receptors, which was superbly covered by Sheila Collins (Durham) and Ian M. Adcock (London). The pediatric indications for beta-2-agonists were commented by Manfred G6tz (Vienna), and a large spectrum of clinical studies, reported by G. Boyd (Glasgow), A.P. Greening (Edinburgh), M. Rudolph (Middlesex), O. Selroos (Lund) and B. Villiger (Davos) evoked the mutual acid interest of speakers and audience, who engaged in vivid, high quality discussions. The clinical round up and outlook to the future was contributed by Leo Fabbri (Ferrara), who - as an important representative of the European School of Respiratory Medicine - gave the touch of the European Respiratory Society to the entire meeting.

5 VI Preface We were keen to include the complete discussion into the proceedings mediating the lively spirit and intense interest of all participants. Vienna, May 1998 Univ.-Prof Dr. F. Kummer

6 Contents Contributors... Collins, s., Wang, S.: Molecular regulation of the P2-adrenergic receptor by long- and short-acting p-agonists... 1 Adcock, I.M., Stevens, D.A.: Molecular interactions between glucocorticoids and pz-agonists Anderson, G.: Formoterol, a new long-acting P2-agonist Johnson, M.: Development of the long-acting P2-agonist, salmeterol Svensson, L.-A.: Development ofbambuterol; a long acting, orally active beta-agonist prodrug G6tz, M.: Development of pz-receptors in infancy and childhood Villiger, B.: Long-acting beta-agonists in exercise induced asthma Boyd, G.: Salmeterol and oral steroid treatment Greening, AP.: Salmeterol and its relationship to treatment with inhaled corticosteroids Rudolf, M.: Long term treatment with formoterol Selroos, 0.: Comparison of efficiency of bambuterol and salmeterol Papi, A, Beghe, B., Caramori, G., Ciaccia, A Fabbri, L.M.: The future of relievers and controllers in asthma therapy IX

7 Contributors Dr. Ian M. Adcock, Department of Thoracic Medicine, Imperial College School of Medicine at NHU, London, U. K. Dr. Gary Anderson, Department of Pharmacology, University of Melbourne, Australia Dr. Gavin Boyd, Consultant Respiratory Physician, Stobhill Hospital, Glasgow, U.K. Dr. Sheila Collins, Duke University Medical Center, Division of Biological Psychiatry and Pharmacology, S.W. Stedman Center for Nutritional Studies, Durham, North Carolina, U.S.A. Alberto Papi, Laboratorio di Ricerca sull' Asma Bronchiale, Azienda Ospedaliera S. Anna, 3 Piano Nuove Clinic he, Ferrara, Italy Manfred Gatz, M.D., Professor of Paediatrics, Head, Department of Paediatric and Adolescent Medicine, Wilhelminenspital, Vienna, Austria Dr. Andrew Greening, Consultant Physician, Respiratory Medicine Clinic, Western General Hospital, Edinburgh, U. K. Dr. Malcolm Johnson, Glaxo Wellcome Research & Development, Uxbridge, Middlesex, U.K. Dr. Michael Rudolf, Department of Respiratory Medicine, Ealing Hospital, Southall Middlesex, U.K. Prof Dr. Olof Selroos, Lund, Sweden Prof Dr. Leif-Ake Svensson, Department of Medicinal Chemistry, Astra Draco AB, Lund, Sweden Dr. Beat Villiger, Swiss Olympic Medical Center, Sportmed SO, Davos Platz, Switzerland