Monoamine Oxidases and their Selective Inhibition. Proceedings of the 3rd Congress of the Hungarian Pharmacological Society, Budapest, 1979 PDF
Preview Monoamine Oxidases and their Selective Inhibition. Proceedings of the 3rd Congress of the Hungarian Pharmacological Society, Budapest, 1979
ADVANCES IN PHARMACOLOGICAL RESEARCH AND PRACTICE Proceedings of the 3rd Congress of the Hungarian Pharmacological Society; Budapest, 1979 General Editor: J. KNOLL, Budapest Volumes and Editors: I - PHARMACOLOGICAL CONTROL OF HEART AND CIRCULATION. Editors: L. Tardos, L. Szekercs and J. Gy. Papp II - MODULATION OF NEUROCHEMICAL TRANSMISSION. Editor: E. S. Vizi III - CHEMICAL STRUCTURE-BIOLOGICAL ACTIVITY RELATIONSHIPS. QUANTITATIVE APPROACHES. Editor: F. Darvas IV - MONOAMINE OXIDASES AND THEIR SELECTIVE INHIBITION. Editor: K. Magyar V - OPIATE RECEPTORS AND THE NEUROCHEMICAL CORRELATES OF PAIN. Editor: Susanna Furst VI - PROSTANOIDS. Editor: Valeria Kecskem&i {Each volume is available separately.) Satellite Symposium of the 3rd Congress of the Hungarian Pharmacological Society, Szeged, Hungary, 1979 VII - AMINERGIC AND PEPTIDERGIC RECEPTORS. Editors: E. S. Vizi and Maria Wollemann ADVANCES IN PHARMACOLOGICAL RESEARCH AND PRACTICE Proceedings of the 3rd Congress of the Hungarian Pharmacological Society, Budapest, 1979 Volume IV MONOAMINE OXIDASES AND THEIR SELECTIVE INHIBITION Editor: K. MAGYAR Department of Pharmacology Semmelweis University of Medicine Budapest, Hungary miiiiim PERGAMON PRESS AKADEMIAI K I A D6 Pergamon Press is the sole distributor for all countries, with the exception of the socialist countries. HUNGARY Akademiai Kiadd, Budapest, Alkotmany u. 21. 1054 Hungary U.K. Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 0BW, England U.S.A. Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, New York 10523, U.S.A. CANADA Pergamon of Canada, Suite 104,150 Consumers Road, Willowdale, Ontario M2 J1P9, Canada AUSTRALIA Pergamon Press (Aust.) Pty. Ltd., P.O. Box 544, Potts Point, N.S.W. 2011, Australia FRANCE Pergamon Press SARL, 24 rue des Ecoles, 75240 Paris, Cedex 05, France FEDERAL REPUBLIC Pergamon Press GmbH, 6242 Kronberg-Taunus, OF GERMANY Hammerweg 6, Federal Republic of Germany Copyright © Akademiai Kiad6, Budapest 1980 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic tape, mechanical, photocopy- ing, recording or otherwise, without permission in writing from the publishers. British Library Cataloguing in Publication Data Monoamine oxidases and their selective inhibition. — (Advances in pharmacological research and practice, Vol. IV). 1. Monoamine oxidase inhibitors — Congresses I. Magyar, K II. Hungarian Pharmacological Society. Congress, 3rd, Budapest, 1979 III. Series 615'.78 QP603.M6 80-41281 Pergamon Press ISBN 0-08-026389-5 ISBN 0-08-026385-2 (7 Vol set) Akademiai Kiado ISBN 963 05 2490 2 (Volume IV) ISBN 963 05 2367 1 (7 Vol set) In order to make this volume available as economical- ly and as rapidly as possible the authors* typescripts have been reproduced in their original forms. This method unfortunately has its typographical limita- tions but it is hoped that they in no way distract the reader. Printed in Hungary PREFACE The discovery of the selective monoamine oxidase (MAO) inhibitors, like clorgyline and deprenyl, has given a new impetus to MAO research as well as to the clinical ap- plicability of these compounds. Clorgyline, preferentially a MAO-A inhibitor, me- tabolises mainly serotonin, whereas deprenyl, the selective inhibitor of MAO-Bris re- sponsible for the deamination of phenylethylamine. Recent research on deprenyl has promoted its usefulness in Parkinson's disease. Its wider application has deepened our understanding about the dopaminergic mechanism that is responsible for the patho- logical process. This volume contains 21 papers by researchers and clinicians from 8 different coun- tries. The topic is first approached by reports on the pharmacological effects and the biochemical mode of actions of deprenyl and some other new selective inhibitors, then by communications concerning the biochemical methods applied in the study of the nature of MAO in the mitochondrial membrane. Finally, the neurologists give an account of their experience with the clinical application of deprenyl, and other in- hibitors in Parkinsonian patients, discussing also the essential role of the dopaminergic mechanism with respect to the disease. K. Magyar VII LIST OF CONTRIBUTORS Antal, J. Department of Neurology, Semmelweis University of Medicine, Buda- pest, Hungary Ask, Anna-Lena Research and Development Laboratories, Astra Lakemedel AB, S-151 85 Sodertalje, Sweden Bernath, G. Institute of Pharmaceutical Chemistry, University Medical School, Szeged, Hungary Birkmayer, W. Evangelisches Krankenhaus, 1090 Vienna, Austria Blaschko, H. University Department of Pharmacology, South Parks Road, Oxford 0X1 3QT, U. K. Csanda, E. Department of Neurology, Semmelweis University of Medicine, Buda- pest, Hungary Ecseri, Z. CHINOIN Pharmaceutical and Chemical Works, Budapest, Hungary Egashira, T. Department of Pharmacology, Showa University, School of Medicine, Hatanodai 1-5-8, Shingawa-Ku, Tokyo, Japan Ekstedt, B. Department of Pharmacology, University of Umea S-901 87, Umea, Sweden Fornadi, F. Department of Neurology, Semmelweis University of Medicine, Buda- pest, Hungary Fowler, C. J. Department of Pharmacology, University of Umea, S-901 87, Umea, Sweden Grahovska, T. Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria Harsing, L. G., Jr. Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Jellinger, K. Ludwig Boltzmann Institute for Clinical Neurobiology, A-l 130 Vienna, Austria Kalasz, H. Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Kenney, W, C. Molecular Biology Division, Veterans Administration Medical Center, San Francisco, CA, U.S.A. Kerecsen, L. Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Kinemuchi, H. Department of Pharmacology, Showa University, School of Medicine, Hatanodai 1-5-8, Shingawa-Ku, Tokyo, Japan Knoll, Bertha Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Knoll, J. Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Magyar, K. Department of Pharmacodynamics, Semmelweis University of Medi- cine, Budapest, Hungary IX Mashkovsky, M. D. All-Union Chemical-Pharmaceutical Research Institute, Moscow, U.S.S.R. Molnar, Gy. Department of Psychiatry, Semmelweis University of Medicine, Buda- pest, Hungary Nagy, J. Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Oreland, L. Department of Pharmacology, University of Umea, S-901 87, Umea, Sweden Paech, C. Molecular Biology Division, Veterans Administration Medical Center, San Francisco, CA, U.S.A. Rausch, W. D. Ludwig Boltzmann Institute for Clinical Neurobiology, Lainz Hospital, A-l 130 Vienna, Austria Reynolds, G. P. Ludwig Boltzmann Institute for Clinical Neurobiology, A-l 130 Vienna, Austria Riederer, P. Ludwig Boltzmann Institute for Clinical Neurobiology, Lainz Hospital, A-l 130 Vienna, Austria Rinne, U. K. Department of Neurology, University of Turku, SF-20520 Turku 52, Finland Ross, S. B. Research and Development Laboratories, Astra Lakemedel AB, S-151 85 Sodertalje, Sweden Salach, J. I. Molecular Biology Division, Veterans Administration Medical Center, San Francisco, CA, U.S.A. Sandler, M. Bernhard Baron Memorial Research Laboratories and Institute of Ob- stetrics and Gynaecology, Queen Charlotte's Maternity Hospital, Lon- don W6 OXG, U.K. Satory, Eva Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Singer, T. P. Molecular Biolpgy Division, Veterans Administration Medical Center, San Francisco, CA, U.S.A. Tekes, Kornelia Department of Pharmacodynamics, Semmelweis University of Medi- cine, Budapest, Hungary Vizi, E. S. Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary Wajsbort, J. Department of Neurology, Linn Clinic, Haifa, Israel Yahr, M. D. Department of Neurology, Mt. Sinai School of Medicine, 100th Street at 5th Avenue, New York, N.Y. 10029, U.S.A. Yanev, S. Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria Youdim, M, B, H. Department of Pharmacology, Technion Israel Institute of Technology, Haifa, Israel X Third Congress of the Hungarian Pharmacological Society, Budapest 1979 THE ANALYSIS OF AMINE OXIDASES BY THE USE OF ENZYME INHIBITORS Introductory Remarks H. Blaschko University Department of Pharmacology South Parks Road, Oxford 0X1 3QT, U.K. The early work on the classification of the amine oxidases owes much to the use of enzyme inhibitors. It was established in the nineteen thirties that neither cyanide nor semicarbazine inhibited monoamine oxidase /MAO/ but that histaminase /or diamine oxidase/ was inhibited by these substances. On the other hand, ephedrine or amphetamine were found to be competitive inhibitors of MAO. Also, MAO was shown to differ from diamine oxidase /histaminase/ by attacking both primary and secondary amines, e.g. adrenaline and noradrenaline. More recently, enzyme inhibitors have proved useful in the characterization of enzymes oxidizing histamine and its N-methylated derivatives in both invertebrates and verte- brates. Two examples may illustrate this. 1. It was known for some time that the tissues of Cephalopods are very rich in MAO. When Dr. Margaret Boadle /1969/ examined the tissues of Eledone Cirrhosa, an octopod species, she confirmed earlier findings but she also dis- covered that homogenates of renal appendages, a tissue not 1 studied previously, oxidized among other amines also hist- amine. This observation was futher analysed. It was found that the oxidation of histamine by homogenates of the renal appendages was insensitive to semicarbazide. Dr. Boadle then tested the omega-N-methylated derivative of histamine, that in which the side-chain N atom is methylated. This compound is not attacked by the classical histaminase. How- ever, it was readily oxidized by the renal appendages. Dr. Boadle concluded that here the histamine was not oxidized by a histaminase-type of catalyst but by a special kind of MAO. It would be of interest to extend these observations and to find out, with the help of clorgyline and deprenyl, which form of MAO is responsible for the action on histamine. 2. For a long time it has been known that another N-methylated histamine derivative is an important metabolite of histamine in mammals; this l-methyl-4(3-aminoethyl) - imidazole is also called tele-methylhistamine /t-MH/. This compound has the methyl group on one of the ring nitrogen atoms. It has also long been known that t-MH is a substrate of MAO. The presence of t-MH in the brain of mammals has been studied. Upon incubation of brain homogenates, t-MH was found to be oxidized /Huogh and Domino, 1979/ ; the oxidation was very sensitive to deprenyl and relaively insensitive to clorgyline. The authors take these findings as indication that t-MH is a substrate of the type B form of MAO in the mammalian brain. These two sets of observations may serve as examples for the usefulness of enzyme inhbitors in the study of the 2 catabolism of biogenic amines. Histamine may be a little unconventional and unexpected in this context, but these results show that new findings may be brought to light by careful analysis. References Boadle, M. C. /1969/. Observations on a histaminase of invertebrate origin : A contribution to the study of cephalopod amine oxidases. Comp. Biochem. Physiol., 30, 611 - 620 . Huogh, L. B., and Domino, E. F. /1979/. Tele-methylhistam- ine oxidation by Type B monoamine oxidase. J. Pharmacol. Exp. Ther. 208, 422 - 428 . 3 Third Congress of the Hungarian Pharmacological Society, Budapest 1979 RECENT CLINICAL STUDIES IN MONOAMINE OXIDASE INHIBITION M.Sandler Bernhard Baron Memorial Research Laboratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital London W6 OXG, U.K. It has always been assumed that any therapeutic benefit achieved from using monoamine oxidase (MAO) inhibitors in depressive illness stems from a central accumulation of one or more monoamines. This may be, but the particular amine or amines responsible have not so far been identified. Johnston's (1968) classification of the enzyme into A and B forms, with their separate substrate and inhibitor specificities, makes it possible to some extent to narrow down the MAO substrates likely to be involved and indeed, recent evidence has been put forward to suggest that MAO A inhi- bitors are potentially better antidepressants than those of MAO B (Lipper et al.9 1979). To what extent "fine-tuning" mechanisms exist to regulate MAO activity in vivo is still unknown. Progesterone administration, at least, has been shown to lead to an increased activity of endometrial MAO A (Mazumder et aZ.^1979). Very recently, the question of the existence of endogenous MAO inhibitors has been mooted for the first time. Endogenous MAO inhibitors? Berrettini & Vogel (1978) recently claimed to find a small molecule inhibitor in the plasma of certain schizophrenic patients with low platelet MAO activity. If a small molecule inhibitor of this type were to exist as a physiological phenomenon, the obvious place to look for it would be the urine. Using a crude rat liver homogenate as enzyme source and, later, a human platelet preparation, we have been able to demonstrate a substantial inhibitory action of human urine (Glover et al., 1979). Although individual urinary constituents such as urea (Giordano et al. 3 1962) are known to possess some degree of competitive inhibitory activity in high concentration, it soon became obvious that we were seeking some- thing more specific. A simulated urine sample reconstituted from a 5
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