Progress in Medicinal Chemistry 24 This Page Intentionally Left Blank Progress in Medicinal Chemistry 24 Edited by G.P. ELLIS, D.SC., PH.D., F.R.S.C. Department of Applied Chemistry, University of Wales Institute of Science and Technology. P.O. Box 13, Cardiff. CF1 3XF, United Kingdom and G.B. WEST, B . PHARM., D.SC., PH.D., F.I.BIOL. Department of Paramedical Sciences, North East London Polytechnic, Romford Road, London, E l 5 4 L Z , United Kingdom 1987 ELSEVIER AMSTERDAM. NEW YORK .OXFORD 0 1987, Elsevier Science Publishers B.V. (Biomedical Division) 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, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher, Elsevier Science Publishers B.V. (Biomedical Division), P.O. Box 1527, 1000 BM Amsterdam, The Netherlands. No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of rapid advances in the medical sciences, the Publisher recommends that independent verification of diagnoses and drug dosages should be made. Special regulations for readers in the U.S.A.: This publication has been registered with the Copyright Clearance Center Inc. (CCC), Salem, Massachusetts. Information can be obtained from the CCC about conditions under which the photocopying of parts of this publication may be made in the USA. All other copyright questions, including photocopying outside of the USA, should be referred to the publisher. ISBN 0-444-80876-0 ISBN Series 0-7204-7400-0 Published by: Elsevier Science Publishers B.V. (Biomedical Division) P.O. Box 21 1 1000 AE Amsterdam The Netherlands Sole distributors for the USA and Canada: Elsevier Science Publishing Company, Inc. 52 Vanderbilt Avenue New York, NY 10017 USA Library of Congress Cataloging in Publication Data: Please refer to card number 62-27/2 for this series Printed in The Netherlands Preface We have pleasure in presenting eight reviews in this volume, all of which cover important advances in the chemistry and biology of medicinal products. In Chapter 1, the structure, synthesis and toxicity of ricin, a protein present in the endosperm cells of the seeds of the castor oil plant, are described and possible uses of this toxic agent in immunology as conjugates with antibodies are discussed. The biochemical and pharmacological evidence for the presence of functional histamine receptors in the mammalian central nervous system is set out in Chapter 2. Chapter 3 covers the chemical properties of molybdenumcontaining enzymes such as aldehyde oxidase and xanthine oxidase, although their physiological roles are by no means clear. Biologically active platinum complexes, which cross-link defined regions of DNA in cells, possess antitumour activity, and these are evaluated in Chapter 4. In Chapter 5 , the present status of the medicinal uses of Cannabis is discussed, particularly as two cannabinoids are now oficial drugs. The latest methods of treating insulin-resistant diabetic patients with hypoglycaemic agents which do not act by increasing insulin release are described in Chapter 6. Chapter 7 covers the mechanisms involved in the treatment and prophylaxis of angina pectoris and moderate hypertension by drugs which block the passage of calcium ions into and out of cells. Finally, in Chapter 8, the discovery of clinically useful inhibitors of aldose reductase, an enzyme involved in chronic diabetes, is described. We thank our authors for surveying the ever-widening literature