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All Rights Reserved No part of this book may be reproduced in any form by photostat, microfilm, or any other means, without written permission from the pubhshers Library of Congress Catalog Number: 63-22091 PRINTED IN GREAT BRITAIN BY SPOTTISWOODE, BALLANTYNE AND CO. LTD LONDON AND COLCHESTER University as a post-doctoral fellow. It is a great pleasure for me to express my indebtedness to Professor C. H. Waddington for his encouragement in the pursuit of a theoretical study of biological processes, and for reading and suggesting improvements in the manuscript, I would like also to thank Dr. H. Kacser for discussions which clarified the groundwork of this analysis. In addition I owe a debt of gratitude to friends at the Massachusetts Institute of Technology who read and criticized various parts of the manuscript, especially Karl Kornacker. Finally it is to the National Research Council of Canada that I am deeply indebted for financial assitance in Edinburgh and in Montreal, without whose generosity this study could not have been undertaken.

Purified tribulin, an endogenous monoamine oxidase (MAO) inhibitor, has been identified by direct probe insertion mass spectrometry as the indole-2,3-dione, isatin. A gas chromatographic-mass spectrometric assay for isatin has been developed and used to measure its relatively high concentrations in unpurified human urine, and in rat heart and brain. Isatin is a known compound with a broad range of biological activity; this is the first report of its presence in the animal body. Isatin is a potent inhibitor of MAO, particularly of MAO B (IC50, 3 microM), and also binds to central benzodiazepine receptors (IC50 against clonazepam, 123 microM).

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