"He who is faithfully analysing ... epi lepsy is doing far more than studying epilepsy" Hughlings Jackson Modifying this well-known statement by Jackson, one could say today: "He who is faithfully analysing anti-epileptic drugs is doing far more than studying anti-epileptic drugs." For these drugs not only serve to prevent epileptic fits and thus advance the treatment of epilepsy, they are also effective in the treatment of cardiac arrhythmias and trigeminal neuralgia. Furthermore, clinical pharmacologists consider anti-epi leptic drugs as model drugs in pharmacokinetics and pharmocodynamics, since reliable methods are available for their determination and their effects and side effects can be defined. The methods of estimating of drugs in body fluids provide a tool that enables us to throw light on many obscure relationships in pharmaceutical treatment. Now that we can study the pharmacokinetics and interaction of drugs in man, many hypotheses based on clinical experience alone may well be eliminated or corroborated. The grow ing body of knowledge will make us more careful about the administration of drugs in combination. Now that we can study how biological parameters interfere with drug action, we may perhaps proceed to the scientific analysis of many clinical observations that suggest the importance of such factors as age, sex, menstrual cycle, pregnancy, fever, diet, stress, sport, climate, and altitude."

This volume is the completion of work initially planned several years ago as a compilation of selected aspects of the biological effects of fluorides. The first portion appeared in Volume XXII (1966) of this Handbuch, under the title "Pharmacology of Fluorides, Part 1. " Inasmuch as the present volume is an integral part of the original project, justification for offering it to the scientific community remains the same as that originally set forth. This may be recapitulated as follows. The tremendous increase in the annual production of fluorides over the amounts produced thirty years ago, together with the increased diversity of their uses has correspondingly increased the hazard associated with these materials. That is to say, the possibilities of encountering their characteristic toxic effects under the conditions of their use has increased because the variety, amounts and ways of usage have increased. Their inherent toxicity, of course has not changed, but the increased hazard has led to a vast increase in the amount and scope of research reported. It is the purpose of these volumes to review selected aspects of this literature. Rochester, N. Y. , February 1970 FRANK A. SMITH Acknowledgements Even the casual reader of this volume will soon realize that contributing authors, as well as those contributing to its predecessor, Volume XX/I, have made good use of tables of data, figures and pertinent quotations from previously published work.

The book provides a comprehensive account of ticks and tick-borne diseases occurring in tropical and subtropical areas. It begins with a complete up-to-date overview of the systematics of the Ixodida (Ixodidae, Argasidae and Nutalliellidae) and is followed by a review of the problem of ticks and tick-borne diseases of domestic animals world wide. This leads on to multi-disciplinary approaches to planning tick and tick-borne disease control and to contributions on calculating the economic impact of a tick species such as Amblyomma americanum on beef production systems. Heartwater fever (cowdriosis) and dermatophilosis are endemic in Africa and pose a threat to the North American mainland. The epidemiology of these two diseases is discussed in detail as is the role of frozen vaccines to control bovine babesiosis and anaplasmosis. The book also includes chapters on tick transmitted zoonoses such as Lyme borreliosis, tick typhus and ehrlichiosis. It concludes with a review of the acaricidal treatment of tick infestation.

The volumes of this classic series, now referred to simply as "Zechmeister" after its founder, L. Zechmeister, have appeared under the Springer imprint ever since the series' inauguration in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline.

" ... this is an excellent compilation of data which should be on the bookshelves of all analysts interested in the benzodiazepines. It is to be hoped that, with the introduction of so many new ben zodiazepines, the author will quickly add these in a second edi tion" (A. C. Moffat in: Trends in Analytical Chemistry, 1983). This review, deputizing for many others, reflects the friendly reception enjoyed by the first volume of Benzodiazepines, which was published in 1982 and apparently closed a gap in the ben zodiazepine literature. In the meantime, Benzodiazepines has established itself as a standard book, as evidenced by numerous letters and quotations. Suggestions were also soon made for a new edition in view of the unusually rapid development in the field of the benzodiazepines. It became quickly obvious, however, that it would not be sufficient to publish a revised second edition, but that a completely new second volume would be required for which, however, the successful previous format could be largely retained. The following considerations seem worth mentioning in connection with the preparation of Volume II: - To ensure continuity with Volume I as far as possible, the list of references was consecutively numbered (references 1 to 3779 in Volume I, references 3780 to 11338 in Volume II). Whereas in Vol. I the substances appear in the sequential order of their historical development they are listed in alphabetical order in Vol. II."

Bradykinin is frequently referred to as an elusive substance; the editor of a comprehensive volume dealing with kinins thus has a difficult task. The com plexity of the issues calls for a large number of contributors who approach the topics from the various angles that are dictated by the sometimes divergent views of the individuals. The editor saw no reason to prescribe the mode of presentation, which was left to the authors and accounts for the variety of approaches. Contributors from nine countries were asked to participate in the volume. The chapters were organized to present, first, the history of the discoveries and methods of approach to kinin research. Then follows a discussion of the enzymes that release kinins, their substrates, and other enzymes that inactivate the peptides. If the release of kinin is important, then the inhibition of the releasing enzymes is of obvious interest and is described. Since the measurement of kinin ogen levels in blood has been frequently used as an indicator of kinin liberation, in addition to a separate chapter, kininogens are also mentioned where the functions of kinins are discussed. The conclusions drawn from establishing structure-action relationships for many analogs and the actions of kinins are indicated and summarized."

One of the currently most expanding and exciting areas in cardiovascular research is the study of receipt and dispatch of chemical signals by different cell types. Major progress has been made during the last years and a number of intercellular mediators have been structurally identified and their regulation studied. The impressive developments in molecular biology have provided most effective tools, enabling us to understand message generation in much more detail than anyone would have appreciated a couple of years ago. These developments also have a major impact on cardiovascular pharmacology. This involves both the molecular design of new drugs as well as an improved understanding of how established drugs act. Clearly, changes in one mediator system will also affect others and it might be difficult to take out just one factor and to ignore others. This is definitely true for myocardial ischemia where many different mediators are synthesized and released at about the same time, resulting in a complex picture of events and an even more difficult selection of the most appropriate drug therapy.

Twelve years have elapsed since the appearance of the first volume and it is with great pleasure that the Editor is now able to present volume 15. During these twelve years various fields of drug research have undergone important, partly revolutionary, changes. A number of these have already been dealt with, so that the series PROGRESS IN DRUG RESEARCH contains a comprehensive review of a substantial part of our current knowledge. The Editor is particularly grateful for the opportunity of transmitting to those connected with the development of drugs the extensive knowledge of the Authors, who, without exception, are themselves actively engaged in research. Drug research is currently in a state of transformation: reconsideration in the light of the past and reorientation with a view to the future. To a large extent this is due to the tumultuous developments in the last 20 years, developments which are unparalleled in the history of medicine and the consequences of which cannot yet be completely evaluated. Unfortunately, however, the current situation is not devoid of its unpleasant and even tragic aspects, aspects which fall outside the research worker's sphere or influence. Those connected with drug research, be they in industry, in universities or in clinics, are aware of these problems, and, as a result of this awareness, are all the more in need of an aid which will assist them in ascertaining the current position and in fixing future goals.

The importance of ambident reactivity in synthetic and mecha nistic organic chemistry cannot be overemphasized. It is therefore all the more frustrating that the breadth and diffuseness of the subject make the retrieval of information from the primary literature a difficult and onerous task, especially for the researcher who wishes to gain an overview of the factors influencing ambident behavior or an in-depth knowledge of the reactivity of a specific ambident system. The present volume is an attempt to meet these needs, at least as far as ambident anions are concerned. As a reference work combining under one cover an account of the factors underlying ambident behavior, a survey of the chemistry of the most important ambident anions (with especial emphasis on enolates), and a comprehensive compilation of recent key references, important but less well known citations from the nineteenth and early twentieth century literature, and relatively inaccessible data from the Soviet literature, this translation goes some way to filling a conspicuous gap in the mono graph literature of an important facet of organic chemical reactivity."

Volume 45 of "Progress in Drug Research" contains eight reviews and the various indexes which facilitate its use and establish the connection with the previous volumes. The articles in this volume deal with neuro peptides as native immune modulators, with Calmodulin and with effects of cell stimuli and drugs on cellular activation, with recent advances in benzodiazepine receptor binding studies, with the medicinal chemistry and therapeutic potentials of ligands of the histamine H3 receptor, with Serotonin uptake inhibitors, with computer-aided drug design, with natri uretic hormones and with the recent developments in the chemotherapy of osteoporosis. In the 36 years that PDR has existed, the Editor has enjoyed the valu able help and advice of many colleagues. Readers, the authors of the reviews and, last but not least, the reviewers have all contributed greatly to the success of this series. Although the comments received so far have generally been favorable, it is nevertheless necessary to analyze and to reassess the current position and the future direction of such a series of monographs. So far, it has been the Editor's intention to help disseminate information on the vast domain of drug research, and to provide the reader with a tool with which to keep abreast of the latest developments and trends. The reviews in PDR are useful to the nonspecialist, who can obtain an overview of a particular field of drug research in a relatively short time."

This volume comprises the edited proceedings of the International Taurine Sympo sium held in Osaka, Japan, in June 1995, as a Satellite Symposium of the 15th Biennial of the International Society for Neurochemistry. This Taurine Symposium was the Meeting latest in a series held since 1975 at approximately two-year intervals by an informal group of international researchers. It attracted contributions from 20 countries, ranging from Armenia via Finland and Spain to the United States. Some 121 participants attended. The Symposium was organized and chaired by Junichi Azuma, University of Osaka. Other members of the Organizing Committee in Japan consisted of Kinya Kuriyama and Masao Nakagawa, both from the Kyoto Prefectural University of Medicine, and Akemichi Baba, from Osaka University. The Committee had to contend with the disaster of the Kobe earthquake, which struck on January 21. The epicenter was only around 25 miles from the meeting site, and the quake demolished the home of one Committee member. Despite this unnaturally natural handicap, the participants experienced a superbly organized meeting, one which more than maintained the high social and scientific standards established for this series. In his Welcome Message, Dr. Azuma listed a threefold objective for the Symposium: To provide a forum for the interdisciplinary exchange of information on taurine; to give an opportunity for renewing old friendships and making new friends; and to promote coopera tion among participants from around the world."

Volume 40 of "Progress in Drug Research" contains six reviews and the various indexes which facilitate its use and establish the connec tion with the previous volumes. The articles in this volume deal with phosphodiesterase inhibitors and their therapeutic potential in asthma; peptide receptor ligand drugs; aldose reductase inhibitors; the design and discovery of new drugs by stepping-down and stepping-up approaches; new synthetic ligands for L-type voltage gated calcium channels and with luteolytic agents in fertility regula tion. III the 33 years that "Progress in Drug Research" has existed, the Edi tor has enjoyed the valuable help and advice of many colleagues. Readers, the authors of the reviews, and last but not least, the review ers have all contributed greatly to the success of this series. Although the comments received so far have generally been favorable, it is nevertheless necessary to analyze and to reassess the current position and the future direction of such a review series."

This volume of the Handbook of Experimental Pharmacology (Concepts in Biochemical Pharmacology) will show that pharma cology has finally arrived as a true discipline in its own right, and is no longer the handmaiden of organic chemistry and physiology. Instead it is an amalgam of all the biological sciences including biochemistry, biophysical chemistry, physiology, pathology and clinical medicine. In the volumes that make up Concepts in Bio chemical Pharmacology we hope to convince Medical Schools what should now be obvious, that pharmacology is no longer that dull topic bridging the basic sciences with medicine, but is probably the most important subject in the medical curriculum. We are grateful for the advice of Dr. Byron Clark, Director of the Pharmacology-Toxicology Program at the National Institutes of Health whose support made possible much of the work described in this volume. Contents Section Four: Methods 01 Stooging the MetoholiBm 01 Drugs Subsection A. Assay 01 Drugs and Their M etoholites Chapter 22: Basic Principles in Development of Methods for Drug Assay. B. B. BRODIE. With 2 Figures 1 1 A. Introduction . . . . . . . . . . B. Principles of Developing a Method. . . . . . 1 I. Section of Method of Assay . . . . . . 1 II. Choice of Solvent for Extraction of Drug 2 III. Adsorption of Drugs by Glass Surfaces . . . . . . . . . . . . . . 3 IV. Recoveries of Known Amounts of Compound from Biological Material. 4 V. Assessment of Sensitivity 5 VI. Assessment of Specificity 5 References. . . . . . . . . . ."

Wenn uber Fortschritte der Chemie der Gallotannine berichtet werden soll, so muss ein Ausgangspunkt gewahlt werden, von dem aus die neu gewonnenen Erkenntnisse geschildert werden. Das ist in unserem Falle nicht schwer. EMIL FISCHER hatte fur das chinesische Gallotannin (aus den Blattgallen von Rhus semialata) und das turkische Gallotannin (aus den Zweiggallen von Quercus infectoria) das bekannte Bauprinzip der polygalloylierten Glucosen herausgearbeitet. Aber weder ihm noch KARRER (43, 44) ist es moglich gewesen, aus dem Gemisch von Substanzen, die sie untersuchten, einzelne Individuen zu isolieren, deren exakte Konstitution man hatte aufklaren und angeben konnen. Auch mit den modernen Methoden der Gegenstromverteilung und Verteilungschromato graphie ist eine Auf trennung dieser Gemische offenbar bis heute noch nicht gelungen. Ahnlich liegen die Verhaltnisse beim Sumach-Gerbstoff (aus Rhus coriaria), von dem MUNz (58) gezeigt hat, dass der Hauptteil der Substanz aus einer Pentagalloyl-glucose besteht. Erwahnt man noch das Glucogallin und Tetrarin, die GILSON (30, 30a) aus chinesischem Rhabarber isoliert hat, und das Acertannin, ein Digalloyl-anhydrohexit aus koreanischem Acer ginnale, von PERKIN und UYEDA (65), so hat man die im Jahre 1929 bekannten Forschungsergebnisse zusammengestellt, mit Ausnahme des Hamameli-tannins und der Chebulinsaure, die aber im nachstehenden Bericht noch ausfuhrlicher behandelt werden. Somit kann also das Jahr 1929 als Ausgangspunkt fur die vorliegende Berichterstattung gewahlt werden. 11. Gallotannine: Ellagsaure-freie Gerbstoffe. I. Hamameli-tannin."

Volume 24 includes six contributions, the author and paper index of volumes 1-24 and the key-word index. Since volume 23 included an index for volumes 16-23 the reader has the possibility to use these monographs as an encyclopedia and is in the position to find references to almost all fields of drug research. The editor hopes that the articles of the present volume will prove interesting and useful to many scientists and would be grateful to receive suggestions and opinions from readers, as in the past case over the 20 years in which this series of monographs has existed. In this respect, thanks are due to all colleagues who have provided helpful criticism of past volumes, thereby helping the editor in his work. Dr. A. Naf again has assisted the editor and has carefully reviewed all manuscripts, formulae and references, and has corrected the proofs. Thanks are due to him for this immense work. At the same time, the editor would like to thank the publishers and printers, Verlag Birkhliu ser, in particular Messrs. Th. Birkhliuser and C. Einsele, for the excellent cooperation and the work they have accomplished."

Volume 21 of "Progress in Drug Research" contains 5 contributions from various areas of drug research and therapy. As in previous volumes, in the present volume the authors have also tried not only to summarise the current status of particular fields of drug research, but also to provide leads for future research activity. The various contributions in this volume will be of especial value not only to those actively concerned in resolving the diverse problems in drug research, but also to those who wish to keep abreast ofthe latest developments in- fluencing modem therapy. In addition, it is believed that volume 21 and the previous 20 volumes of "Progress in Drug Research" so far published represent a useful reference work of an encyclopaedic character. The editor would also like to take this opportunity of expressing his gratitude to Dr. A. Naffor carefully working over the manuscripts and correcting proofs. Thanks are also due to the publishers and the printers, Druckerei Birkhauser, especially to Dr. A. Birkhauser, Th. Birkhiiuser and C. Einsele, for their painstaking work on the printing and lay-out of the volume. August 1977 Dr. E. JUCKER Sandoz AG, Basel Vorwort Der 21. Band der "F ortschritte der Arzneimittelforschung" umfasst 5 Beitriige aus verschiedenen Gebieten der Arzneimittelforschung> und der Therapie.

A comprehensive guide to multiple sclerosis, discussing: clinical features, diagnosis, disease-modifying therapy, & symptom & medical management written by world-renowned experts in neurology, specifically MS. Dr Cohen and Dr Rae-Grant who are renowned researchers and physicians in the field of MS and are investigators on several key drug trials.

Extensive use of illustrations and succinct format makes this book an easily accessible and key reference guide.

Reviews cutting-edge agents currently in development, while also discussing the clinical features and standard diagnosing criteria and practices of MS from the clinician s perspective

Designed to include thorough descriptions of standard and novel treatment therapies in MS.

Explains how to most effectively use the top therapies in MS in the context of a clinical practice and based on investigational trials.

Concise but comprehensive

Over the past 30 years, there have been significant advances in our understanding of MS due to the use of MRIs to better visualize the disease and due to the introduction of new ameliorating drugs. However, MS is still an incurable disease and diagnosis remains challenging for many physicians; for instance, symptoms often mimic MS, and there is no specific test for the disease. To ensure optimal patient care, there is a need for physicians to remain up to date with new drugs on the market, disease detection, diagnosis, and latest management options.

The Handbook of Multiple Sclerosis provides a concise, easily accessible guide for all healthcare professionals involved in the diagnosis and management of this condition, including standard therapies, as well as more novel treatments. The book will also include comprehensive evaluations of the pharmacological treatments available, including novel investigational agents currently in development.

"

All the important pharmacological interactions affecting thyroid function are described in this book. The first section is devoted to the physiology and biochemistry of thyroid disease, putting the pharmacological interactions into perspective. The second section reviews all the important pharmacological effects on thyroid function and also deals with the impact of other environmental agents. The chapters are written by internationally recognised experts and extensively referenced to provide an up-to-date review of the pharmacological interactions important to the thyroid and its diseases.

One of the most active areas of contemporary organic chemistry involves the search for new catalysts that borrow concepts, strategies and even components from enzymes but yet are not found in nature. Such artificial enzymes not only give enormous insights into the mechanisms of enzyme catalysis but also offer the potential for catalyzing a wide range of chemical reactions with no counterpart in nature. Several approaches have been taken in the deVelopment of new catalysts, some based on biological methods and others on synthetic techniques. Site directed mutagenesis has allowed the direct replacement of amino acids in an enzyme with resulting changes in stability, selectivity and mechanism. Recent developments have shown that even non-natural amino acids can be incorporated into proteins and also that enzymes can function effectively in organic solvents. A different biological route to artificial enzymes has exploited the immune system and its ability to generate millions of antibodies to a given antigen. Novel antigens have been designed to mimic the transition states of chemical reactions. Antibodies elicited against these antigens thus contain an active site that is complementary to transition state structure and can potentially catalyze target reactions. A broad range of reactions can now be 6 catalyzed using the method with rate accelerations reaching 10 compared to the control reactions. Protein engineering and catalytic antibodies represent complex solutions to the problem of artificial enzymes. Their complexity is however their principal limitation.

Volume 41 of "Progress in Orug Research" contains eight reviews and the various indexes which facilitate its use and establish the con nection with the previous volumes. The articles in this volume deal with teratogenesis; nephrotoxicity; bacterial resistance to P. lactam antibiotics; eradication of diseases by vaccination; chirality and drug design; endogenous digitalis-like factors; erythropoietin; and sero tonin (5HT)-antagonists. 3 All these articles give an excellent overview of the respective fields of research. In the 33 years that POR has existed, the Editor has enjoyed the valu able help and advice of many colleagues. Readers, the authors of the reviews, and last but not least, the reviewers have all contributed greatly to the success of this series. Although the comments received so far have generally been favorable, it is nevertheless necessary to analyze and to reassess the current position and the future direction of such a review series. So far, it has been the Editors intention to help disseminate informa tion on the vast domain of drug research, and to provide the reader with a tool with which to keep abreast of the latest developments and trends. The reviews in POR are useful to the non-specialists, who can obtain an overview of a particular field of research in a relatively short time. The specialist readers of POR will appreciate the reviews' comprehensive bibliographies, and, in addition, they may even get fresh impulses for their own research."

Contrast media are drugs by default. Had there been no default, there would be no need for a related pharmacology, and thus no need for this book. Radiographic contrast media (CM) are substances whose primary purpose is to enhance diagnostic information of medical imaging systems. The position of CM in pharmacology is unique. First, there is the unusual requirement of biological inertness. An ideal CM should be completely biologically inert, i.e., stable, not pharmacologically active, and efficiently and innocuously excretable. Because they fail to meet these requirements, CM must be considered drugs. The second unusual aspect of CM is that they are used in large quantities, their annual production being measured in tens of tons. It is not in spite of, but because of, the increased use of new radiographic systems, computed tomography, digital radiography, etc., that consumption is on the rise. And, it is not likely that the other emerging imaging modalities - NMR, ultrasonography, etc. - will displace radiographic CM soon; it is quite probable that these remarkable compounds will continue to play an active role in diagnostic imaging in the foreseeable future.

The 19th volume deals, as did its predecessor, with current problems of tropical medicine. Both volumes are based on various international Symposia which were held in Bombay on the occasion of the 75-year Platinum Jubilee of the Haffkine Institute in the Spring of 1974. The contributions in the 19th volume are based on lectures at thetast three Symposia which dealt with Helminthiasis, Diphtheria, Pertussis, Tetanus and Cholera. The 70 articles provide the reader with an impressive cross-section of the current state of specialized knowledge on the subject and the outstanding problems. Even today, researchers from various disciplines are still confronted with numerous unsolved problems in tropical medicine, and it is to be hoped that the 18th and 19th volumes will provide a stimulus for intensified research in the area of tropical medicine. The editor further hopes that, in the future, a still more fruitful co-operation between developed and developing countries will come about. The editor owes special thanks to Dr. Rafiq Zakaria, Minister, Dr. Gaitonde, as well as Dr. Anand and Dr. Chadha, who were responsible for the organisa tion of the Symposia on which the 19th volume is based. Thanks are also extended to Dr. A. Niif for his conscientious revision of the manuscripts and correction of the galley proofs. In addition, thanks are due to the publishers and the printers, Birkhiiuser, especially to Dr. A. Birkhiiuser, Th. Birkhauser and C. Einsele for their accurate printing and fine presentation of the volume."