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Textbook of immunopharmacology
46
Drug design for medicinal chemists X-Ray Crystallography and Drug Action edited by A. S. Horn and C. J. De Ranter, Oxford University Press, 1984. £30.00 (xii + 514 pages) ISBN 0 19 855185 1 This book contains 27 contributions presented at the 9th course of the International School of Crystallography, Erice, Sicily, March 1983. Because of the broad coverage of topics, the title of the book does not optimally correlate with its contents. Indeed, the principal focus is on drug design, particularly on structure-activity relationships (SAR), with X-ray crystallography being the main, but not the sole, structural method considered. As regards drug action and the biological side of the SAR coin, the emphasis is on receptors and on the topography of binding sites. The rationale for the sequence of contributions is not obvious, and the lack of major divisions in the book does not help one to unravel its internal organization. Without too much imagination, however, 4 groups of chapters can be distinguished. A first group of 5 chapters deals mainly with crystals, X-ray crystallography, and the value of the latter in studying molecular conformation and ligand-binding site complexes. Particularly noteworthy are the contribution by Bernstein on crystal forces and molecular conformations, and that of Kollman on drug-receptor binding forces. In the latter chapter, however, the much reduced and black-andwhite presentation of what must have been highly illustrative colour plates is a detrimental shortcut presumably imposed by the publisher. A second group of 8 contributions covers a number of specific receptors and recognition sites on enzymes and other macromolecules. For example, the structural aspects of drug-nucleic acid interactions receive a clear and indepth treatment by Neidle. For the biochemists, there is a valu-
TIPS - January 1985
able presentation by Hol and Wierenga on the 0c-helix dipole and the binding by proteins of phosphate groups. A short but fascinating review by Wilson et al. describes the influenza virus, haemagglutinin. The well-known target dihydrofolate reductase is discussed in two contributions, one richer than the other, which duplicate each other considerably however. Clearly, the editorial pen had run out of red ink, but then camera-ready conference papers seldom, if ever, undergo editorial surgery. The third group of contributions deals with a number of therapeutic classes. Thus, one of the editors aptly summarizes stereochemical aspects of some neuropharmacological agents. Particularly interesting is a systematic and lucid presentation by Merz on the SAR of some synthetic opioids. Neuromuscular blockers, antitumor anthracyclines, and steroids, among others, are also the object of stimulating reviews. In contrast, which credit can be granted to regression equations correlating the activity of 15 benzodiazepines with combinations of independent variables originating from a starting set of
Bridging pharmacology and immunology Textbook of Immunopharmacology edited by M. M. Dale and J. C. Foreman, Blackwell Scientific Publications, 1984. £18.50 (xv ÷ 407 pages) ISBN 0 632 00859 8 I am sure that regular readers of TIPS will have become well aware of the 'new' interdisciplinary field of Immunopharmacology as during the last few years an ever-expanding list of books and journals have appeared devoted to this fastgrowing subject. In the past, general pharmacology texts used in universities have devoted little space to this topic with some small mention of inflammatory and allergic aspects of the field. Thus,
sixty descriptors? In the last part of the book, 5 chapters discuss some novel techniques in drug design, essentially recent computational approaches such as computer graphics. The non-expert will find ample matter of study in the illustrative e x a m ples discussed. The presentation of the book is open to criticism. Several contributors visibly failed to read the instructions for the preparation of their camera-ready chapter. As a result, an amusing fantasy prevails in the format of references, and the legibility of a few typings not optimal. Many figures are too small, and colour photographs would have been helpful in several cases. From a global scientific viewpoint, this book is a wide but not really coherent collection of contributions, several quite good, some rather superficial and lacking originality. But despite these defects, the book allows a fruitful and broad comparison of approaches and viewpoints, and provides much information. As such, it will be found useful and stimulating by drug researchers in general, and medicinal chemists in particular. BERNARD TESTA
The author is Professor and Head of Medicinal Chemistry at the University of Lausanne, Switzerland.
the interested student or academic has been forced to search for the original literature or to use one or other of the specialized text books which assume a considerable basic knowledge of both immunology and pharmacology. Now a book has appeared which attempts to bridge this gap and which, in the main, appears to answer the problem. Drs Dale and Foreman have compiled a series of articles based on the pharmacology final year undergraduate course in immunopharmacology run at University College, London. There certainly seems to be considerable enthusiasm for the subject amongst students and this book provides an excellent grounding for both the interested undergraduate and the clinician or academic with little background in the field. The editors have gathered a dis-
47
TIPS - January 1985 t i n g u i s h e d group of practising scientists to write the chapters which are generally clearly and concisely presented. The b o o k is d i v i d e d into four sections dealing with the cells a n d then the m e d i a tors involved, the p a t h o p h y s i o logy of inflammation and finally drug m a n i p u l a t i o n of the i m m u n e response. Each chapter has a brief guide to further r e a d i n g and there is a reasonably c o m p r e h e n s i v e index. This b o o k concentrates its attention to a large degree u p o n aspects of the inflammatory response and this e m p h a s i s will be less satisfactory to the reader looking for immunological details. In this context there is, for example, little m e n t i o n of m o d u l a t i o n of l y m p h o cyte function and the extensive literature on the interactions between these cells. There is also no m e n t i o n of p r o b l e m s of i m m u n o toxicity, drug-related i m m u n e reactions, environmental factors in the i m m u n e response or the use of monoclonal a n t i b o d i e s as p h a r m a cological tools, all legitimate areas for discussion in a c o m p r e h e n s i v e
Linking the threads of pain Advances in Inflammation Research Vol. 6, Side Effects of A n t i - i n f l a m m a t o r y and Analgesic Drugs edited by K. D. Rainsford and G. Velo, Raven Press Books, 1984. $48.50 (xiv + 306 pages) ISBN 0 890 04971 8 As its title indicates this b o o k concentrates on the side effects a n d general toxicology of the non-steroidal a n t i - i n f l a m m a t o r y and analgesic drugs currently available for the treatment of the arthritic diseases, and for analgesia. The b o o k is essentially an e d i t e d collation of 30 or so research p a p e r s and reviews w h i c h were p r e s e n t e d at an international m e e t i n g in Verona in S e p t e m b e r 1982, and w h i c h have been categorized u n d e r different headings. The a u t h o r s h i p is w i d e and includes epidemiologists, r h e u m a tologists, pathologists, clinicians and pharmacologists from universities and pharmaceutical comp a n i e s in different parts of the world. The book is s u b d i v i d e d into a
i
general immunopharmacology text. Thus, although two chapters b y Marshall Plaut on basic lymphocyte function and John Morley's group on l y m p h o k i n e s are certainly useful contributions, the b o o k is very much balanced in favour of the 'inflammologists'. The reader also should not expect to find detailed m e t h o d o l o g y in this book. This comparative lack of fundamental i m m u n o l o g y p u t s the reader at some d i s a d v a n t a g e w h e n one comes to consider the chapters in the final section dealing w i t h immunomodulators.
series of sections b e g i n n i n g w i t h 3 p a p e r s u n d e r the h e a d i n g of epidemiology, drug distribution and p o s t - m a r k e t i n g surveillance. This is followed b y two sections on the adverse effects w h i c h can occur on the gastrointestinal tract, the first section dealing w i t h clinical studies and the second section concentrating on studies in laboratory animals. The next four sections follow the same pattern. They describe clinical and laboratory studies on renal a n d hepatic side effects, w i t h the last two sections concerned w i t h asthma and h y p e r s e n s i t i v i t y reactions, a n d the toxic effects particular to certain drugs. The whole volume makes stimulating r e a d i n g because each p a p e r views a small group of associated p r o b l e m s from a series of different angles. To take some examples at r a n d o m : the p a p e r b y L. F. Prescott discusses in a brief b u t w i d e - r a n g i n g w a y the analgesic n e p h r o p t h y in man associated w i t h aspirin, p h e n a c e t i n a n d paracetamol. This links nicely w i t h a n o t h e r p a p e r on the renal toxicity of a s p i r i n in SLE and other arthropathies b y K. P. Kimberley, and w i t h other papers
Despite m y relatively m i n o r reservations I can strongly recomm e n d this v o l u m e to b o t h interested students, and teachers looking for a text u p o n w h i c h to base a course in this e x p a n d i n g area of pharmacology, as the b o o k p r o v i d e s a very readable basic introduction to the m e c h a n i s m s involved in b o t h i m m u n e and n o n - i m m u n e aspects of host defense. MICHAEL BRAY
The author is Laborleiter at Ciba-Geigy Ltd, Basel, Switzerland.
w h i c h discuss renal p r o s t a g l a n d i n p r o d u c t i o n in m a n and the effects of aspirin on the k i d n e y s of rats and pigs. So there is a w o v e n w e b of interconnecting threads between these p a p e r s w h i c h ties the e p i d e m i o l o g y , toxicology and p h a r m a c o l o g y of these drugs into a most effective fabric. Perhaps the most constructive aspect of this volume is that it p r o v i d e s a very b r o a d forum of authoritative discussion from w h i c h a fuller u n d e r s t a n d i n g can be d e v e l o p e d of h o w and w h y these drugs have their toxic effects, out of w h i c h it m a y also (hopefully) be possible to p u r s u e research w h i c h leads to the devel o p m e n t of drugs w h i c h are less toxic. Unlike some s y m p o s i a w h i c h give the i m p r e s s i o n of b e i n g little more than a thin excuse for an international jamboree, this one certainly had a constructive outcome, and those w h o are concerned with the devel o p m e n t of NSAID should certainly find this volume of value and interest. IVAN STOCKLEY
The author is Lecturer in Pharmacology, Department of Physiology and Pharmacology, University of Nottingham, Nottingham, UK.
Drug design for medicinal chemists X-Ray Crystallography and Drug Action edited by A. S. Horn and C. J. De Ranter, Oxford University Press, 1984. £30.00 (xii + 514 pages) ISBN 0 19 855185 1 This book contains 27 contributions presented at the 9th course of the International School of Crystallography, Erice, Sicily, March 1983. Because of the broad coverage of topics, the title of the book does not optimally correlate with its contents. Indeed, the principal focus is on drug design, particularly on structure-activity relationships (SAR), with X-ray crystallography being the main, but not the sole, structural method considered. As regards drug action and the biological side of the SAR coin, the emphasis is on receptors and on the topography of binding sites. The rationale for the sequence of contributions is not obvious, and the lack of major divisions in the book does not help one to unravel its internal organization. Without too much imagination, however, 4 groups of chapters can be distinguished. A first group of 5 chapters deals mainly with crystals, X-ray crystallography, and the value of the latter in studying molecular conformation and ligand-binding site complexes. Particularly noteworthy are the contribution by Bernstein on crystal forces and molecular conformations, and that of Kollman on drug-receptor binding forces. In the latter chapter, however, the much reduced and black-andwhite presentation of what must have been highly illustrative colour plates is a detrimental shortcut presumably imposed by the publisher. A second group of 8 contributions covers a number of specific receptors and recognition sites on enzymes and other macromolecules. For example, the structural aspects of drug-nucleic acid interactions receive a clear and indepth treatment by Neidle. For the biochemists, there is a valu-
TIPS - January 1985
able presentation by Hol and Wierenga on the 0c-helix dipole and the binding by proteins of phosphate groups. A short but fascinating review by Wilson et al. describes the influenza virus, haemagglutinin. The well-known target dihydrofolate reductase is discussed in two contributions, one richer than the other, which duplicate each other considerably however. Clearly, the editorial pen had run out of red ink, but then camera-ready conference papers seldom, if ever, undergo editorial surgery. The third group of contributions deals with a number of therapeutic classes. Thus, one of the editors aptly summarizes stereochemical aspects of some neuropharmacological agents. Particularly interesting is a systematic and lucid presentation by Merz on the SAR of some synthetic opioids. Neuromuscular blockers, antitumor anthracyclines, and steroids, among others, are also the object of stimulating reviews. In contrast, which credit can be granted to regression equations correlating the activity of 15 benzodiazepines with combinations of independent variables originating from a starting set of
Bridging pharmacology and immunology Textbook of Immunopharmacology edited by M. M. Dale and J. C. Foreman, Blackwell Scientific Publications, 1984. £18.50 (xv ÷ 407 pages) ISBN 0 632 00859 8 I am sure that regular readers of TIPS will have become well aware of the 'new' interdisciplinary field of Immunopharmacology as during the last few years an ever-expanding list of books and journals have appeared devoted to this fastgrowing subject. In the past, general pharmacology texts used in universities have devoted little space to this topic with some small mention of inflammatory and allergic aspects of the field. Thus,
sixty descriptors? In the last part of the book, 5 chapters discuss some novel techniques in drug design, essentially recent computational approaches such as computer graphics. The non-expert will find ample matter of study in the illustrative e x a m ples discussed. The presentation of the book is open to criticism. Several contributors visibly failed to read the instructions for the preparation of their camera-ready chapter. As a result, an amusing fantasy prevails in the format of references, and the legibility of a few typings not optimal. Many figures are too small, and colour photographs would have been helpful in several cases. From a global scientific viewpoint, this book is a wide but not really coherent collection of contributions, several quite good, some rather superficial and lacking originality. But despite these defects, the book allows a fruitful and broad comparison of approaches and viewpoints, and provides much information. As such, it will be found useful and stimulating by drug researchers in general, and medicinal chemists in particular. BERNARD TESTA
The author is Professor and Head of Medicinal Chemistry at the University of Lausanne, Switzerland.
the interested student or academic has been forced to search for the original literature or to use one or other of the specialized text books which assume a considerable basic knowledge of both immunology and pharmacology. Now a book has appeared which attempts to bridge this gap and which, in the main, appears to answer the problem. Drs Dale and Foreman have compiled a series of articles based on the pharmacology final year undergraduate course in immunopharmacology run at University College, London. There certainly seems to be considerable enthusiasm for the subject amongst students and this book provides an excellent grounding for both the interested undergraduate and the clinician or academic with little background in the field. The editors have gathered a dis-
47
TIPS - January 1985 t i n g u i s h e d group of practising scientists to write the chapters which are generally clearly and concisely presented. The b o o k is d i v i d e d into four sections dealing with the cells a n d then the m e d i a tors involved, the p a t h o p h y s i o logy of inflammation and finally drug m a n i p u l a t i o n of the i m m u n e response. Each chapter has a brief guide to further r e a d i n g and there is a reasonably c o m p r e h e n s i v e index. This b o o k concentrates its attention to a large degree u p o n aspects of the inflammatory response and this e m p h a s i s will be less satisfactory to the reader looking for immunological details. In this context there is, for example, little m e n t i o n of m o d u l a t i o n of l y m p h o cyte function and the extensive literature on the interactions between these cells. There is also no m e n t i o n of p r o b l e m s of i m m u n o toxicity, drug-related i m m u n e reactions, environmental factors in the i m m u n e response or the use of monoclonal a n t i b o d i e s as p h a r m a cological tools, all legitimate areas for discussion in a c o m p r e h e n s i v e
Linking the threads of pain Advances in Inflammation Research Vol. 6, Side Effects of A n t i - i n f l a m m a t o r y and Analgesic Drugs edited by K. D. Rainsford and G. Velo, Raven Press Books, 1984. $48.50 (xiv + 306 pages) ISBN 0 890 04971 8 As its title indicates this b o o k concentrates on the side effects a n d general toxicology of the non-steroidal a n t i - i n f l a m m a t o r y and analgesic drugs currently available for the treatment of the arthritic diseases, and for analgesia. The b o o k is essentially an e d i t e d collation of 30 or so research p a p e r s and reviews w h i c h were p r e s e n t e d at an international m e e t i n g in Verona in S e p t e m b e r 1982, and w h i c h have been categorized u n d e r different headings. The a u t h o r s h i p is w i d e and includes epidemiologists, r h e u m a tologists, pathologists, clinicians and pharmacologists from universities and pharmaceutical comp a n i e s in different parts of the world. The book is s u b d i v i d e d into a
i
general immunopharmacology text. Thus, although two chapters b y Marshall Plaut on basic lymphocyte function and John Morley's group on l y m p h o k i n e s are certainly useful contributions, the b o o k is very much balanced in favour of the 'inflammologists'. The reader also should not expect to find detailed m e t h o d o l o g y in this book. This comparative lack of fundamental i m m u n o l o g y p u t s the reader at some d i s a d v a n t a g e w h e n one comes to consider the chapters in the final section dealing w i t h immunomodulators.
series of sections b e g i n n i n g w i t h 3 p a p e r s u n d e r the h e a d i n g of epidemiology, drug distribution and p o s t - m a r k e t i n g surveillance. This is followed b y two sections on the adverse effects w h i c h can occur on the gastrointestinal tract, the first section dealing w i t h clinical studies and the second section concentrating on studies in laboratory animals. The next four sections follow the same pattern. They describe clinical and laboratory studies on renal a n d hepatic side effects, w i t h the last two sections concerned w i t h asthma and h y p e r s e n s i t i v i t y reactions, a n d the toxic effects particular to certain drugs. The whole volume makes stimulating r e a d i n g because each p a p e r views a small group of associated p r o b l e m s from a series of different angles. To take some examples at r a n d o m : the p a p e r b y L. F. Prescott discusses in a brief b u t w i d e - r a n g i n g w a y the analgesic n e p h r o p t h y in man associated w i t h aspirin, p h e n a c e t i n a n d paracetamol. This links nicely w i t h a n o t h e r p a p e r on the renal toxicity of a s p i r i n in SLE and other arthropathies b y K. P. Kimberley, and w i t h other papers
Despite m y relatively m i n o r reservations I can strongly recomm e n d this v o l u m e to b o t h interested students, and teachers looking for a text u p o n w h i c h to base a course in this e x p a n d i n g area of pharmacology, as the b o o k p r o v i d e s a very readable basic introduction to the m e c h a n i s m s involved in b o t h i m m u n e and n o n - i m m u n e aspects of host defense. MICHAEL BRAY
The author is Laborleiter at Ciba-Geigy Ltd, Basel, Switzerland.
w h i c h discuss renal p r o s t a g l a n d i n p r o d u c t i o n in m a n and the effects of aspirin on the k i d n e y s of rats and pigs. So there is a w o v e n w e b of interconnecting threads between these p a p e r s w h i c h ties the e p i d e m i o l o g y , toxicology and p h a r m a c o l o g y of these drugs into a most effective fabric. Perhaps the most constructive aspect of this volume is that it p r o v i d e s a very b r o a d forum of authoritative discussion from w h i c h a fuller u n d e r s t a n d i n g can be d e v e l o p e d of h o w and w h y these drugs have their toxic effects, out of w h i c h it m a y also (hopefully) be possible to p u r s u e research w h i c h leads to the devel o p m e n t of drugs w h i c h are less toxic. Unlike some s y m p o s i a w h i c h give the i m p r e s s i o n of b e i n g little more than a thin excuse for an international jamboree, this one certainly had a constructive outcome, and those w h o are concerned with the devel o p m e n t of NSAID should certainly find this volume of value and interest. IVAN STOCKLEY
The author is Lecturer in Pharmacology, Department of Physiology and Pharmacology, University of Nottingham, Nottingham, UK.