Advances in molecular biology describing important enzyme systems involved in drug conjugation and deconjugation reactions and recent work indicating the importance of drug and xenobiotic conjugates as transport forms of biologically active compounds are reviewed comprehensively. Part One describes molecular events associated with the expression and regulation of transferases and hydrolases involved in Phase II drug conjugation and deconjugation. Part Two deals with the regulation of Phase II conjugation, and Part Three reviews critically the importance of drug conjugates in pharmacology and...

It has been almost 20 years since the discovery by Kohler and Milstein of the technology to produce monoclonal antibodies (MAbs), a discovery that promised revolutionary changes in research, clinical diagnosis and human therapy. From today's perspective, it is fair to conclude that this promise has been realized in two areas of the three. As research tools, MAbs have been invaluable: their ability to selectively bind and localize specific antigens, detect and identify new ligands and their receptors, and agonize and/or antagonize specific molecular interactions continues to provide a useful...

In recent years alcohol abuse has received increased international attention. Such attention is justified by the enormous negative impact that this disorder has on health, as well as on economic and social well-being. Governmental and other sources of research support have promoted substantial investigation into the negative consequences of alcohol, examining both animal models and human subjects. Consequently, there has been a virtual explosion of preclinical and clinical data, much of it focused on alcohol's pharmacologic effects. However, there have been few efforts to integrate this...

Eighty years have passed since Arthur Heffter, the founder of this handbook series, invited in 1913 eminent scientists from different parts of the world to contribute. At that time 6-10 years were needed to publish the first two volumes, which appeared between 1919 and 1923. During these 80 years, pharmacology as an independent science has undergone tremendouus development, which is reflected truly and com- prehensively by the ever-growing number of volumes in the now "classic" series of Heffter-Heubner's Handbook of Experimental Pharmacology. The Editorial Board of distinguished, world wide...

The toxicology of metals has been concerned in the past with effects that produced clinical signs and symptoms. However, this view of metal toxicology has expanded in recent years due principally to two advances. There has been a considerable increase in our knowledge of the biochemical effects of metals. In addition, biomarkers of toxicity can now be recognized that identify toxicity at levels of exposure that do not produce overt clinical effects. Thus, the toxicology of metals is now focused on nonclinical events that reflect adverse health effects. This new awareness has produced the...

The first edition of this handbook appeared exactly twenty-five years ago. Due to enormous changes in the area of diuretics, the second edition has had to be completely revised. Substantial progress has been made in the functional anatomy of the kidney and in the concepts of how substances and ions are specifically transported across the various nephron segments. No one could have foreseen twenty-five years ago that the late 1980s and the early 1990s have provided us with methodologies to study transport events not only at the single cell level, but even at the level of the single transporter...

It has been over 30 years since the first clinically important member of the quinolone class, nalidixic acid, was introduced into medical practice. The modification produced in the quinolone nucleus by introducing a fluorine at the 6-position led to the discovery of the newer fluoroquinolones with enhanced antibacterial activities as compared to nalidixic acid. By now a great deal of preclinical and clinical experience has been obtained with these agents. The intense interest in this class of antibacterial agents by chemists, micro- biologists, toxicologists, pharmacologists, clinical...

The immune system is the only organ system in the body besides the central nervous systems endowed with memory. Both types of memories are specific and long-lasting, sometimes life long. This memory capacity of the immune system provides the basis for the most cost-efficient of all medical interventions, successful vaccinations against many common infectious diseases. Such a success requires the isolation of the infectious agent or toxic substance, methods to grow and/or purify the relevant antigen and change it into something innocuous whilst maintaining its immunogenicity. Whereas the early...

In 1985, volume 74 of the Springer-Verlag Handbook of Experimental Phar- macology, under the editorship of H. -H. Frey and D. Janz, appeared. In this volume the then available data on the topic of antiepileptic drugs were col- lated and analysed. Over the intervening years knowledge in this area has grown progressively. More new antiepileptic drugs than the total number of agents that were in common use 15 years ago have in the interval either come on to the market or are about to do so. As well, further agents are at a fairly advanced stage of development, whilst the already established...

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.