Cardiac Drug Development Guide outlines, in detail, the therapeutics of cardiac medicine currently at the cutting edge of scientific research and development around the world. This volume integrates basic and clinical cardiac pharmacology by c- bining, for the first time, both classical and molecular aspects of therapeutic drug development. The chapters comprise a broad spectrum of therapeutic areas and hence involve a comprehensive discussion of molecular, biochemical, and electrophy- ological concepts based on years of in vitro as well as in vivo pharmacological st- ies. In addition, the latter part of the book includes comprehensive clinical cardiac chapters that describe important topics in molecular medicine. These chapters also discuss current clinical therapeutic trends in medicine and provide an evaluation of the efficacy of novel drugs in these areas. Cardiac Drug Development Guide has many distinctive and outstanding features that set it apart from other cardiac pharmacology books. This book introduces topics in an easily understandable format for researchers in many varying disciplines by integrating and thereby simplifying concepts not usually discussed across a broad range of cardiac disciplines and in a highly technical field. Each chapter not only introduces and describes the physiology, pharmacology, and pathophysiology of the disease, but also overviews the clinical implications of drug development, what stages these areas are currently in, and also reviews some of the methodologies involved in drug discovery and development. As a result, this book provides a comprehensive overview of the most advanced procedures in cardiac pharmacology today.

The specific topic, Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants New Perspectives In ParkinsonS Disease Therapy, was chosen in light of accumulating neurobiological evidence indicating that, in addition to exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP]), endogenous compounds may play an important role in the most common neurodegenerative disorders (e.g., Parkinsons disease). Two groups of amine related compounds, which appeared chemically like MPTP, were detected in human brain and cerebrospinal fluid (CSF): "ss"-carbolines (BCs) and tetrahydroisoquinolines (TIQs). These are heterocyclic compounds formed endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a wide spectrum of psychopharmacological and behavioral effects. The TIQs and BCs may bind to their own high affinity sites on neuronal membranes associated with or located close to the receptors of neurotransmitters. Research on TIQs and BCs is stimulated also by their possible role in pathological conditions, especially parkinsonism and alcoholism. Recently, clinical interest has been spurred by their role as neuroprotective, and even neurorestorative, anticonvulsant and antiaddictive, substances.

In this book we are going to summarize, for the first time, the results from behavioral, neurochemical and molecular experiments, which demonstrate a wide spectrum of TIQs and BCs effects - from their rather mild neurotoxic actions to the important neuroprotective and antiaddictive properties.

Additionally, the recent results of experimental studies "in vivo" have allowed a much better understanding and simultaneous comparison of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic actions of endogenous TIQs and BCs and have pointed to the possibility of their therapeutic applications in neurodegenerative diseases such as Parkinson's disease."

Biologics have revolutionised the treatment of many severe conditions, delivering exceptional clinical results but also producing exceptionally high prices. As patents expire, copies and price competition are expected throughout the world. However, due to the intrinsic heterogeneity and molecular complexity of biologic medicinal products, their copies cannot simply be authorized under the "generic rule" valid for small chemical entities. In response, a dedicated regulation was issued in the European Union. It is based on the concept of "biological medicinal products similar to a biological reference product", or "biosimilars". This book analyses the context of biotechnological production and addresses the European legal framework for biosimilar market approval. It highlights post-market authorisation issues, such as Risk Management Plans and substitution of products, and outlines some other issues, such as cost management and international nomenclature. This book is primarily intended for hospital-based physicians and pharmacists. It will also be a valuable resource for all actors from all countries who want to better understand the emergence of these new medicinal products within the European context.

In the late 1980s, Peptide Societies were established in Europe, the United States, and Japan, and more recently, in the Asian and the Pacific Rim regions including Australia, China, and Korea. At the time of the establishment of the American, European and Japanese Peptide Societies, the International Liaison Organizing Committee representing these Peptide Societies, along with the Australian Peptide Society, began discussions for holding international confer ences which would supercede or be held in lieu of the numerous individual meetings, held by the peptide societies of each individual country or region. The representative of the Chinese Peptide Society participated in these discus sion in the International Liaison Organizing Committee at the meeting of the American Peptide Symposium in Nashville, in June 1997. After lengthy discus sions over several years, we agreed to organize and host the International Peptide Symposium in Japan. The First International Peptide Symposium (IPS'97) was held on November 30-December 5, 1997, in Kyoto, and was co sponsored by four Peptide Societies. The attendance at this Symposium was 550 participants, including representatives from 32 different countries. We were very pleased with this outcome and anticipate an even larger attendance for forthcoming Symposia in future years. The revolution and advances in science and technology during the past two decades has caused traditional peptide chemistry to expand to peptide science, spreading from physical science to biology, pharmacology, and medicine.

A comprehensive treatment of the characterisation techniques used in investigating inorganic and organic molecules that interact with biomolecules is presented to the reader in a clear fashion. The work consists of two parts: (i) synthetic aspects of metallointercalators along with targeting and improving transport and (ii) the various techniques that are used for probing their interactions, such as; DNA-NMR, PGSE-NMR, DNA ESI-MS, Linear and Circular Dichroism, Fluorescence Spectroscopy, Confocal Microscopy, Viscosity, TGA and dialysis, Microarrays, biological analysis. Chapters are devoted to the synthesis and the techniques used to study the interactions of inorganic complexes with biomolecules. Considerably detailed examples are used to help illustrate the application of these techniques. This book is a useful resource for an array of inorganic and organic advanced undergraduate and graduate courses and for researchers in drug discovery.

Phytochemicals from medicinal plants are receiving ever greater attention in the scientific literature, in medicine, and in the world economy in general. For example, the global value of plant-derived pharmaceuticals will reach $500 billion in the year 2000 in the OECD countries. In the developing countries, over-the-counter remedies and "ethical phytomedicines," which are standardized toxicologically and clinically defined crude drugs, are seen as a promising low cost alternatives in primary health care. The field also has benefited greatly in recent years from the interaction of the study of traditional ethnobotanical knowledge and the application of modem phytochemical analysis and biological activity studies to medicinal plants. The papers on this topic assembled in the present volume were presented at the annual meeting of the Phytochemical Society of North America, held in Mexico City, August 15-19, 1994. This meeting location was chosen at the time of entry of Mexico into the North American Free Trade Agreement as another way to celebrate the closer ties between Mexico, the United States, and Canada. The meeting site was the historic Calinda Geneve Hotel in Mexico City, a most appropriate site to host a group of phytochemists, since it was the address of Russel Marker. Marker lived at the hotel, and his famous papers on steroidal saponins from Dioscorea composita, which launched the birth control pill, bear the address of the hotel."

This volume attemptsto provide the formulation scientist with casehistories involving the use of therapeutic proteins and peptides that have been mar- keted or are under clinical testing. In previous volumes of this series,funda- mental theories and principles ofprotein characterization and stability were presented in depth by researchers in their fieldsofexpertise. The way from theory to practice isnot alwaysobvious and straightforward. There isa need for practical examples of how the principles and theories are put into use, specificallyin the development of a pharmaceutical product. It is our hope that this volume will fulfillsuch a need. Itisnot asimple task to choose a panel ofproteinsand peptides from the over 200 agents in human clinical trials. We have tried to collect a wide representation of molecules of different sizes-from 10 amino acids (Leu- prolide) to 1020 amino acids (Muromonab CD3). The examples include agents derived from various sources including monoclonal antibodies (Mur- omonab CD3), recombinant DNA (human and bovine growth hormones), natural source (fibrolase), and chemical synthesis (Leuprolide). Clearly this list is not intended to be encyclopedic. It isthe first time a collection of this sort has been made accessibleto the formulation scientists involved in devel- oping protein and peptide products. Although each chapter in this volume focuses primarily on the charac- terization and stability of a specific molecule, each has unique aspects.

Proteins are still gaining importance in the pharmaceutical world, where they are used to improve our arsenal of therapeutic drugs and vaccines and as diagnostic tools. Proteins are different from "traditional" low-molecular-weight drugs. As a group, they exhibit a number of biopharmaceutical and formulation problems. These problems have drawn considerable interest from both industrial and aca demic environments, forcing pharmaceutical scientists to explore a domain previ ously examined only by peptide and protein chemists. Biopharmaceutical aspects of proteins, e.g., low oral bioavailability, have been extensively investigated. Although all possible conventional routes of ad ministration have been examined for proteins, no real, generally applicable alter native to parenteral administration in order to achieve systemic effects has yet been discovered. Several of these biopharmaceutical options have been discussed in Volume 4 of this series, Biological Barriers to Protein Delivery. Proteins are composed of many amino acids, several of which are notorious for their chemical instability. Rational design of formulations that optimize the native structure and/or bioactivity of a protein is therefore of great importance when long shelf life is required, as it is for pharmaceutical products. This issue has also been examined in two prior volumes of this series: Volume 2: Stability of Protein Pharmaceuticals (Part A) and Volume 5: Stability and Characterization of Protein and Peptide Drugs.

Proceedings of a conference sponsored by the American Association of Pharmaceutical Scientists, the U.S. Food and Drug Administration, and the American Society for Clinical Pharmacology and Therapeutics, held in Arlington, Virginia, April 24-26, 1991

''A wealth of information...these two volumes will be immensely valuable to anyone having to deal with this difficult group of compounds.'' ---Biochemical Systematics and Ecology, from a review of Saponins Used in Traditional and Modern Medicine and Saponins Used in Food and Agriculture

This 1984 book, part of the series Progress in Clinical Pharmacy, provides an authoritative account of developments in clinical pharmacy in Europe. It is prefaced by chapters on the American experience in clinical pharmacy education and on patient education. The book reports the proceedings of the twelfth European symposium on clinical pharmacy, held in Barcelona in October 1983. Two of the great challenges facing pharmacy were how better to educate pharmacists to fulfil a clinical or extended role in healthcare and how to meet an important part of such a role, that is the better education of patients in the use of medicines. These two complementary topics were the twin themes of this symposium. As well as papers on these themes, other articles on clinical pharmacy were presented and are published in these proceedings. The book will continue to interest any pharmacist contemplating the development of clinical pharmacy.

This 1983 book reports the proceedings of the eleventh European symposium on clinical pharmacy which was held in Brussels in October 1982. The theme of the symposium was the concept of the therapeutic team and the relative contributions and responsibilities of pharmacists, nurses and physicians to the planning and implementation of drug treatment regimens. The first section of the volume provides an introduction to the concept of the therapeutic team and reflects the views several medical professionals. The later sections cover the practice of the therapeutic team in parenteral nutrition, oncology, dermatology, epilepsy, internal medicine, nuclear medicine and drug selection. Not only did this book review achievements and experiences in clinical pharmacy, but it also looked towards the future of clinical pharmacy development in Europe. It will still be of significant interest to clinical pharmacy specialists today.

production of this volume of the Handbook. If this joint enterprise has succeeded it is thanks to their competence, knowledge and application, for the editor's role is merely that of a coordinator. My thanks are also due to Springer-Verlag, the publishers, who gave me every possible assistance in seeing this volume to completion. Dr. D. Maroske was kind enough to prepare the Subject Index. And lastly I should like to voice my indebtedness to the Management of Sandoz Ltd., Basle, which allowed me to devote a not inconsiderable part of my time to the editing of this volume. I am also very grateful to a number of members of the staff of Sandoz Ltd.: to Mr. J.E. Smith, B. Sc., F.1. L., who translated some chapters and revised the language of others and to Miss Hannelore Straube and Miss Sonja Ebner for their valuable secreterial help.

Animal cell technology is becoming an increasingly important part of biotechnology and many products are now used in human health care and for veterinary applications. However, there are many times more products actually in the developmental pipelines of the biotechnology industry, including various phases of clinical trials. The Proceedings of the 15th Meeting of the European Society for Animal Cell Technology (Tours, France, September 1997) presents the actual current state as well as New Developments and Applications in Animal Cell Technology for the benefit of society. These Proceedings represent both the current state and applications of animal cell technology and the way the technology is expanding into new areas to give a unique insight into new products and applications for human and animal health care.

Even high-speed supercomputers cannot easily convert traditional two-dimensional databases from chemical topology into the three-dimensional ones demanded by today's chemists, particularly those working in drug design. This fascinating volume resolves this problem by positing mathematical and topological models which greatly expand the capabilities of chemical graph theory. The authors examine QSAR and molecular similarity studies, the relationship between the sequence of amino acids and the less familiar secondary and tertiary protein structures, and new topological methods.

Drug products are complex mixtures of drugs and excipients and, as such, their chemical and physical stability kinetics are complex. This book discusses the stability of these dosage forms with preformulation studies through to the studies on the final products. The book is intended for graduate students, researchers and professionals in the field of Pharmaceutics and Pharmaceutical Chemistry.

Proceedings of the International Symposium on Polymer Therapeutics - Recent Progress in Clinics and Future Prospects, held July 13-14, 2001, in Nara, Japan. The technology of polymer science has developed considerably during the past half-century, and this volume describes some of the aspects of this technology that will have a great impact in the future. Among these advances, for example, are gene delivery to specific disease sites and carrier polymers that respond to a stimulus or particular environment. Cancer targeted drug delivery is another focused area of this volume because of the important nature of EPR-effect of polymer drugs in tumor. Included are discussions of as many examples as possible of polymer drugs that have achieved, or are close to clinical use. The concept of "Polymer drugs" here is limited to primarily injectable and water-soluble agents, although also covered are some drugs in micellar form or liposomes. This book is intended for students and researchers in the field of pharmacology who have particular interests in drug delivery, targeting, and formulation, as well as for clinicians such as oncologists who are interested in the field. People who work at regulatory agencies should also be aware such that drugs with great potential are being developed and will be beneficial to many patients, as well as to health insurance agencies because of improved cost effectiveness.

Self-assembly monolayer (SAM) structures of lipids and macromolecules have been found to play an important role in many industrial and biological phenomena. This book describes two procedures, namely the STM and AFM, that are used to study SAMs at solid surfaces. K.S. Birdi examines the SAMs at both liquid and solid surfaces by using the Langmuir monolayer method. This book is intended for researchers, academics and professionals.

It was an agreable, though strenuous task to edit a book with so many distin guished contributors, on a subject to which I have given half of my life. In 1959, when Prof. O. EICHLER invited me to edit a book on "Histamine and Anti histaminics", as a supplement to HEFFTER'S Handbuch, I thought the task could be done in three years. Now, five years are gone and only half is fulfilled. Though, so far as the "Histamine" part of the book is concerned, the initial plan has been followed very closely, we had to leave the Anti-histaminics for another volume of unpredictable dimensions. In 1924, eight pages inserted in a Chapter on M utterkorn, by ARTHUR R. CUSHING were considered enough, in vol. II, Part II, pg. 1319-1326, of the Handbuch. Now, 922 pages did not suffice to cover all the aspects of the subject. Especially in the last few years the subject has expanded in so many directions, that the antihistaminic part had to be excluded from the present volume. Possibly, another thousand pages will be necessary to cover what remains of the subject. In planning the book we made great use of the excellent and classical mono graph by W. FELDBERG and E. SCHILF on Histamin, published by Julius Springer, in 1930.

The aim and scope of this book is to highlight the sources, isolation, characterization and applications of bioactive compounds from the marine environment and to discuss how marine bioactive compounds represent a major market application in food and other industries. It discusses sustainable marine resources of macroalgal origin and gives examples of bioactive compounds isolated from these and other resources, including marine by-product and fisheries waste streams. In addition, it looks at the importance of correct taxonomic characterization."

Enhancing Medication Adherence: The Public Health Dilemma is a comprehensive guide to medication adherence for the healthcare professional. Clinicians and pharmacists alike can benefit from key opinion leader and author Hayden Bosworth s text as he explains the details and causes behind medication nonadherence as well as methods on how healthcare providers can determine if a patient is nonadherent. Additionally, Bosworth discusses various studies, which assess adherence, adherence-related technology, best practices for clinicians and pharmacists, and future directions and recommendations in the field."

High-throughput screening and combinatorial chemistry are two of the most potent weapons ever to have been used in the discovery of new drugs. At a stroke, it seems to be possible to synthesise more molecules in a month than have previously been made in the whole of the distinguished history of organic chemistry, Furthermore, all the molecules can be screened in the same short period. However, like any weapons of immense power, these techniques must be used with care, to achieve maximum impact. The costs of implementing and running high-throughput screening and combinatorial chemistry are high, as large dedicated facilities must be built and staffed. In addition, the sheer number of chemical leads generated may overwhelm the lead optimisation teams in a hail of friendly fire. Mother nature has not entirely surrendered, as the number of building blocks that could be used to build libraries would require more atoms than there are in the universe. In addition, the progress made by the Human Genome Project has uncovered many proteins with different functions but related binding sites, creating issues of selectivity. Advances in the new field of pharmacogenomics will produce more of these challenges. There is a real need to make hi- throughput screening and combinatorial chemistry into 'smart' weapons, so that their power is not dissipated. That is the challenge for modellers, computational chemists, cheminformaticians and IT experts. In this book, we have broken down this grand challenge into key tasks.