Following the success of the first edition, published in 1995, this fully rewritten A Guide to Clinical Drug Research - Second Edition has been adapted to the most recent guidelines and developments in the field. It continues to provide a wealth of practical advice, ranging from the conception of an idea, planning a study and writing a protocol, through to the conduct of a study, data collection and analysis, and publication. It tells investigators what information they should expect sponsoring companies to provide, particularly when there is only limited information available about a new drug. It also explains what the company can expect of investigators, including the requirements of good clinical practice'. Unlike other currently available texts on clinical trials and pharmaceutical medicine, A Guide to Clinical Drug Research concentrates on the needs of the practising clinician and research team. It is not restricted to drug investigation, and is relevant to all those involved in clinical research in a variety of settings. Audience: Required reading for clinical researchers and others involved as investigators in a drug project, often sponsored by a pharmacuetical company, plus agents of the sponsoring companies themselves.

Polymers continue to show almost amazing versatility. We have always known that polymers could be used for trinkets, toys and dishes. Now, however, we are no longer surprised to encounter these adaptable mate rials in almost every place we look. We find them in our cars, tools, electronic devices, building materials, etc. The use of polymeric mate rials in medicine is also well documented in previous books by one of the Editors (Gebelein) and by others. Likewise, the use of polymeric mate rials in pharmaceutical applications, especially in controlled release systems, is also well established. Nevertheless, the use of these ubiquitous chemicals is far less ob vious in the field of cosmetics, although modern cosmetic preparations rely heavily on polymers and this trend is certain to increase. This book brings together much of the basic information on polymers in cosmetics and compares this usage with similar applications in pharmaceutical and medical applications. Cosmetics, like medicine and pharmacy, dates back to antiquity. We can find uses of perfumes, balms and ointments in various old books, such as the Bible. For example, the use of ointments and balms is noted more than thirty eight times, and perfumes and related materials are cited at least twenty nine times in the Bible."

Hypericum extract preparations are used extensively in many countries to treat mildly to moderately depressed patients. While this was based previously on traditional experience, extensive research over the last 10 years has given a broad preclinical and clinical basis to justify the use of Hypericum as an antidepressant. This book reviews the available data related to the biochemical, functional, and behavioural pharmacology of Hypericum and its active constituents. The clinical chapters overview the evidenced basis for its use as an antidepressant, initial data in anxiety and somatoform disorders, and the site effect profile of Hypericum and its possible relevant drug interactions. The known pharmacokinetics of the relevant constituents and the biopharmaceutical quality of commercially available Hypericum preparations are also discussed.

In Clinical Pharmacology of Cerebral Ischemia, a distinguished international panel of authors define our current understanding of neuronal damage after ischemia and critically review the significant recent progress in cerebrovascular accident (CVA) drug trials, both for animal models and in the clinical setting. These leading basic science and medical authorities survey such important new drugs as calcium-influx inhibitors, free-radical scavenging drugs, glutamate and glycinergic antagonists, and immune suppressors. They also evaluate all the latest findings concerning calcium homeostasis, glutamate toxicity, gene activation, and the role of free radicals, glycine, and hormones. Chapters devoted to the neuroimaging of stroke, clinical trials, and the role of cerebral immune activation complete this informative collection of cutting-edge reviews.

Recent years have seen enormous advances in the field of protein and peptide engineering and a greater understanding in the way in which biological response modifiers function in the body. It is now possible through the use of recombinant DNA techniques, or by solid phase protein synthesis, to produce significant quantities of a wide variety of regulatory agents that are therapeutically applicable. The list of these response modifiers expands almost daily to include interferons, macrophage activation factors, neuropeptides and agents that may have potential in cardiovascular disease, inflammation, contraception etc. Prospects to use some of these materials in medicine have reached the stage where products have either been approved by regulatory authorities or are the subject of applications as investigatory drugs or as new therapeutic agents. In some uses the pertinent agent will be administered on an acute basis in the form of a simple injection, as, for example, the use of a tissue plasminogen activator for the treatment of coronary infarct. In other cases regulatory proteins and peptides are indicated for chronic therapy and here they will need to be administered by an appropriate delivery system. Unfortunately, the research on delivery systems for peptides and proteins has not kept pace with the rapid progress in biotechnology and, consequently, there are presently few systems that are entirely appropriate for the administration of macromolecular drugs according to complex dosage regimens, (eg intermittent and pulsed therapy). Furthermore essential pharmacokinetic and pharmacodynamic data may be missing.

This detailed book arrives as there is an increasing need for multiplex biomarker readouts for improved clinical management and to support the development of new drugs by pharmaceutical companies, due to continuous technical developments and new insights into the high complexity of many diseases. Chapters explore the basic technology platforms being applied in the fields of genomics, proteomics, transcriptomics, metabolomics, and imaging, which are currently the methods of choice in multiplex biomarker research. The book also describes the chief medical areas in which the greatest progress has been made and highlight areas where further resources are required. Written for the highly successful Methods in Molecular Biology series, methodology chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Multiplex Biomarker Techniques: Methods and Applications serves as an ideal resource for a wide variety of researchers interested in these vital multiplex techniques.

This book arises from a workshop organized by the American Association of Pharmaceutical Scientists entitled "Optimizing the Drug-Like Properties of Leads in Drug Discovery," which took place in Parsippany, NJ in September 2004. The workshop focused on the optimization of the drug-like properties of leads in drug discovery. The volume outlines strategies and methodologies designed to guide pharmaceutical and biotechnology companies through the drug discovery and development process.

The pace of new research and level of innovation repeatedly introduced into the field of drug delivery to the lung is surprising given its state of maturity since the introduction of the pressurized metered dose inhaler over a half a century ago. It is clear that our understanding of pulmonary drug delivery has now evolved to the point that inhalation aerosols can be controlled both spatially and temporally to optimize their biological effects. These abilities include controlling lung deposition, by adopting formulation strategies or device technologies, and controlling drug uptake and release through sophisticated particle technologies. The large number of contributions to the scientific literature and variety of excellent texts published in recent years is evidence for the continued interest in pulmonary drug delivery research. This reference text endeavors to bring together the fundamental theory and practice of controlled drug delivery to the airways that is unavailable elsewhere. Collating and synthesizing the material in this rapidly evolving field presented a challenge and ultimately a sense of achievement that is hopefully reflected in the content of the volume.

In the literature, several terms are used synonymously to name the topic of this book: chem-, chemi-, or chemo-informatics. A widely recognized de- nition of this discipline is the one by Frank Brown from 1998 (1) who defined chemoinformatics as the combination of "all the information resources that a scientist needs to optimize the properties of a ligand to become a drug. " In Brown's definition, two aspects play a fundamentally important role: de- sion support by computational means and drug discovery, which distinguishes it from the term "chemical informatics" that was introduced at least ten years earlier and described as the application of information technology to ch- istry (not with a specific focus on drug discovery). In addition, there is of course "chemometrics," which is generally understood as the application of statistical methods to chemical data and the derivation of relevant statistical models and descriptors (2). The pharmaceutical focus of many developments and efforts in this area-and the current popularity of gene-to-drug or si- lar paradigms-is further reflected by the recent introduction of such terms as "discovery informatics" (3), which takes into account that gaining kno- edge from chemical data alone is not sufficient to be ultimately successful in drug discovery. Such insights are well in accord with other views that the boundaries between bio- and chemoinformatics are fluid and that these d- ciplines should be closely combined or merged to significantly impact b- technology or pharmaceutical research (4).

Psychopharmacology may be defined as the study of the effects of drugs on behavior. As an established scientific discipline, this is a relatively new area of research. Despite its short history, however, psychopharmacology has achieved a considerable degree of sophistication in the variety of experi mental approaches that are currently employed. Consequently, the interpretation of data accumulated through the use of various experimental laboratory techniques has become increasingly difficult and complex. Numerous excelIent texts and review articles are available that serve to outline recent progress in psychopharmacology (particularly the Handbook of Psychopharmacology series, edited by L. L. Iversen, S. D. Iversen, and S. H. Synder). Volumes such as these serve to usefully review the available litera ture without attempting a critical appraisal of the utility and limitations of methods and the difficulties of interpreting empirical data. Such conceptual and methodological problems are now an issue of paramount importance in studying the behavioral effects of drugs. The present volume can be regarded as a "conceptual cookbook" that examines the utility and limitations of various experimental approaches commonly taken in psychopharmacology. This practically oriented text should prove particularly useful for pharmacologists and neurochemists who have no formal training in behavioral research and require an intro duction to the actuallaboratory practice of the field. In addition, the useful and informative treatment of current issues in psychopharmacology will undoubtedly appeal to the majority of active researchers."

This compelling volume provides a broad and accessible overview on the rapidly developing field of social neuroscience. A major goal of the volume is to integrate research findings on the neural basis of social behavior across different levels of analysis from rodent studies on molecular neurobiology to behavioral neuroscience to fMRI imaging data on human social behavior.

This book begins the discourse on post-trial access to drugs in developing countries. Underlying ethical issues in global health inequalities and global health research serve as the context of the debate. Due to rampant allegations of violations of rights of research participants, especially in developing countries, it discusses the regulatory infrastructure and ethical oversight of international clinical research, thus emphasizing the priority of safeguarding the rights of research participants and host populations as desiderata in conducting clinical trials in developing countries. This is the first book that analyzes the major obstacles of affordable access to drugs in developing countries - patent and non-patent factors and how they can be overcome through a middle ground approach and a new paradigm to establish global health justice which includes national and global health responsibilities. The book also deals extensively with all complex aspects of the discourse on affordable access to drugs in developing countries, including intellectual property law, international regulations, political and cultural systems, international trade agreements. Furthermore it contains a robust ethical debate and in-depth analysis. The book crafts a paradigm of global health justice involving a sliding scale of national and global responsibilities for the realization of the right to health in general and access to drugs in particular.

Immunopotentiators in Modern Vaccines, Second Edition, provides in-depth insights and overviews of the most successful adjuvants, those that have been included in licensed products, also covering the most promising technologies that have emerged in recent years. In contrast to existing books on the subject, the chapters here provide summaries of key data on the mechanisms of action of the individual vaccine adjuvants. In addition, the book covers key aspects of how the technologies might be further developed and what might be their limitations, while also giving an overview of what made the most advanced adjuvant technologies successful.

The many drawbacks of conventional dosage forms and delivery systems are overcome by designing and developing controlled release drug delivery systems, and pharmaceutical and other scientists have carried out extensive and intensive investigations in the field to explore their applications. A controlled-release drug formulation can improve product efficacy and extend patent protection. As controlled drug delivery systems continue to play a vital role in delivering various types of therapeutic agents in a controlled manner, researchers are only just scratching the surface of their full potential. Advancements in Controlled Drug Delivery Systems supplies information on translating the physicochemical properties of drugs into drug delivery systems, explores how drugs are administered via various routes, and discusses recent advancements in the fabrication and development of controlled drug delivery systems. It also underlines the methodology of controlled drug delivery system preparation and the significance, disadvantages, detailed classifications, and relevant examples. Covering topics such as machine learning and oral-controlled drug delivery, this book is ideal for pharmacists, healthcare professionals, researchers, academicians, research centers, health units, students, and pharmaceutical and scientific laboratories.

This detailed volume assembles comprehensive protocols to assist with the study of structural, molecular, cell biological, and in vivo facets of GPCRs, and to enable the development of experimental tools for screening novel GPCR drugs. Sections explore the tweaking of ligands, bioluminescence and FRET approaches, specific GPCR signaling properties, as well as visualization of subcellular compartmentalization. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, G Protein-Coupled Receptor Signaling: Methods and Protocols serves as an ideal reference for life scientists working in a variety of research fields including molecular pharmacology, cell and developmental biology, brain behavior and physiology, drug development and screening. Chapter 4 is available open access under a CC BY 4.0 license via link.springer.com.

Efforts to describe and model the molecular structure of biological membranes go back to the beginning of the last century. In 1917, Langmuir described membranes as a layer of lipids one molecule thick [1]. Eight years later, Gorter and Grendel concluded from their studies that "the phospholipid molecules that formed the cell membrane were arranged in two layers to form a lipid bilayer" [2]. Danielli and Robertson proposed, in 1935, a model in which the bilayer of lipids is sequestered between two monolayers of unfolded proteins [3], and the currently still accepted fuid mosaic model was proposed by Singer and Nicolson in 1972 [4]. Among those landmarks of biomembrane history, a serendipitous observation made by Alex Bangham during the early 1960s deserves undoubtedly a special place. His fnding that exposure of dry phospholipids to an excess of water gives rise to lamellar structures [5] has opened versatile experimental access to studying the biophysics and biochemistry of biological phospholipid membranes. Although during the following 4 decades biological membrane models have grown in complexity and functionality [6], liposomes are, besides supported bilayers, membrane nanodiscs, and hybrid membranes, still an indisputably important tool for membrane b- physicists and biochemists. In vol. II of this book, the reader will fnd detailed methods for the use of liposomes in studying a variety of biochemical and biophysical membrane phenomena concomitant with chapters describing a great palette of state-of-the-art analytical technologies.

In transfusion medicine the scientific fundamentals of immunology have had a considerable clinical impact. Transfusion may suppress the immunity but some patients could suffer disadvantages including GvHD, alloimmunisation and possible cancer, where white cells (WBC) play pivotal roles in this phenomenon, presenting antigens and producing cytokines. A clinical application of this practice is LAK-cells targeted against cancer. MHC on the WBC may provide additional immunological modulations through series of secondary messengers. Thus reduction of WBC in the blood and bone marrow may be advantageous for patients. On the other hand, sharing a part of MHC or making the transplanted white cells anergic by storage may be even more advantageous for patients. CMV infection could mimic part of this MHC. UV radiation is effective in the inactivation of the WBC although filters are easy means for such removal. However, their accurate quantification requires flow cytometry that has considerable potential application in blood transfusions. Idiotypic antibody could play an important role in platelet theory. However, the potential infection risks in transfusion like HIV and HCV remain, but application of molecular biological methods like PCR or RT/PCR has great potentials in detection of infectious diseases, transplantation and genetic disorders. Immuno affinity purified concentrates, like factor IX and protein C, could reduce patients' immune functions, where in the future protein C could be derived from transgenic animals. Advances are sure to emerge through adoptive immunotherapy and gene therapies are exciting prospects when genes transferred into lymphocytes could be used to correct cell mediated immune deficiency, as in ADA.

This book serves as a reference volume for anyone interested in nicotine and tobacco. An international team of authors contribute to this comprehensive review of current knowledge on the pharmacokinetics and metabolism of nicotine. A broad range of material on the action and uptake of nicotine and the consequences of exposure to it has been drawn together for the first time in this volume. This book should be of interest to research scientists and health professionals in pharmacology, toxicology and neurosciences.

The specific topic, "Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants - New Perspectives In Parkinson`S 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., Parkinson`s 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.

Valproic acid was first synthesized in 1882 by Burton, but there was no known clinical use until its anticonvulsant activity was fortuitously discovered by H. Meunier in 1963 in the laboratory of G. Carraz. The first clinical trials of the sodium salt of valproate were reported in 1964 by Carraz. It was marketed in France in 1967 and was released in the United States in 1978 for the treatment of epilepsy. Since then, valproate has established itself worldwide as a major antiepileptic drug against several types of seizures. Clinical experience with valproate has continued to grow in recent years, including use of valproate for diseases other than epilepsy, for example in bipolar disorders and migraine. In this book, emphasis is placed on the scientific background leading to the discovery of valproate and its clinical development into one of the most widely and successfully used antiepileptic drugs, a real milestone in drug therapy. The current state of knowledge of valproate is reviewed by experts in the field, including new hypotheses on its mechanisms of action, its metabolism into pharmacologically active metabolites, its unique distribution characteristics, its undesirable hepatotoxic and teratogenic adverse effects, and its various clinical uses. The monograph is aimed at a broad readership, particularly neurologists, psychiatrists and basic scientists working in the field of epilepsy research. Furthermore, the book also deals with structure-activity relationships of valproate as well as of its metabolites and analogs and should therefore attract researchers working in medicinal chemistry.

Founded in 1959 by its current Editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

What drives a scientist to edit a book on a speci c scienti c subject such as chiral mechanisms in separation methods? Until December 2005, the journal Analytical Chemistry of the American Chemical Society (Washington, DC) had an A-page section that was dedicated to simple and clear presentations of the most recent te- niques or the state of the art in a particular eld or topic. The "A-page" section was prepared for a broad audience of chemists including industrial professionals, s- dents as well as academics looking for information outside their eld of expertise. 1 Daniel W. Armstrong, one of the editors of this journal and a twenty-year+ long friend, invited me to present my view on chiral recognition mechanisms in a simple and clear way in an "A-page" article. In 2006, the "A-page" section was maintained as the rst articles at the beginning of each rst bi-monthly issue but the pagination was no longer page distinguished from the regular research articles published by the journal. During the time between the invitation and the submission, the A-page section was integrated into the rest of the journal and the article appeared as (2006) Anal Chem (78):2093-2099.