This comprehensive ebook covers all the aspects of ADME/PK modeling including solubility, absorption, formulation, metabolic stability, drug-drug interaction potential and a special delivery tool of drug candidates. The book provides an integrated view of fundamental ADME issues and challenges in early drug development from the aspect of practicing drug researchers. It also provides valuable help for the medicinal chemist in the process of multiple optimization.

Thermodynamics and kinetics (i.e., chemical interactions) are extremely important concepts for pharmaceutical scientists to understand since the “drug selection process”, that is, the process used by pharmaceutical companies to discover and develop marketable drugs, is totally dependent upon these theories. While both theories are important, kinetic models describing complex chemical and biological processes provide a unifying theory for all phases of the discovery and development of drugs. Unfortunately, in most textbooks the mathematical descriptions necessary to develop a deeper understanding of kinetic models are omitted. This is primarily done such that the underlying chemistry and biochemistry principles are not obscured by the “mathematical maze” that is generated from these models. As a result many chemists and biologists veer rapidly away from thermodynamics and kinetics. For some scientists, this can lead to confusion on how to apply these models to real-life situations. For example, many enzyme kinetic models are formulated as rate equations. Since experimentally measurements typically determine concentrations and rarely determines rates directly, confusion arises on how to apply kinetic models. In this case, either the model is integrated to give a description of the concentration course of the enzyme reaction or the data is differentiated (i.e., the process of determining rates) by measuring tangents to the reaction curves at zero time. The level of mathematical skills required to solve kinetic models is minimal for anyone who has studied college level algebra and calculus. Thus, the objective of this book is to present a brief review of thermodynamics and kinetics followed by a detailed step-by-step approach in developing and solving kinetic models for complex chemical and biological processes. The book focuses on building a solid mathematical foundation of enzyme kinetic models by systematically evolving simple uni- and bi-molecular models to enzyme models. Applications for some of these kinetic models are generated from pharmaceutical examples and a selection of problems is presented at the end of each chapter. This elementary approach has been intentionally selected to keep the book at a self-explanatory level. It is anticipated that the reader will be able to follow the mathematical operations and in the process develop a deeper understanding of kinetic models and an improved ability to interpret kinetic parameters. The book is restricted to solution chemical kinetics and does not deal with the theories of chemical reactions, gas-phase reactions, experimental kinetic methods and so on. There are many excellent chemical kinetic textbooks available for those interested in these topics. The solution chemical kinetics materials for the book were obtained from literature papers and several books on physical chemistry and enzyme kinetics. The ideas from these sources have been hopefully reinterpreted in a style that is well matched to those pharmaceutical scientists that do not have a comprehensive knowledge of kinetic models and the mathematical skills to solve them. Chapter 1 presents a general overview to thermodynamic and kinetic principals and theory. In Section i, an overview to the scope of the book is presented. A brief review of mathematical fundamentals used in the book (Section ii) and kinetic and thermodynamic principals are present (Section iii and iv). A glossary of symbols and abbreviation used throughout the book is presented in Section v. Chapter 2 describes the basic theory of first-order kinetic models. These types of mathematical models are used for irreversible (Section I) and reversible (Section II) rearrangement reactions and some examples are presented to illustrate their applications to drug discovery. Chapter 3 describes second-order irreversible (Section III) and reversible (Section IV) dimerization reactions while Chapter 4 describes second-order irreversible (Section V) and reversible (Section VI) binding reactions. Chapter 5 describes partially and fully coupled reversible completive binding reactions (Section VII). Chapter 6 describes second-order kinetic models that are used to analyze consecutive irreversible (Section VIII) and reversible (Section IX) substrate suicide enzyme reactions. Chapter 7 describes kinetic models that are used to analyze consecutive irreversible (Section X) and reversible (Sections XI and XII) enzyme reactions. Chapter 8 describes kinetic models that are used to analyze consecutive reversible inhibition enzyme reactions (Section XIII - XVI). Chapter 9 describes kinetic models that are used to analyze substrate (Section XVII) and product inhibition (Section XVIII) enzyme reactions. The Appendix contains the answers to the problems.

Contemporary Sleep Medicine should be of interest to a large number of readers interested in sleep medicine. It is divided into two parts – one for patients or simple readers and another for physicians or advanced readers. The Ebook explores new research grounds for sleep disorders. These include novel methodologies for epidemiological research and strategies for curing individuals who suffer from sleep disorders. The volumes seek to update interested readers on the latest advances in the uncharted territory of sleep medicine.

Since the last century, remarkable advances at both the basic and clinical levels have considerably improved our ability to evaluate and treat children with neurological disorders. Many cases seen by general pediatricians are primarily neurological accounting for up to 30% of all consultations to pediatrics with a high ratio of follow-up visits to new patients of about 3:1. This manual is a neurology reference for medical students and pediatric residents and is intended to supplement larger textbooks on pediatric neurology already available. Many of undergraduate medical students refer to deficient and oversimplified references that do not enable them to deal with pediatric neurology patients adequately. The manual presents a simplified, organized, and comprehensive problem based approach to common pediatric neurological disorders directed to the level of medical students, pediatric residents, general practitioners and general pediatricians. This e-book is thus a concise outline with practical tips to facilitate proper diagnosis and management of various neurological disorders.

This e-book is a reference on Selegiline/(-)-Deprenyl effects on the brain. Selegiline, described in thousands of research papers, is registered in over 60 countries. At present, more than one hundred preparations containing selegiline circulate in the global market under different brand names. They are widely used in the treatment of Parkinson’s disease, Alzheimer’s disease, major depression and as a geroptotective / anti-aging drug. (-)-Deprenyl/selegiline, the first selective inhibitor of B-type MAO which, in contrast to the known MAO inhibitors, did not potentiate the effect of tyramine but inhibited it. The compound could be combined with levodopa in Parkinson’s disease without signs of hypertensive reactions. The DATATOP study in the USA revealed that (-)-deprenyl delayed the onset of disability associated with early, otherwise untreated Parkinson’s disease. The age-related decay of the supply of the brain with phenylethylamine ( PEA), due to the progressive increase of MAO-B activity in the aging brain, and dopamine, due to the better than average decline of the dopaminergic neuronal activity during the postdevelopmental phase of life, are irresistible biochemical lesions of aging. The speed of deterioration of behavioral performances with the passing of time and longevity depends significantly on the pace of the worsening of these leasions. (-)-Deprenyl, Increasing the supply of the brain with PEA and dopamine, counteracts this aging process. Maintenance of male rats from sexual maturity until death on (-)-deprenyl delays the age-related loss of the capacity to ejaculate, slows the age-related decline of learning ability and prolongs life. In humans, maintenance from sexual maturity on (-)-deprenyl (1 mg daily) is, for the time being, the most promising prophylactic treatment to fight against the age-related decay of behavioral performances, prolonging life, and preventing or delaying the onset of age-related neurodegenerative diseases such as Parkinson’s and Alzheimer’s. This e-book is a useful reference for graduate medical students, academic researchers in the field of neuropsychopharmacology, neurophysiology and gerontology and professional research groups in commercial organizations manufacturing selegiline preparations.

Frontiers in Clinical Drug Research - CNS and Neurological Disorders is an eBook series that brings updated reviews to readers interested in advances in the development of pharmaceutical agents for the treatment of central nervous system (CNS) and other nerve disorders. The scope of the eBook series covers a range of topics including the medicinal chemistry, pharmacology, molecular biology and biochemistry of contemporary molecular targets involved in neurological and CNS disorders. Reviews presented in the series are mainly focused on clinical and therapeutic aspects of novel drugs intended for these targets. Frontiers in Clinical Drug Research - CNS and Neurological Disorders is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critical information for developing clinical trials and devising research plans in the field of neurology. The first volume of the series features 9 chapters that cover a variety of therapeutic areas such as: </p><p> -advances in the treatment of cerebral gliomas, multiple sclerosis and schizophrenia, </p><p> -different uses for antidepressants in treating drug users and adolescents suffering from depression, </p><p> -research on epilepsy and autism spectrum disorder therapy.

The endocannabinoid system comprises at least two G-protein-coupled receptors (the cannabinoid CB1 and CB2 receptors) activated by marijuana’s psychoactive principle ∆9-tetrahydrocannabinol (THC) and the endogenous ligands known as endocannabinoids. The apex of endocannabinoid research seems to have been reached with the clinical development, and also in some cases, the marketing, of synthetic or natural pharmaceuticals targeting this signalling system, which followed the understanding of the physiological and pathological role of endocannabinoids in several conditions, a role that was investigated first in rodent experimental models and then in humans. </p><p> Endocannabinoids: Molecular, Pharmacological, Behavioral and Clinical Features is a monograph that presents interesting manuscripts selected by the editor on the subject. Chapters in this book include original research or reviews which report the relevance of the endocannabinoid system by describing the results of experimental evidence about the neurobiological role of the endocannabinoid system. The main topics include, but are not limited to: </p><p> *The genetics of cannabinoid CB1 and CB2 receptors and their tissue distribution, their splicing variants and polymorphisms, and the possible implications of all this in determining different behaviours as well as various pathological conditions and the addiction to substances of abuse. </p><p> *Pharmacological approaches describing the potential use in the central nervous system disorders of endocannabinoid-based drugs, such as cannabinoid receptor agonists and antagonists, inhibitors of endocannabinoid inactivation processes, and even plant cannabinoids other than THC and with a molecular mechanism of action. </p><p> *The role of the endocannabinoid system in several neurological and neuropsychiatric conditions, such as epilepsy. </p><p> The volume would be a great interest to neuropharmacologists, physiologists and biochemists who aim to learn about the endocannabinoid system in detail.

Frontiers in Clinical Drug Research - Alzheimer Disorders is an e-Book series concerned with Alzheimer's disease (AD) that causes dementia, or loss of brain function. The disease affects the parts of the brain that deal with memory, thought, and language. Chapters in each volume focus on (Alzheimer Disorders) drug research with special emphasis on clinical trials, research on drugs in advanced stages of development and cure for Alzheimer’s disease and related disorders. </p><p> Frontiers in Clinical Drug Research - Alzheimer Disorders will be of particular interest to readers interested in drug therapy this specific neurodegenerative condition and related brain disorders as the series provides relevant reviews written by experts in field of Alzheimers Disease research.

Frontiers in Clinical Drug Research – Central Nervous System presents the latest research and clinical studies on the central nervous system (CNS). It covers a range of topics such as the development and pathophysiology of the brain and spinal cord, physiological sites of drug action in the CNS and clinical findings on drugs used to treat CNS defects due to injury or impaired development. In addition to clinical research on humans, the book also highlights other avenues of CNS medicine and research such as pain medicine, stem cell research, pharmacology, toxicology and translational models in animals. The first volume of the series features chapters on the following topics: -Nerve targets in pain medicine -Spinal cord injury -Research on neurotoxins targeting voltage gated ion channels -G protein coupled receptor agonists and modulators -Drug research on mediating hypoxia in developing white matter

- Frontiers in Clinical Drug Research - CNS and Neurological Disorders is an ebook series that brings updated reviews to readers interested in advances in the development of pharmaceutical agents for the treatment of central nervous system (CNS) and other nerve disorders. The scope of the ebook series covers a range of topics including the medicinal chemistry, pharmacology, molecular biology and biochemistry of contemporary molecular targets involved in neurological and CNS disorders. Reviews presented in the series are mainly focused on clinical and therapeutic aspects of novel drugs intended for these targets. Frontiers in Clinical Drug Research - CNS and Neurological Disorders is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critical information for developing clinical trials and devising research plans in the field of neurology. The second volume of this series features 8 chapters that cover a variety of topics including: -treatment of multiple sclerosis and schizophrenia -neurochemistry of tremors -relationship between GABA and Alzheimer&rsquo;s disease therapy -relationship between neurological diseases and cancer -research on angiogenesis-related blindness