ISSN (Print): 1874-4672
ISSN (Online): 1874-4702
Volume 13, 4 Issues, 2020
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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702
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Author(s): Karoly Tihanyi and Monika Vastag
eISBN: 978-1-60805-120-5, 2011
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.
Author(s): Gary W. Caldwell
eISBN: 978-90-77527-12-2, 2007
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.
Editor(s): Eric Murillo-Rodríguez
Co-Editor(s): Emmanuel S. Onaivi, Nissar A. Darmani and Edward Wagner
eISBN: 978-1-60805-028-4, 2013
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.
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:
*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.
*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.
*The role of the endocannabinoid system in several neurological and neuropsychiatric conditions, such as epilepsy.
The volume would be a great interest to neuropharmacologists, physiologists and biochemists who aim to learn about the endocannabinoid system in detail.
Editor(s): John W. Cherwonogrodzky
eISBN: 978-1-60805-878-5, 2014
`Ricin Toxin’ brings together a collection of in depth and cutting edge reviews that focus on the current understanding of ricin toxins. This e-book provides a historical background, innovations in detection, identification and medical countermeasures against this biothreat, and the toxin’s previous use as an anti-cancer agent.
This e-book answers various important questions such as detection of ricin in food or soil, making of humanized antibody against the toxin, novel approaches for the creation of a safe vaccine to protect first responders, exploitation of toxin`s ability to bind and penetrate cells for medical benefits, aftereffects of administering antibody against ricin to a first responder and their exposure to the toxin, neutralization of different ricin from different castor plant cultivars. Aside from learning key concepts that may be overlooked while scanning literature, the reader will benefit from gems of information scattered throughout the book.
The book comprises of five different parts. The first part covers the background of ricin from pharaohs to bioterrorists and beyond.
The second part covers the discovery of recent technologies which are very helpful for the detection of ricin in different matrices, followed by the detection of ricin in the sorption of soils, minerals,textiles, and food; soil inflatration and dust transport. The third part covers the ricin and castor plant cultivars. It also discusses the antibody therapies such as Polyclonal and monoclonal antibodies and the extraction of ricin toxin from several cultivars of the Castor Plant (Ricinus communis).
The fourth part of this e-book discusses different medical countermeasures which are very effective in enhancing the progress in the development of vaccines against ricin intoxication. This part also describes different methods employed for the improvement of anti-ricin antibodies.
The last part of this book describes the replacement and different applications of the toxin. All chapters are written by paramount experts in ricin research.
`Ricin Toxin’ is an essential reading to all medical students, biochemists and professionals involved in the field of toxicology.