Living systems exhibit a fundamental contradiction: they are highly stable and reliable, yet they have the capacity to adapt to changing environmental conditions. This paradoxical behavior arises from the complexity of life--a high degree of order and cooperation that emerges from relatively simple interactions among cellular components. The Complexity Paradox proposes inventive, interdisciplinary approaches to maintaining health and managing and preventing disease by considering the totality of human biology, from the cellular level on up to entire populations of individuals. From the perspective of complexity, which acknowledges that there are limits to what we can know, Kenneth L. Mossman opens the door to understanding essential life processes in new and extraordinary ways. By tying together evolution, functional dynamics, and investigations into how the body processes energy and uses genetic information, Mossman's analysis expresses a unified theory of biology that fills a critical niche for future research in biology, medicine, and public health.

Computational methods, and in particular quantum chemistry, have taken the lead in our growing understanding of noncovalent forces, as well as in their categorization. This volume describes the current state of the art in terms of what we now know, and the current questions requiring answers in the future. Topics range from very strong (ionic) to very weak (CH-- ) interactions. In the intermediate regime, forces to be considered are H-bonds, particularly CH--O and OH--metal, halogen, chalcogen, pnicogen and tetrel bonds, aromatic stacking, dihydrogen bonds, and those involving radicals. Applications include drug development and predictions of crystal structure.

If you had the chance to heal and live a journey of unimaginable proportions, would you? an odyssey, not unlike Homer's Odyssey in its journey into the fantastical, or the Iliad, which deals with the truth of war in its tragedy and scope. NDMA. A corporate by-product which launches a journey of epic and fantastical proportions, the poison of the NDMA creating a sensory psychic and empath with untold knowledge, a woman who had to become secluded from the world because of her ability to feel atomic energy in the form of people's diseases and the world's pain. never before lived that brings a new understanding that will change the perceptions of 8 billion people with regard to politics, economics, medicine, religion, the environment, law and war. would change the face of life on this planet, would you?

Toxins are important virulence determinants responsible for microbial pathogenicity and/or evasion of the host immune response. Understanding the molecular and cellular biology of toxins is critical for the development of new anti-toxin strategies, particularly for those with bioterrorism capability. Indeed, potential applications of toxin research extend beyond simply combating microbial virulence and include the development of novel anti-cancer drugs and other frontline medicines, use of toxins as tools in neurobiology and cellular biology, etc. This timely volume serves as an update on important recent advances. Written by internationally respected scientists, topics reviewed include: toxins carried by mobile genetic elements, botulinum neurotoxins, anthrax, subtilase cytotoxin, Pasteurella multocida toxin, RTX toxins of vibrios, vacA toxin, staphylococcal immune evasion toxins, and fungal ribotoxins. The book is essential reading for everyone with an interest in microbial toxins, and it is recommended for other scientists with an interest in microbiology, bioterrorism, microbial pathogenesis, and microbial genomics.

Theintentionofthisbookistoprovideacomprehensiveandcontemporaryreview ofthebiologyofsensorynerves. InkeepingwiththethemeoftheHandbookof Experimental Pharmacology series, emphasis will be placed on the actions of drugs,transmittersandautacoidsthatinitiateorinhibitsensorynerveactivation (through actionsonionchannelsandreceptorsattheirperipheralterminals)or modulate the release or actions of the transmitters released from the central terminalsofsensorynerves. Onthebasisofextensivesupportiveevidenceinthe literature, it is our view that many diseases are characterized by alterations in sensorynervefunction(e. g. pain,cardiovasculardiseaseandmigraine). Itisour beliefthatthisbookwillbeunique,asitwillcomprehensivelycovertheroleof sensory nerves across many therapeutic areas. To address directly one of the editorialboardqueries,thisisnotintendedtobeabookaboutthepharmacology ofpain. Thatsaid,tomostpharmacologists,painisthemostobviousindicationfor aroleorsensorynervesindisease. Webelievethatthelessonslearntfromthestudy ofneuropathicpainwillbeinvaluableforresearchersintheothertherapeuticareas covered inthisvolume. Sincemostinterest hasfocusedontheroleofsensory nervesinneuropathicpain,wehaveaddedanumberofchaptersdevotedtothis subject. Thebookisorganizedinthreeparts,coveringthetypesandrolesofsensory nervesinsomaticandvisceraldisorders(PartI),speci?ctargetsonsensorynerves relevanttopainandvisceraldisorders(PartII)andadescriptionofcurrentand futuretherapeuticstrategiesfortargetingsensorynerves(PartIII). The?rsttwochaptersinPartIaredevotedtodescribingtheclinicalfeaturesof neuropathicpainandvisceralpain. Ourintentionisfortheauthorstoprovidea clinicalviewpointonthefeaturesoftheseconditionsandtheadvantages/disadv- tagesofcurrenttreatmentmodalities. Thenext?vechaptersinPartIfocusonthe roleofsensorynervesinotherpathologicalconditions. Severalcommonthemes willemergeinthispart,includingthemodeofsensorynerveactivationinvarious tissues and organs, the alterations in sensory nerve excitability associated with disease,andtheimportanceofin?ammationandin?ammatorymediatorsininiti- ingalteredsensorynervefunctionindisease. v vi Preface Whilstthe?rstpartfocusesontheclinicaland/orsystemsphysiology,PartIIhas itsfocusatthecellandmolecularlevel. Thisparthighlightsthecurrentundersta- ingofproteins/ionchannels/mediatorsthathavecreatedthemostintenserecent interestintheareaofsensorynervebiology. Together,thesechapterswillgivethe reader important knowledge about how sensory nerve function can be altered pharmacologically. Thelastchapterinthispartdescribestheprocessesthatgive risetoalteredneuralre?exesatthecentrallevel. Themechanismsdescribedin thesechaptersreinforcetheroleofproteins/mediatorshighlightedinthepreceding chapters. Theroleofthesecellular,molecularandphysiologicalprocessesinthe diseasesdiscussedinPart1areemphasized. TheaimofPartIIIistohighlightpotentialdrugtargetsthatmightaltersensory nervefunction. Mostoftheworkhasbeendevotedtothetreatmentofneuropathic painandsothispartheavilyemphasizesthissubject. However,aswillbeapparent fromPartI,manyofthesetargetscouldbeutilizedinothertherapeuticareasthat implicatesensorynervesintheirpathophysiologicalprocesses. Thefocusofthe chaptersisonopioidsandmodulatorsofionchannelsandthenthe?nalchapteris devotedtofuturetreatmentstrategiesforneuropathicpain. Finally,wewouldliketothankallthecontributors,includingco-authors,who agreedtowritechaptersforthisbookandthepublishers,especiallySusanneDathe, fortheirpatienceandassistance. Baltimore B. J. Canning London D. Spina Contents PartI RoleofSensoryNervesinDisease NeuropathicPain:AClinicalPerspective ...3 RalfBaron VisceralPain:TheNeurophysiologicalMechanism...31 JyotiN. Sengupta Migraine ...75 SilviaBenemei,PaolaNicoletti,JayG. Capone,Francesco DeCesaris,andPierangeloGeppetti AfferentNerveRegulationofBladderFunctioninHealth andDisease ...91 WilliamC. deGroatandNaokiYoshimura SensoryNervesandAirwayIrritability...139 B. J. CanningandD. Spina RegulationofCardiacAfferentExcitabilityinIschemia...185 Liang-WuFuandJohnC. Longhurst RolesofGastro-oesophagealAfferentsintheMechanisms andSymptomsofRe?uxDisease ...227 AmandaJ. PageandL. AshleyBlackshaw PartII CellandMolecularMechanismsRegulatingSensory NerveFunction TransientReceptorPotentialChannelsonSensoryNerves ...261 S. R. EidandD. N. Cortright Acid-SensitiveIonChannelsandReceptors ...283 PeterHolzer PurinesandSensoryNerves...333 GeoffreyBurnstock vii viii Contents Sensory-Nerve-DerivedNeuropeptides: PossibleTherapeuticTargets ...393 ElizabethS. Fernandes,SabineM. SchmidhuberandSusanD. Brain CytokineandChemokineRegulationofSensory NeuronFunction ...417 RichardJ. Miller,HosungJung,SoniaK. BhangooandFletcherA. White TheRoleofPeptidesinCentralSensitization ...451 V. S. Seybold PartIII CurrentandFutureTreatmentStrategiesTargeting SensoryNerves OpioidsandSensoryNerves ...495 ChristophSteinandChristianZoTheintentionofthisbookistoprovideacomprehensiveandcontemporaryreview ofthebiologyofsensorynerves. InkeepingwiththethemeoftheHandbookof Experimental Pharmacology series, emphasis will be placed on the actions of drugs,transmittersandautacoidsthatinitiateorinhibitsensorynerveactivation (through actionsonionchannelsandreceptorsattheirperipheralterminals)or modulate the release or actions of the transmitters released from the central terminalsofsensorynerves. Onthebasisofextensivesupportiveevidenceinthe literature, it is our view that many diseases are characterized by alterations in sensorynervefunction(e. g. pain,cardiovasculardiseaseandmigraine). Itisour beliefthatthisbookwillbeunique,asitwillcomprehensivelycovertheroleof sensory nerves across many therapeutic areas. To address directly one of the editorialboardqueries,thisisnotintendedtobeabookaboutthepharmacology ofpain. Thatsaid,tomostpharmacologists,painisthemostobviousindicationfor aroleorsensorynervesindisease. Webelievethatthelessonslearntfromthestudy ofneuropathicpainwillbeinvaluableforresearchersintheothertherapeuticareas covered inthisvolume. Sincemostinterest hasfocusedontheroleofsensory nervesinneuropathicpain,wehaveaddedanumberofchaptersdevotedtothis subject. Thebookisorganizedinthreeparts,coveringthetypesandrolesofsensory nervesinsomaticandvisceraldisorders(PartI),speci?ctargetsonsensorynerves relevanttopainandvisceraldisorders(PartII)andadescriptionofcurrentand futuretherapeuticstrategiesfortargetingsensorynerves(PartIII). The?rsttwochaptersinPartIaredevotedtodescribingtheclinicalfeaturesof neuropathicpainandvisceralpain. Ourintentionisfortheauthorstoprovidea clinicalviewpointonthefeaturesoftheseconditionsandtheadvantages/disadv- tagesofcurrenttreatmentmodalities. Thenext?vechaptersinPartIfocusonthe roleofsensorynervesinotherpathologicalconditions. Severalcommonthemes willemergeinthispart,includingthemodeofsensorynerveactivationinvarious tissues and organs, the alterations in sensory nerve excitability associated with disease,andtheimportanceofin?ammationandin?ammatorymediatorsininiti- ingalteredsensorynervefunctionindisease. v vi Preface Whilstthe?rstpartfocusesontheclinicaland/orsystemsphysiology,PartIIhas itsfocusatthecellandmolecularlevel. Thisparthighlightsthecurrentundersta- ingofproteins/ionchannels/mediatorsthathavecreatedthemostintenserecent interestintheareaofsensorynervebiology. Together,thesechapterswillgivethe reader important knowledge about how sensory nerve function can be altered pharmacologically. Thelastchapterinthispartdescribestheprocessesthatgive risetoalteredneuralre?exesatthecentrallevel. Themechanismsdescribedin thesechaptersreinforcetheroleofproteins/mediatorshighlightedinthepreceding chapters. Theroleofthesecellular,molecularandphysiologicalprocessesinthe diseasesdiscussedinPart1areemphasized. TheaimofPartIIIistohighlightpotentialdrugtargetsthatmightaltersensory nervefunction. Mostoftheworkhasbeendevotedtothetreatmentofneuropathic painandsothispartheavilyemphasizesthissubject. However,aswillbeapparent fromPartI,manyofthesetargetscouldbeutilizedinothertherapeuticareasthat implicatesensorynervesintheirpathophysiologicalprocesses. Thefocusofthe chaptersisonopioidsandmodulatorsofionchannelsandthenthe?nalchapteris devotedtofuturetreatmentstrategiesforneuropathicpain. Finally,wewouldliketothankallthecontributors,includingco-authors,who agreedtowritechaptersforthisbookandthepublishers,especiallySusanneDathe, fortheirpatienceandassistance. Baltimore B. J. Canning London D. Spina Contents PartI RoleofSensoryNervesinDisease NeuropathicPain:AClinicalPerspective ...3 RalfBaron VisceralPain:TheNeurophysiologicalMechanism...31 JyotiN. Sengupta Migraine ...75 SilviaBenemei,PaolaNicoletti,JayG. Capone,Francesco DeCesaris,andPierangeloGeppetti AfferentNerveRegulationofBladderFunctioninHealth andDisease ...91 WilliamC. deGroatandNaokiYoshimura SensoryNervesandAirwayIrritability...139 B. J. CanningandD. Spina RegulationofCardiacAfferentExcitabilityinIschemia...185 Liang-WuFuandJohnC. Longhurst RolesofGastro-oesophagealAfferentsintheMechanisms andSymptomsofRe?uxDisease ...227 AmandaJ. PageandL. AshleyBlackshaw PartII CellandMolecularMechanismsRegulatingSensory NerveFunction TransientReceptorPotentialChannelsonSensoryNerves ...261 S. R. EidandD. N. Cortright Acid-SensitiveIonChannelsandReceptors ...283 PeterHolzer PurinesandSensoryNerves...333 GeoffreyBurnstock vii viii Contents Sensory-Nerve-DerivedNeuropeptides: PossibleTherapeuticTargets ...393 ElizabethS. Fernandes,SabineM. SchmidhuberandSusanD. Brain CytokineandChemokineRegulationofSensory NeuronFunction ...417 RichardJ. Miller,HosungJung,SoniaK. BhangooandFletcherA. White TheRoleofPeptidesinCentralSensitization ...451 V. S. Seybold PartIII CurrentandFutureTreatmentStrategiesTargeting SensoryNerves OpioidsandSensoryNerves ...495 ChristophSteinandChristianZollner ThePharmacologyofVoltage-GatedSodiumChannels inSensoryNeurones ...519 ReginaldJ. DochertyandClareE. Farmer RoleofCalciuminRegulatingPrimarySensory NeuronalExcitability ...563 T. D. Gover,T. H. MoreiraandD. Weinreich FutureTreatmentStrategiesforNeuropathicPain...589 FabienMarchand,NicholasG. JonesandStephenB.

The suspension dosage form has long been used for poorly soluble active ingre- ents for various therapeutic indications. Development of stable suspensions over the shelf life of the drug product continues to be a challenge on many fronts. A good understanding of the fundamentals of disperse systems is essential in the development of a suitable pharmaceutical suspension. The development of a s- pension dosage form follows a very complicated path. The selection of the proper excipients (surfactants, viscosity imparting agents etc.) is important. The particle size distribution in the finished drug product dosage form is a critical parameter that significantly impacts the bioavailability and pharmacokinetics of the product. Appropriate analytical methodologies and instruments (chromatographs, visco- ters, particle size analyzers, etc.) must be utilized to properly characterize the s- pension formulation. The development process continues with a successful scale-up of the manufacturing process. Regulatory agencies around the world require cli- cal trials to establish the safety and efficacy of the drug product. All of this devel- ment work should culminate into a regulatory filing in accordance with the regulatory guidelines. Pharmaceutical Suspensions, From Formulation Development to Manufacturing, in its organization, follows the development approach used widely in the pharmaceutical industry. The primary focus of this book is on the classical disperse system - poorly soluble active pharmaceutical ingredients s- pended in a suitable vehicle.

"Reward Deficit Disorders" is written for researchers in both academia and the pharmaceutical industry who use animal models in research and development of drugs for reward deficit disorders such as alcohol dependence, nicotine dependence, heroin and cocaine addiction, obesity, and gambling and impulse control disorders. "Reward Deficit Disorders "has introductory chapters expressing the view of the role and relevance of animal models for drug discovery and development for the treatment of psychiatric disorders from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in each therapeutic area covered and discuss the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. "Reward Deficit Disorders" also has a section dedicated to the specifics of the regulatory aspects to abuse liability testing. The aim of this series of volumes on "Animal and Translational Models for CNS Drug Discovery" is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery.

This is the third volume in the three volume-set, "Animal and Translational Models for CNS Drug Discovery" 978-0-12-373861-5, which is also available for purchase individually.
Provides clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery processCritical evaluation of animal and translational models improving transition from drug discovery and clinical developmentEmphasizes what results mean to the overall drug discovery processExplores issues in clinical trial design and conductance in each therapeutic areaNeurological Disorders is available for purchase individually.

1. Application of Transgenic and Gene-Targeted Mice to Dissect Mechanisms of Lung Disease.- Emphysema.- 2. Models of Genetic Emphysema: The C57B1/6J Mice and their Mutants: Tight-Skin, Pallid and Beige Giuseppe Lungarella, Eleonora Cavarra and.- 3. ?1-Antitrypsin Deficiency.- 4. Recombinant SLPI: Emphysema and Asthma.- 5. Elastase Inhibitors in the Lung: Expression and Functional Relationships.- 6. Regulation of Neutrophil Proteinases.- 7. Control of Connective Tissue Genes.- Infection.- 8. Genetic Models of Bacterial Lung Infection.- 9. Genetics of Bacteria: Role in Pathogenesis of Infection of the Respiratory Tract.- 10. Polymerase Chain Reaction in the Diagnosis of Respiratory Tract Infections.- 11. Cystic Fibrosis.- 12. Respiratory Bacterial Infections in Patients with Cystic Fibrosis: Pathogenicity and Implications for Serine Proteinase Inhibitor Therapy.

This volume collects a variety of techniques and methodologies developed to facilitate research on integrin biology and to identify ideal targets and approaches for the treatment of multiple organ diseases, with a focus on cancer in particular. The chapters consecutively describe the tools for structural analysis, identification and detection of integrins as biomarkers, and include thorough laboratory and clinically-related methods on different strategies for generation, synthesis and evaluation of probes, carriers, peptides or small particles for integrin targeting, imaging, and drug delivery. As part of the Methods in Pharmacology and Toxicology series, this book contains the practical details that are invaluable in the laboratory. Authoritative and advantageous, Integrin Targeting Systems for Tumor Diagnosis and Therapy serves readers from a wide spectrum, including researchers and students seeking an overview of existing developments, as well as leading professionals aiming to become more familiar with integrin-related innovative technologies in cancer research.

This accessible, easy-to-read book provides readers with different perspectives on the subject of painkillers, examining their history, production, uses, and dangers. Many different drugs are effectively used as painkillers-substances that greatly improve the quality of life for those who suffer from temporary or recurring pain. This book presents an in-depth overview of opiates, opioids, and other painkilling substances such as non-steroidal anti-inflammatory drugs (NSAIDs) that have been in use from ancient times up to the contemporary era. It also addresses the risks of painkiller use, their misuse, and potential overdose concerns. The latest in the Story of a Drug series and written by a subject expert who has published widely on drug use and pharmacology, this book presents a brief review of the science of how different painkiller drugs work before covering these substances' respective effects and applications; the issues regarding the production, distribution, and regulation of painkiller drugs; and research findings on painkiller use, abuse patterns, addiction, and policy issues. The easy-to-understand text presents scientifically accurate information that enables readers to better understand the key role of painkillers in our 21st-century world. Documents the risks of painkiller use and explores the various issues centered around the production, distribution, and regulation of painkiller medications Examines painkillers from a variety of perspectives, including medical, historical, economic, and social Includes primary source documents such as guidelines, policy documents, and study findings on the topics covered that provide readers with more in-depth information and help students hone their critical thinking and analytical skills Examines the social dimensions of the use and abuse of painkiller drugs and considers the future of this particular type of drugs

Drug discovery originating in Africa has the potential to provide significantly improved treatment of endemic diseases such as malaria, tuberculosis and HIV/AIDS. This book critically reviews the current status of drug discovery research and development in Africa, for diseases that are a major threat to the health of people living in Africa. Compiled by leading African and international experts, this book presents the science and strategies of modern drug discovery. It explores how the use of natural products and traditional medicines can benefit from conventional drug discovery approaches, and proposes solutions to current technological, infrastructural, human resources, and economic challenges, which are presented when attempting to engage in full-scale drug discovery. Topics addressed are varied; from African medicinal plants to marine bioprospecting, pharmacogenetics and the use of nanotechnology. This book brings together for the first time a collection of strategies and techniques that need to be considered when developing drugs in an African setting. It is an unprecedented and truly international effort, highlighting the remarkable effort made so far in the area of drug discovery research by African scientists, and scientists from other parts of the world working on African health problems.

This book systematically covers immunoassays for food, presenting detailed approaches such as antigen design, food matrix pre-treatment and detection format optimization for 9 classes of food hazards and nutrition constituents. Offering ideas on how to improve the efficiency of recognized xenobiotics and food contents, this practical book also describes the discovery and utilization of novel immune agents like aptamer and molecular imprinted polymers in food analysis. It is intended for a broad range of areas, including biologists and food chemists, and is sure to become a key reference resource for students and professionals alike.

Written by experts in the field, this comprehensive resource offers valuable information on the practical uses of drugs in primary eye care. Discussions of the pharmacology of ocular drugs such as anti-infective agents, anti-glaucoma drugs, and anti-allergy drugs lead to more in-depth information on ocular drugs used to treat a variety of disorders, including diseases of the eyelids, corneal diseases, ocular infections, and glaucoma. The book also covers ocular toxicology, focusing on drug interactions, ocular effects of systemic drugs, and life-threatening systemic emergencies. A logical organization makes it easy to find essential information. Complete coverage of the basic fundamentals of pharmacology such as ocular drug delivery and ocular drug formulations. Comprehensive reviews of the pharmacology of specific classes of agents such as the cycloplegics, antiglaucoma drugs, anti-inflammatory drugs, ocular irrigating solutions, and contact lens care products. In-depth information on ocular drugs used in clinical practice, including chapters on drugs used to treat eyelid disorders, lacrimal diseases, conjunctiva diseases, corneal diseases, allergies, uveitis, postoperative cataract, retinal diseases, and glaucoma. Coverage of ocular toxicology, including drug interactions, ocular effects of systemic drugs, and life-threatening systemic emergencies. Completely revised and updated content that reflects the latest advances in pharmacology. Updated information on post-operative drugs, including LASIK follow up medications. Expanded coverage in the chapters on Anti-infective Drugs, Anti-allergy Drugs and Decongestants, and Lubricants and Other Preparations of Ocular Surface Disease that includes the latest advancements in antibiotics and medications used to treat allergies and dry eye. A dosage quick reference guide on the inside front cover for quick and easy access. Information on the use of herbal medications.

In this volume, the specific challenges and problems facing the evaluation of new oncology agents are explored with regards to pharmacokinetic, pharmacodynamic modeling and clinical pharmacology development strategies. This book delivers, with an emphasis on the oncology therapeutic area, the goals set in the first three volumes: namely - to provide clinical pharmacologists practical insights for the application of pharmacology, pharmacokinetics and pharmacodynamics for new drug development strategies. Pharmacokinetic-pharmacodynamic concepts for tyrosine kinases, the evaluation of cardiac repolarization prolongation through QTc interval effects, efficacy- and safety-response analyses to support new drug approvals, clinical and preclinical tumor growth modeling, and flat- vs weight-based dose selection are showcased from an oncology clinical pharmacologist's point-of-view. Oncology development strategies are surveyed for new FDA-approvals to identify patterns in expectations at time of first approval. The special considerations necessary to address combination drug development, metronomics, biosimilars and breakthrough therapies are also presented.

Fully updated to reflect the nutritional needs of the '80s, this new edition of the classic guide to herbal medicine, natural foods and home remedies underscores the fundamental principle that true healing consists of a return to natural habits of living.

A concise, accessible account of pharmacology, covering all the key concepts you need with no gaps. It can be used either as an introduction to a topic, or as a revision aid. Big Picture Section - you can relate detail to the subject as a whole High Return Facts - fills large gaps in your knowledge. Can be used as a revision tool. Reinforces the major points Cartoon-strip illustrations - you can visualise difficult concepts in a step-by-step format - information is chunked into 'student-friendly' sizes Double-page overviews - read topic summaries without cross-referencing to other pages - they're all laid out in one spread!

This thorough volume delves into antiepileptic drug discovery with a comprehensive collection of innovative approaches for the development of antiepileptic therapies, focusing on novel molecular targets for antiepileptic drugs, computer-aided approaches for the identification of new drug candidates, and therapeutic strategies to overcome refractory epilepsy. The last section illustrates the potential benefits that network pharmacology and rational drug repurposing could bring to the antiepileptic drug discovery community. Written for the Methods in Pharmacology and Toxicology series, chapters include the kind of detailed description and implementation advice to ensure results in the laboratory. Authoritative and practical, Antiepileptic Drug Discovery: Novel Approaches aims to provide medicinal chemists, pharmacologists, and other researchers with the tools need to further explore the study of pharmacoresistant epilepsy and the discovery of new antiepileptic drugs.

The development of innovative drugs is becoming more difficult while relying on empirical approaches. This inspired all major pharmaceutical companies to pursue alternative model-based paradigms. The key question is: How to find innovative compounds and, subsequently, appropriate dosage regimens?

Written from the industry perspective and based on many years of experience, this book offers:

- Concepts for creation of drug-disease models, introduced and supplemented with extensive MATLAB programs

- Guidance for exploration and modification of these programs to enhance the understanding of key principles

- Usage of differential equations to pharmacokinetic, pharmacodynamic and (patho-) physiologic problems thereby acknowledging their dynamic nature

- A range of topics from single exponential decay to adaptive dosing, from single subject exploration to clinical trial simulation, and from empirical to mechanistic disease modeling.

Students with an undergraduate mathematical background or equivalent education, interest in life sciences and skills in a high-level programming language such as MATLAB, are encouraged to engage in model-based pharmaceutical research and development.

Reports on the emergence and prevalence of resistant bacterial infections in hospitals and communities raise concerns that we may soon no longer be able to rely on antibiotics as a way to control infectious diseases. Effective medical care would require the constant introduction of novel antibiotics to keep up in the "arms race" with resistant pathogens. This book closely examines the latest developments in the field of antibacterial research and development. It starts with an overview of the growing prevalence of resistant Gram-positive and Gram- negative pathogens, including their various resistance mechanisms, prevalence, risk factors and therapeutic options. The focus then shifts to a comprehensive description of all major chemical classes with antibacterial properties, their chemistry, mode of action, and the generation of analogs; information that provides the basis for the design of improved molecules to defeat microbial infections and combat the emerging resistances. In closing, recently developed compounds already in clinical use, those in preclinical or first clinical studies, and a number of promising targets to be exploited in the discovery stage are discussed.

Muscarinic acetylcholine receptors have played a key role in the advancement of knowledge of pharmacology and neurotransmission since the inception of studies in these fields, and the effects of naturally occurring drugs acting on muscarinic receptors were known and exploited for both therapeutic and non-therapeutic purposes for hundreds of years before the existence of the receptors themselves was recognized. This volume presents a broad yet detailed review of current knowledge of muscarinic receptors that will be valuable both to long-time muscarinic investigators and to those new to the field. It describes the detailed insights that have been obtained on the structure, function, and cell biology of muscarinic receptors. This volume also describes physiological analyses of muscarinic receptors and their roles in regulating the function of the brain and of a variety of peripheral tissues. This volume shows how the study of muscarinic receptors continues to provide new and surprising insights not just to the cholinergic system but to the broad areas of neurobiology, cell biology, pharmacology, and therapeutics.

Although it is one of the most-widely studied viruses, many mysteries still remain about HIV. Covering the latest advances and challenges associated with clinical application of new antiviral drugs and vaccines, this revised edition is a companion to Murad: "HIV-1: Molecular Biology and Pathogenesis, 2E." Leading investigators in HIV research present a timely picture of the molecular mechanisms which guide HIV-1 expression and replication and provide the most current clinical strategies for combating this virus.
* The latest developments in HIV-vaccine research
* New concepts in the discovery and design of novel anti-HIV drugs

This book covers research studies of aloe by the CAP (Creation Aloe Pharmaceuticals) team. It details the various physiological effects of those components for possible use as health foods or drugs. The team was organized into the isolation and analysis group, which purified many components in terms of low molecular weight compounds, carbohydrates, proteins present in aloe, and the assay group, which determined the efficacy of those components.