This one-stop reference is the first to present the complete picture -- covering all relevant organisms, from single cells to mammals, as well as all major disease areas, including neurological disorders, cancer and infectious diseases.Addressing the needs of the pharmaceutical industry, this unique handbook adopts a broad perspective on the use of animals in the early part of the drug development process, including regulatory rules and limitations, as well as numerous examples from real-life drug development projects. After a general introduction to the topic, the expert contributors from research-driven pharmaceutical companies discuss the basic considerations of using animal models, including ethical issues. The main part of the book systematically surveys the most important disease areas for current drug development, from cardiovascular to endocrine disorders, and from infectious to neurological diseases. For each area, the availability of animal models for target validation, hit finding and lead profiling is reviewed, backed by numerous examples of both successes and failures among the use of animal models. The whole is rounded off with a discussion of perspectives and challenges.Key knowledge for drug researchers in industry as well as academia.

PrefacePART I: Transversal Issues Concerning Animal Models in Drug DiscoveryTHE 3Ns OF PRECLINICAL ANIMAL MODELS IN BIOMEDICAL RESEARCHFirst N: The Need for Use of Animal ModelsSecond N: The Need for Better Animal ModelsThird N: The Need for 3Rs Guiding PrinciplesALTERNATIVE MODELS IN DRUG DISCOVERY AND DEVELOPMENT PART I: IN SILICO AND IN VITRO MODELSIntroductionIn Silico ModelsIn Vitro ModelsALTERNATIVE MODELS IN DRUG DISCOVERY AND DEVELOPMENT PART II: IN VIVO NONMAMMALIAN AND EXPLORATORY/EXPERIMENTAL HUMAN MODELSIntroductionIn Vivo Nonmammalian ModelsIn Vivo Exploratory and Experimental Human ModelsETHICAL ISSUES AND REGULATIONS AND GUIDELINES CONCERNING ANIMAL RESEARCHIntroductionCurrent Use of Animals in Biomedical and Pharmaceutical ResearchEhtical Concerns and Positions on Animal ResearchGeneral Principles for the Ethical Use of Animals in ResearchRegulatory Framework for Use of Animals in ResearchREGULATORY ISSUES: SAFETY AND TOXICOLOGY ASSESSMENTIntroductionAnimal Species in Toxicology StudiesToxicology StudiesTranslation to Clinics: Limitations and DifficultiesGENERATION AND USE OF TRANSGENIC MICE IN DRUG DISCOVERYIntroductionImproved Mouse Genetic EngineeringFunctional Evaluation and Uses of Mouse ModelsTranslation to Clinics: Limitations and DifficultiesPerspectivesIN VIVO BRAIN IMAGING IN ANIMAL MODELS: A FOCUS ON PET AND MRIIntroduction: Role of Animal in In Vivo ImagingThe Choice of the Right Imaging Modality for Brain ImagingSmall Animal Magnetic Resonance ImagingPositron Emission TomographyClinical Translation: Limitations and DifficultiesPART II: Animal Models in Specific Disease Areas of Drug DiscoverySUBSTANCE ABUSE AND DEPENDENCEIntroductionDifficulties to Model Addiction in AnimalsTolerance, Sensitization, and Physical WithdrawalReward and ReinforcementTranslation to Clinics: Limitations and DifficultiesMOOD AND ANXIETY DISORDERSIntroductionAnimal Models of Anxiety DisordersAnimal Models of Mood DisordersTranslation to Clinics: Limitations and DifficultiesSCHIZOPHRENIAIntroductionModels Amenable to Use in ScreeningTranslation to Clinics: Limitations and DifficultiesMIGRAINE AND OTHER HEADACHESIntroductionVascular ModelsNeurogenic InflammationNociceptive Activation of the Trigeminovascular SystemCortical Spreading DepressionHuman Experimental Migraine Provoking ModelsAnimal Experimental Migraine Provoking ModelsTransgenic ModelsBehavioral ModelsTranslation to Clinics: Limitations and DifficultiesNOCICEPTIVE, VISCERAL, AND CANCER PAINIntroductionAcute Pain TestsVisceral Pain ModelsCancer Pain ModelsTranslation to Clinics: Limitations and DifficultiesINFLAMMATORY, MUSCULOSKELETAL/JOINT (OA AND RA), AND POSTOPERATIVE PAINIntroduction: Evaluation of Pain in Animal ModelsInflammatory PainMusculoskeletal/Joint Osteoarthritis (OA) and Rheumatoid Arthritis (RA) PainPostoperative PainTranslation to Clinics: Limitations and DifficultiesNEUROPATHIC PAINIntroductionMain Types of Neuropathic Pain in HumansModelization of Chronic Pain in RodentsTranslation to Clinics: Limitations and DifficultiesOBESITY AND METABOLIC SYNDROMEIntroductionWhy Metabolic Syndrome?Classical Animal Models of Obesity and Metabolic SyndromeHuman Experimental ModelsTranslation to Clinics: Limitations and DifficultiesCOGNITIVE DISORDERS: IMPAIRMENT, AGING, AND DEMENTIAIntroductionPharmacological ModelsAging and Transgenic ModelsTranslation to Clinics: Limitations and DifficultiesSTROKE AND TRAUMATIC BRAIN INJURYIntroductionStroke ModelsTraumatic Brain Injury ModelsTranslation to Clinics: Limitations and DifficultiesMOVEMENT DISORDERS: PARKINSON'S DISEASEIntroductionDrug- and Toxin-Based Models of PDGenetic and Functional Models of PDTranslation to Clinics: Limitations and DifficultiesEPILEPSY: ANIMAL MODELS TO REPRODUCE HUMAN ETIOPATHOLOGYIntroductionWhat Animal Species to Use to Model Epilepsy?Which Type of Models Provide