Principles of CNS drug development -- Contents -- Acknowledgements -- Preface -- Abbreviations -- 1 Introduction -- 1.1 The global burden of CNS disease -- 1.2 Assessment of the global burden of disease -- 1.3 The prevalence of CNS disorders -- 1.4 Disability due to CNS disorders -- 1.5 Economic Costs -- 1.6 Concluding comments -- References -- 2 An overview of the major CNS disorders -- 2.1 Introduction -- 2.2 Overview of psychiatric disorders -- 2.3 Overview of neurological/neurodegenerative disorders -- 2.4 Concluding comments -- References -- 3 Neurobiological substrates of CNS disorders -- 3.1 Introduction -- 3.2 Brief introduction to the principles of chemical neurotransmission -- 3.3 Stages of chemical neurotransmission -- 3.4 Approaches to investigating CNS alterations in CNS disorders -- 3.5 Evidence for a neurobiological rationale for CNS disorders -- 3.6 Concluding comments -- References -- 4 Current pharmacological targets -- 4.1 Introduction -- 4.2 Pharmacological treatments for depression -- 4.3 Pharmacological treatments for schizophrenia -- 4.4 Pharmacological treatments for anxiety disorders -- 4.5 Pharmacological treatments for epilepsy -- 4.6 Pharmacological treatments for Parkinson's disease -- 4.7 Pharmacological treatments for Alzheimer's disease -- 4.8 Concluding comments -- References -- 5 Premarketing efficacy evaluation -- 5.1 Introduction -- 5.2 Target identification -- 5.3 Lead optimisation -- 5.4 Target validation in animal models -- 5.5 The use of genetically modified animals in CNS drug development -- 5.6 A selection of animal models of psychiatric disease -- 5.7 A selection of animal models of neurodegenerative disease -- 5.8 Which models to choose -- 5.9 Clinical trials that evaluate drug efficacy -- 5.10 Specific drug profiles -- References.

6 Pharmacokinetic considerations: Absorption, distribution, metabolism and elimination -- 6.1 Introduction -- 6.2 What are the 'ideal' pharmacokinetic properties for a CNS drug? -- 6.3 Absorption -- 6.4 Distribution -- 6.5 Metabolism -- 6.6 Elimination -- 6.7 Measurement of drug concentrations -- 6.8 Factors that affect pharmacokinetics -- 6.9 Allometric scaling -- 6.10 Microdosing (Phase 0) Studies -- 6.11 Dose prediction and therapeutic drug monitoring -- 6.12 Stereoselectivity of metabolism of drugs -- 6.13 Specific drug profiles -- 6.14 Concluding comments -- References -- 7 Safety concerns -- 7.1 Introduction -- 7.2 Postmarketing surveillance -- 7.3 Acute poisoning -- 7.4 Quantification of the relative risk of fatalities from CNS drugs -- 7.5 Adverse drug reactions (ADRs) -- 7.6 Specific types of toxicity encountered with psychotropic drugs -- 7.7 Safety concerns following long-term administration of CNS Drugs -- 7.8 Polypharmacy -- 7.9 Specific drug profiles -- 7.10 Concluding comments -- References -- Websites -- 8 Preclinical and clinical safety evaluation -- 8.1 Introduction -- 8.2 Preclinical exploratory toxicology and safety pharmacology evaluations -- 8.3 Primary and secondary pharmacology -- 8.4 Safety pharmacology -- 8.5 Toxicology studies required for regulatory purposes -- 8.6 Clinical Studies -- 8.7 Specific drug profiles -- 8.8 Concluding comments -- References -- Websites -- 9 CNS drug targets in development and future perspectives -- 9.1 Introduction -- 9.2 How much does it cost to develop a drug? -- 9.3 Clinical drug development times -- 9.4 Harmonisation between regulatory agencies -- 9.5 Development of biomarkers for clinical efficacy -- 9.6 Quality of life issues -- 9.7 Cost-effectiveness of novel treatments -- 9.8 Patient advocacy groups -- 9.9 Novel targets for CNS disorders -- 9.10 Targets in selected CNS disorders.

9.11 Targeting of signalling pathways -- 9.12 Cardiovascular drugs in Alzheimer's disease -- 9.13 Modifying oxidative stress and inflammatory responses -- 9.14 Targeting of the amyloid-β protein in Alzheimer's disease -- 9.15 Concluding comments -- References -- Appendices -- Index.