John Kelly

Principles of CNS Drug Development (eBook, PDF)

From Test Tube to Clinic and Beyond

• Format: PDF

Produktbeschreibung

This title acts as a primer, giving students and newcomers to the field an opportunity to learn about the breadth of the CNS drug discovery. The book outlines the core processes in drug discovery and development for CNS disorders, from evaluating drugs for desirable efficacy, safety and pharmacokinetic features in preclinical (using in vitro and in vivo models) and clinical experimentation to identifying future drug targets. Containing up-to-date experimental evidence and detailing the main impediments in the pipeline of CNS drug discovery and development, this is a key reference for those involved in all stages of CNS drug discovery. Key Features: * Discusses in detail the key stages of CNS drug discovery, outlining the particular requirements and obstacles for CNS drugs * Addresses safety concerns and future drug targets * Provides succinct background information about the major CNS diseases * Examples of specific drugs are used throughout to describe the development of a new drug from conception to clinical use and post-market surveillance * Primary reasons for drug failure are given for each stage

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Produktdetails

• Verlag: John Wiley & Sons
• Seitenzahl: 324
• Erscheinungstermin: 13. Oktober 2009
• Englisch
• ISBN-13: 9780470682913
• Artikelnr.: 37298874

Autorenporträt

Dr. John Kelly, Senior Lecturer, Department of Pharmacology and Therapeutics, NUI, Galway, Ireland.

Inhaltsangabe

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-ß protein in Alzheimer's disease. 9.15 Concluding comments.
References. Appendices. Index.