Keywords:
Drug development.
;
Psychotropic drugs-Development-Congresses.
;
Electronic books.
Type of Medium:
Online Resource
Pages:
1 online resource (457 pages)
Edition:
1st ed.
ISBN:
9783031210549
Series Statement:
Advances in Neurobiology Series ; v.30
URL:
https://ebookcentral.proquest.com/lib/geomar/detail.action?docID=7216748
DDC:
615.788
Language:
English
Note:
Intro -- Contents -- About the Editors -- Chapter 1: Drug Development in Psychiatry: The Long and Winding Road from Chance Discovery to Rational Development -- 1.1 Current Status of Psychiatric Diagnosis as a Rate-Limiting Step in Rational Psychiatric Drug Development -- 1.2 What Possible Changes Lie Ahead for Psychiatric Diagnoses? -- 1.3 The History of Current Psychiatric Drug Development: Chance Discovery and Rationale Refinement -- 1.4 The Future or Where to Go from Here? -- 1.5 The Immediate Future Which is Upbeat -- References -- Chapter 2: The History of Drug Development in Psychiatry: A Lesson in Serendipity -- 2.1 Introduction -- 2.2 Chlorpromazine -- 2.3 Monoamine Oxidase Inhibitors -- 2.4 Tricyclic Antidepressants -- 2.5 "Me Too" Drugs -- 2.6 Lithium -- 2.7 Valproate and Carbamazepine -- 2.8 Meprobamate and Mephenesin -- 2.9 LSD -- 2.10 Conclusion and Future Directions -- References -- Chapter 3: The Evolving Role of Animal Models in the Discovery and Development of Novel Treatments for Psychiatric Disorders -- 3.1 Introduction -- 3.2 Animal Models for Psychiatric Drug Discovery -- 3.2.1 Historical and Current Use of Animal Models for Psychiatric Disorders -- 3.2.2 Assessing the Validity of Animal Models -- 3.2.3 Types of Animal Models of Psychiatric Disorders -- Major Depressive Disorder -- Generalized Anxiety Disorder -- Post-Traumatic Stress Disorder -- Schizophrenia Spectrum and Other Psychotic Disorders -- Substance-Related and Addictive Disorders -- Attention Deficit Hyperactivity Disorder -- 3.2.4 Other Clinical Considerations to Modeling Psychiatric Disorders in Animals: Sex, Age, Ethnicity -- Sex and Age Differences in Symptomatology of Psychiatric Illnesses -- Sex and Age Differences in Response to Psychiatric Drugs -- Sex, Age, and Ethnicity Differences in Pharmacokinetics of Psychiatric Drugs.
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Use of Female Animals for Drug Discovery in Psychiatric Disorders -- 3.3 Utility of Animal Models Throughout the Stages of Modern Drug Discovery Stages -- 3.3.1 Target Identification and Validation -- 3.3.2 High-Throughput Screening/Hit-to-Lead -- 3.3.3 Early-, Mid-, and Late-Lead Optimization -- 3.3.4 Preclinical Candidate Selection -- 3.3.5 Translational Animal Models for Target Occupancy and Functional Target Engagement for Psychiatric Drug Discovery -- Imaging -- fMRI -- PET -- Quantitative EEG and Event-Related Potential Measurements -- 3.3.6 Example of In Vivo Target Validation of the Selective M4 PAM Mechanism for the Treatment of Schizophrenia -- 3.3.7 Example of In Vivo Characterization of the Selective mGlu5 NAM Basimglurant Through the Late Stage Preclinical Discovery -- 3.4 Future Innovations for Animal Models in Psychiatric Drug Discovery -- 3.4.1 RDoC Framework for Clinical to Preclinical Translational Studies for New Animal Model Development -- 3.4.2 Novel Technologies Enabling Development of Animal Models -- Novel Genetic Approaches -- Novel Techniques to Study Neurocircuitry Abnormalities in Psychiatric Disorders -- Optogenetics and dLight Signaling Strategies -- DREADDs -- GCaMP -- Novel High-Throughput Behavioral Screening Technologies -- 3.5 Summary and Future of Animal Models in Psychiatric Drug Discovery -- References -- Chapter 4: Discovery and Development of Monoamine Transporter Ligands -- 4.1 Introduction and Overview of Monoamine Transporters -- 4.2 Therapeutic Relevance of MATs -- 4.3 Structural Insights and Transport Mechanism -- 4.4 Central Binding Site Versus Allosteric Binding Sites in MATs -- 4.5 Medicinal Chemistry of MAT Ligands -- 4.5.1 Structure-Activity Relationship Studies of DAT Ligands -- 4.5.2 Structure-Activity Relationship Studies of SERT Ligands.
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4.5.3 Structure-Activity Relationship Studies of NET Ligands -- 4.6 Conclusion -- References -- Chapter 5: Drug Development for New Psychiatric Drug Therapies -- 5.1 The Drug Development Pathway -- 5.1.1 Pathway Overview -- 5.1.2 Drug Development Costs -- 5.1.3 Regulatory Overview -- 5.1.4 Types of Drug Therapies -- New Molecular Entities -- Generics -- 5.2 Preclinical Drug Development Phase -- 5.2.1 Characterization -- 5.2.2 Developing a Formulation Prototype -- 5.2.3 In Vitro-in Vivo Testing -- 5.2.4 Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis -- Animal Models -- 5.2.5 Mutagenicity -- 5.2.6 Toxicology Considerations -- 5.2.7 Regulatory Pathway: Preclinical to Clinical Trials -- 5.2.8 Investigational New Drug (IND) Application -- 5.3 Clinical Development Phase -- 5.3.1 Phase I Clinical Trials -- 5.3.2 Phase II Clinical Trials -- 5.3.3 Phase III Clinical Trials -- 5.3.4 Pediatric Considerations -- 5.4 Regulatory Review Process -- 5.4.1 Regulatory Pathway: Clinical Trials to Commercialization -- 5.4.2 NDA Review and Approval -- 5.4.3 Abbreviated NDAs -- 5.4.4 Advisory Committees -- 5.4.5 Expedited Review Programs -- 5.4.6 Prescription Drug Labeling Information -- 5.5 Phase IV Activities -- 5.5.1 Phase IV Clinical Trials -- 5.5.2 Monitoring Adverse Effects -- 5.5.3 Phase IV Health Outcomes/Quality of Life -- 5.6 Bioethical Issues -- 5.7 Conclusions -- References -- Chapter 6: Post-Approval Research in Drug Development: Priorities and Practices -- 6.1 Priorities -- 6.2 Regulatory Commitments -- 6.3 Further Clinical Considerations -- 6.4 Payer Considerations -- 6.5 Decisions: What Gets Studied? -- 6.6 Practices -- 6.7 Conclusions -- References -- Chapter 7: Discovery of New Transmitter Systems and Hence New Drug Targets -- 7.1 Introduction -- 7.1.1 Limitations in Psychiatric Drug Development -- 7.1.2 Neurotransmitter Systems.
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7.1.3 Genetic Basis for Drug Discovery -- 7.1.4 Timeline from Discovery to Approval -- 7.2 Orexin Pathway -- 7.2.1 Orexin Neurotransmitters and Receptors -- 7.2.2 Mechanism of Action -- 7.2.3 Role of Orexin in CNS Diseases -- 7.3 History of Dual Orexin Receptor Antagonists -- 7.3.1 Almorexant -- 7.3.2 SB-649868 -- 7.3.3 Lemborexant -- 7.3.4 Filorexant -- 7.4 Suvorexant -- 7.4.1 Mechanism of Action -- 7.4.2 Clinical Trial Results -- 7.5 Targeted Drug Development -- 7.6 Conclusions -- References -- Chapter 8: Reverse Engineering Drugs: Lorcaserin as an Example -- 8.1 Introduction -- 8.2 Overview of CNS Disorders and Drug Development -- 8.3 Approaches to Drug Development -- 8.4 Reverse Engineering -- 8.5 History of Seratonin Receptors -- 8.6 5HT2 Receptor Agonists -- 8.7 Lorcaserin -- 8.8 Reverse Engineering in Drug Discovery -- 8.9 Conclusions -- References -- Chapter 9: Back to the Future of Neuropsychopharmacology -- 9.1 Breakthrough Discoveries in the Past: What Made Them Possible? -- 9.2 The Schizophrenic Mouse 1.0: How It Was Done in the Past -- 9.3 The Schizophrenic Mouse 2.0: Reverse Engineering Approaches -- 9.4 Redefining the Use of Animal Models in Neuropsychiatric Drug Discovery -- 9.4.1 Lesson 1: Do Not Expect a Mouse with Schizophrenia -- 9.4.2 Lesson 2: Understand Drug-Target Interactions -- 9.4.3 Lesson 3: Be Confident in the Data -- 9.4.4 Lesson 4: Adopt Transparent and Open Science Practices -- References -- Chapter 10: Targeted Treatments for Fragile X Syndrome -- 10.1 Introduction: Overview of Fragile X Spectrum Disorders Including the Full Mutation and FXS and Premutation Disorders -- 10.2 Animal Models Guiding Targeted Treatments -- 10.2.1 KO Mouse Model and Drosophila Model for FXS -- 10.2.2 Downside of Animal Models -- 10.3 FMRP Deficits and Pathways that Are Dysregulated in the Absence of FMRP.
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10.4 Symptomatic Treatments for FXS -- 10.4.1 Stimulants and Alpha Agonists -- 10.4.2 Antidepressants -- 10.4.3 Antipsychotics -- 10.4.4 Mood Stabilizers -- 10.5 mGluR5: The Failed Translation of Preclinical Success -- 10.5.1 Target Supported by Theory -- 10.5.2 mGluR5 Human Trials -- 10.6 Targeted Treatments Not Yet FDA Approved -- 10.7 Targeted Treatments Available Currently -- 10.7.1 Minocycline -- 10.7.2 Metformin -- 10.7.3 Cannabidiol (CBD) -- 10.8 Lessons Learned -- 10.8.1 Easier to Cure the Mouse than the Human -- 10.8.2 How to Avoid a Placebo Effect -- 10.8.3 Quantitative Outcome Measures Are a Necessity -- 10.8.4 Measuring Cognition with the NIH Toolbox -- 10.8.5 New Language Outcome Measures -- 10.8.6 Multimodality Treatment Can Be Synergistic -- 10.8.7 Earlier Treatments Can Build a Better Brain -- 10.9 Summary -- 10.10 Definitions/Assessments -- References -- Chapter 11: The Difficult Path to the Discovery of Novel Treatments in Psychiatric Disorders -- 11.1 Is There a Problem with the Discovery of New Therapeutics for Psychiatric Disorders? -- 11.1.1 Why Are Most Drugs for Psychiatric Disorders Similar? -- 11.2 Drug Discovery -- 11.2.1 Defining Drugs and the Limitations of Therapeutic Benefit -- 11.2.2 The Process of Drug Discovery -- 11.2.3 The Economics of Drug Discovery and Development -- 11.3 The Unique Problems of CNS Drug Discovery in General and Psychiatric Drug Discovery in Particular -- 11.3.1 Why Is CNS Drug Discovery Difficult? -- 11.3.2 The Complicated Landscape of Psychiatric Drug Discovery -- 11.3.3 Schizophrenia Spectrum as a Disorder and a Drug Target -- 11.4 How Can We Move Psychiatric Drug Discovery Forward? -- 11.4.1 Biomarkers in Psychiatry -- 11.5 New Approaches in Drug Discovery for Schizophrenia -- 11.6 Conclusions -- References.
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Chapter 12: Biomarkers in Psychiatric Drug Development: From Precision Medicine to Novel Therapeutics.
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