BookPaolo Martelletti, Lars Edvinsson, editors.
Summary: Published in the series Headache, endorsed by the European Headache Federation, this is the first book on the novel synthetic treatment of migraine with ditans (lasmiditan) and gepants (atogepant, ubrogepant, rimegepant, vazegepant). These drugs will provide additional options for people with migraine put at risk of side effects by other medications or with unsatisfactory response to previous drugs. There is now a sufficient amount of literature published to interest a wide multidisciplinary readership (general physicians, general neurologists, clinical psychologists, neurologists in training, and medical students) facing every day this burdensome disorder in their clinical practice. The book aims therefore at offering an overview of these new drugs for both acute and prophylactic treatments of migraine, covering studies on clinical evidence, tolerability, and the different stages of clinical development.
Contents:
Intro
Foreword
Preface
Contents
Chapter 1: Novel Pharmacological Targets of Migraine: An Overview
1.1 Introduction
1.2 Novel Pharmacological Treatments for Migraine
1.3 Acute Treatment for Migraine Beyond Ergots and Triptans
1.3.1 5-HT1F Agonists: Ditans
1.3.2 CGRP Receptor Antagonists: Gepants
1.4 Gepants as Prophylactic Treatment for Migraine
1.5 Mechanisms of Action of Ditans and Gepants: Is It a Common Pathway?
1.6 Conclusion
References
Chapter 2: Molecular and Cellular Mechanisms of CGRP Antagonists
2.1 Introduction 2.1.1 Trigeminovascular System
2.2 Neuropeptide Signaling
2.2.1 CGRP
2.2.2 Amylin
2.2.3 Neuropeptide Receptors
2.2.4 Downstream Activation
2.3 The Blood-Brain Barrier
2.4 CGRP Antagonists
2.5 Molecular Targets
2.6 Cellular Targets
2.6.1 Vascular Targets
2.6.2 Trigeminal Targets
2.6.2.1 Satellite Glial Cells
2.6.2.2 Neuronal Targets
2.6.2.3 Potential Antagonistic Effect at the Nodes of Ranvier
2.7 Non-migraine Targets
2.8 Conclusion
References
Chapter 3: Atogepant
3.1 Introduction 3.2 Chemical Characteristics, Pharmacodynamics and Pharmacokinetics
3.3 Atogepant in Preclinical Studies
3.4 Efficacy of Atogepant in Phase II and Phase III Clinical Trials
3.5 Safety and Adverse Events
3.6 Future Developments
3.7 Conclusions
References
Chapter 4: Ubrogepant
4.1 Introduction
4.2 Pharmacology
4.2.1 Chemistry
4.2.2 Pharmacodynamics
4.2.3 Pharmacokinetics and Metabolism
4.3 Clinical Registered Trials
4.3.1 Phase I Trials
4.3.2 Phase II Trials
4.3.3 Phase III Trials: ACHIEVE I and II and Their Extension Study 4.3.4 Post-marketing Studies
4.4 Safety and Tolerability
4.5 Regulatory Affairs and Clinical Approval
4.6 Conclusions
References
Chapter 5: Rimegepant
5.1 Introduction
5.2 Introduction to the Compound
5.2.1 Chemistry
5.2.2 Pharmacodynamics
5.2.3 Pharmacokinetics and Metabolism
5.2.4 Metabolism
5.2.5 Drug Interactions
5.3 Clinical Efficacy
5.3.1 Phase II Studies
5.3.2 Phase III Studies
5.4 Safety and Tolerability
5.4.1 Phase I Studies
5.4.2 Phase II Studies
5.4.3 Phase III Studies
5.5 Exclusion Criteria
5.6 Conclusions
References Chapter 6: Zavegepant
6.1 Introduction
6.2 Preclinical Pharmacology
6.3 Clinical Trials
6.3.1 Safety and Tolerability
6.3.2 Efficacy
6.4 Conclusion
References
Chapter 7: Molecular Mechanisms of 5-HT1F Receptor Agonists
7.1 Serotonin (5-HT) and 5-HT Receptors
7.2 5-HT1B/D and 5-HT1F Receptors and Migraine Treatment
References
Chapter 8: Lasmiditan
8.1 Introduction
8.2 Pharmacological Profile
8.3 Preclinical Studies
8.4 Clinical Studies
8.5 Safety
8.6 Drug Interactions
8.7 Conclusion
References