Abstract
Background: Migraine is a highly prevalent neurovascular disorder.
Objective: Of the many factors that have been implicated over the years, 5-hydroxytryptamine (5-HT; serotonin) has long been involved in the pathophysiology of migraine. Certainly, some lines of evidence suggest: (i) a 5-HT depletion from blood platelets resulting in cranial extracerebral vasodilatation; and (ii) the effectiveness of an intravenous (i.v.) infusion of 5-HT to abort migraine in some patients. More direct evidence comes from some drugs that influence 5-HT release and/or interact (as agonists or antagonists) with 5-HT receptors to treat this disorder. Indeed, the development of sumatriptan and second generation triptans in the 1990’s led to discover that these drugs produce selective cranial extracerebral vasoconstriction (via 5-HT1B receptors) and inhibition of the trigeminovascular system responses implicated in migraine (via 5-HT1D/5-HT1F receptors). Although the triptans represent the current mainstay of acute antimigraine treatment, a number of patients do not respond well to the triptans and are contraindicated in patients with cardiovascular pathologies.
Conclusion: This mini-review outlines further developments in the design of novel (non-vasoconstrictor) antimigraine treatments acting via 5-HT receptors, including selective agonists at 5-HT1D and 5-HT1F receptors, agonists at 5-HT1B/1D receptors combined with other properties as well as antagonists at 5-HT2B/2C, 5-HT3 and 5-HT7 receptors. It also touches upon the recent development of antagonists and antibodies at calcitonin gene-related peptide (CGRP) and its receptors, which produce a direct blockade of the CGRPergic vasodilator mechanisms involved in migraine. These alternative pharmacological approaches will hopefully lead to less side-effects.
Keywords: Antimigraine drugs, drug development, migraine, neurovascular disorder, triptans, 5-HT receptors.
Mini-Reviews in Medicinal Chemistry
Title:The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments
Volume: 17 Issue: 11
Author(s): Carlos M. Villalón*Antoinette Maassen VanDenBrink
Affiliation:
- Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F,Mexico
Keywords: Antimigraine drugs, drug development, migraine, neurovascular disorder, triptans, 5-HT receptors.
Abstract: Background: Migraine is a highly prevalent neurovascular disorder.
Objective: Of the many factors that have been implicated over the years, 5-hydroxytryptamine (5-HT; serotonin) has long been involved in the pathophysiology of migraine. Certainly, some lines of evidence suggest: (i) a 5-HT depletion from blood platelets resulting in cranial extracerebral vasodilatation; and (ii) the effectiveness of an intravenous (i.v.) infusion of 5-HT to abort migraine in some patients. More direct evidence comes from some drugs that influence 5-HT release and/or interact (as agonists or antagonists) with 5-HT receptors to treat this disorder. Indeed, the development of sumatriptan and second generation triptans in the 1990’s led to discover that these drugs produce selective cranial extracerebral vasoconstriction (via 5-HT1B receptors) and inhibition of the trigeminovascular system responses implicated in migraine (via 5-HT1D/5-HT1F receptors). Although the triptans represent the current mainstay of acute antimigraine treatment, a number of patients do not respond well to the triptans and are contraindicated in patients with cardiovascular pathologies.
Conclusion: This mini-review outlines further developments in the design of novel (non-vasoconstrictor) antimigraine treatments acting via 5-HT receptors, including selective agonists at 5-HT1D and 5-HT1F receptors, agonists at 5-HT1B/1D receptors combined with other properties as well as antagonists at 5-HT2B/2C, 5-HT3 and 5-HT7 receptors. It also touches upon the recent development of antagonists and antibodies at calcitonin gene-related peptide (CGRP) and its receptors, which produce a direct blockade of the CGRPergic vasodilator mechanisms involved in migraine. These alternative pharmacological approaches will hopefully lead to less side-effects.
Export Options
About this article
Cite this article as:
Villalón M. Carlos*, VanDenBrink Maassen Antoinette, The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments, Mini-Reviews in Medicinal Chemistry 2017; 17 (11) . https://dx.doi.org/10.2174/1389557516666160728121050
DOI https://dx.doi.org/10.2174/1389557516666160728121050 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Editorial (Thematic Issue: Stereoselective Synthesis and Applications of Compounds with N-O Bonds)
Current Organic Synthesis Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia
Current Neuropharmacology Subclinical Vitamin B12 Deficiency and Heart Rate Variability Across Life Cycle
Current Aging Science Evidence-Based Pharmacological Treatment of Substance Use Disorders and Pathological Gambling
Current Drug Abuse Reviews New Antipsychotics and Schizophrenia: A Review on Efficacy and Side Effects
Current Medicinal Chemistry Pediatric Heart Failure in the Developing World
Reviews on Recent Clinical Trials ACE Inhibitory Peptides Derived from Aquatic Protein
Current Protein & Peptide Science N-Methyl D-Aspartate (NMDA) Receptor Antagonists and Memantine Treatment for Alzheimer’s Disease, Vascular Dementia and Parkinson’s Disease
Current Alzheimer Research The Discovery and Development of Drug Combinations for the Treatment of Various Diseases from Patent Literature (1980-Present)
Current Topics in Medicinal Chemistry Patent Selections
Recent Patents on Cardiovascular Drug Discovery The RNA-Dependent-RNA Polymerase, an Emerging Antiviral Drug Target for the Hendra Virus
Current Drug Targets Vascularization of Engineered Tissues: Approaches to Promote Angiogenesis in Biomaterials
Current Topics in Medicinal Chemistry Combination of Therapeutic Hypothermia and Other Neuroprotective Strategies after An Ischemic Cerebral Insult
Current Neuropharmacology Therapeutic Angiogenesis in Ischemic Tissues by Growth Factors and Bone Marrow Mononuclear Cells Administration: Biological Foundation and Clinical Prospects
Current Stem Cell Research & Therapy Design, Development and Optimization of Ramipril Solid Lipid Nanoparticles Using Solvent Emulsification and Evaporation Method
Nanoscience & Nanotechnology-Asia Computational and Pharmacogenomic Insights on Hypertension Treatment: Rational Drug Design and Optimization Strategies
Current Drug Targets Genetically Redirected T Lymphocytes for Adoptive Immunotherapy of Solid Tumors
Current Gene Therapy Treating Nonthyroidal Illness Syndrome in the Critically Ill Patient: Still a Matter of Controversy
Current Drug Targets L-Arginine Transport in Disease
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Beneficial Effects of Corn Silk on Metabolic Syndrome
Current Pharmaceutical Design