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
Drugs and mitochondria
Mitochondria play a central role in the life and death of cells. They are not merely the center for energy metabolism but are also the headquarters for different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Mitochondria maintain homeostasis in the cell by interacting with reactive oxygen-nitrogen species ...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
-
Adipobiology for Novel Therapeutic Approaches in Metabolic Syndrome
Current Vascular Pharmacology Drugs for AIDS
Mini-Reviews in Medicinal Chemistry The Diagnosis of Large Airway Pathology and the Role of Rigid Bronchoscopy
Current Respiratory Medicine Reviews Treatment of Catatonia with Asenapine in a Patient with Schizotypal Personality Disorder, Psychotic Depression and Septic Shock from SARSCoV- 2 - A Case Report
CNS & Neurological Disorders - Drug Targets To Be-et, or Not to Be-et, That is the Question: The Role(s) of Nitrate and Nitrite in Health and Illness
Reviews on Recent Clinical Trials Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Advanced Thyroid Cancer
Recent Patents on Anti-Cancer Drug Discovery Recent Advances in Exercise Testing
Current Cardiology Reviews Review of Rational Approaches to the Treatment of Pain Management-Role forOpioids Therapies
Current Drug Therapy Pharmacological Strategies for Neuroprotection in Traumatic Brain Injury
Mini-Reviews in Medicinal Chemistry Industrial Chemicals and Acute Lung injury with a Focus on Exposure Scenarios
Current Respiratory Medicine Reviews Gender Differences in Pharmacokinetics and Side Effects of Second Generation Antipsychotic Drugs
Current Neuropharmacology State of the Art Management of Transfusion-Related Acute Lung Injury (TRALI)
Current Pharmaceutical Design The Paths to Neurodegeneration in Genetic Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Targeting Nanoparticles as Drug Delivery Systems for Cancer Treatment
Current Nanoscience Cardiovascular Pharmacogenetics of Antihypertensive and Lipid- Lowering Therapies
Current Molecular Medicine A Case Report of Necrotizing Fasciitis after Cesarean Delivery
Current Women`s Health Reviews Clinical Uses of Melatonin: Evaluation of Human Trials
Current Medicinal Chemistry Physiological Significance and Therapeutic Potential of Adrenomedullin in Pulmonary Hypertension
Cardiovascular & Hematological Disorders-Drug Targets New Approaches on Leishmaniasis Treatment and Prevention: A Review of Recent Patents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Inhalation Gases or Gaseous Mediators As Neuroprotectants for Cerebral Ischaemia
Current Drug Targets