title: The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F, Mexico.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam. Netherlands.
authors.forename: Antoinette Maassen
authors.initials: AM
authors.lastname: VanDenBrink
mesh_terms: D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D012701:Serotonin / Q000737:chemistry / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C108218:4-fluoro-N-(3-(1-methyl-4-piperidinyl)-1H-indol-5-yl)benzamide; D001549:Benzamides; D007211:Indoles; D010880:Piperidines; D011725:Pyridines; D044346:Receptor, Serotonin, 5-HT1D; D058825:Serotonin 5-HT1 Receptor Agonists; D012701:Serotonin; C554777:lasmiditan
keywords: 5-HT receptors; Antimigraine drugs; drug development; migraine; neurovascular disorder; triptans