Side effects associated with current and prospective antimigraine pharmacotherapies

Expert Opin Drug Metab Toxicol. 2018 Jan;14(1):25-41. doi: 10.1080/17425255.2018.1416097. Epub 2017 Dec 15.

Abstract

Migraine is a neurovascular disorder. Current acute specific antimigraine pharmacotherapies target trigeminovascular 5-HT1B/1D, 5-HT1F and CGRP receptors but, unfortunately, they induce some cardiovascular and central side effects that lead to poor treatment adherence/compliance. Therefore, new antimigraine drugs are being explored. Areas covered: This review considers the adverse (or potential) side effects produced by current and prospective antimigraine drugs, including medication overuse headache (MOH) produced by ergots and triptans, the side effects observed in clinical trials for the new gepants and CGRP antibodies, and a section discussing the potential effects resulting from disruption of the cardiovascular CGRPergic neurotransmission. Expert opinion: The last decades have witnessed remarkable developments in antimigraine therapy, which includes acute (e.g. triptans) and prophylactic (e.g. β-adrenoceptor blockers) antimigraine drugs. Indeed, the triptans represent a considerable advance, but their side effects (including nausea, dizziness and coronary vasoconstriction) preclude some patients from using triptans. This has led to the development of the ditans (5-HT1F receptor agonists), the gepants (CGRP receptor antagonists) and the monoclonal antibodies against CGRP or its receptor. The latter drugs represent a new hope in the antimigraine armamentarium, but as CGRP plays a role in cardiovascular homeostasis, the potential for adverse cardiovascular side effects remains latent.

Keywords: 5-HT); Adverse side effects; CGRP; antimigraine drugs; headache; lasmiditan; migraine; serotonin(5-hydroxytryptamine; triptans.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Drug Design*
  • Headache Disorders, Secondary / etiology
  • Humans
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / physiopathology
  • Receptor, Serotonin, 5-HT1F
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / adverse effects
  • Serotonin Receptor Agonists / pharmacology
  • Tryptamines / administration & dosage
  • Tryptamines / adverse effects
  • Tryptamines / pharmacology

Substances

  • Antibodies, Monoclonal
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Tryptamines