New therapeutic target in primary headaches - blocking theCGRP receptor

Expert Opin Ther Targets. 2003 Jun;7(3):377-83. doi: 10.1517/14728222.7.3.377.

Abstract

The primary headaches are among the most prevalent neurological disorders, afflicting up to 16% of the adult population. The associated pain originates from intracranial blood vessels that are innervated by sensory nerves storing several neurotransmitters. In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP), but not other neuronal messengers. The specific purpose of this review is to describe CGRP in the human cranial circulation and to elucidate a possible role for a specific antagonist in the treatment of primary headaches. Acute treatment with administration of a 5-HT(1B/1D) agonist (triptan) results in alleviation of the headache and normalisation of the CGRP level. The mechanism of action of triptans involves vasoconstriction of intracranial vessels and a presynaptic inhibitory effect of sensory nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small-molecule CGRP antagonists, which are predicted to have fewer cardiovascular side effects in comparison to the triptans. The initial pharmacological profile of such a group of compounds has recently been disclosed. These compounds have high selectivity for human CGRP receptors and are reportedly efficacious in the relief of acute attacks of migraine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Analgesics, Non-Narcotic / chemistry
  • Analgesics, Non-Narcotic / pharmacology*
  • Analgesics, Non-Narcotic / therapeutic use
  • Animals
  • Calcitonin / antagonists & inhibitors
  • Calcitonin / physiology
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Child
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Headache / drug therapy*
  • Headache / physiopathology
  • Humans
  • Migraine Disorders / drug therapy
  • Migraine Disorders / physiopathology
  • Neurotransmitter Agents
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein Precursors / antagonists & inhibitors
  • Protein Precursors / physiology
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use
  • Rats
  • Receptors, Calcitonin Gene-Related Peptide / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Trigeminal Nerve / physiopathology
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Analgesics, Non-Narcotic
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Neurotransmitter Agents
  • Piperazines
  • Protein Precursors
  • Quinazolines
  • Receptors, Calcitonin Gene-Related Peptide
  • Calcitonin
  • olcegepant