Calcitonin Gene Related Peptide Receptor Antagonist

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Calcitonin-Gene-Related-Peptide-Receptor Antagonists ( CGRP-Receptor -Antagonists or CGRP-Antagonists for short ) are drugs that reduce the effect of the Calcitonin-Gene-Related Peptide (CGRP) by blocking its receptor , the Calcitonin-Gene-Related-Peptide-Receptor , inhibit. As antagonists , they cancel out the vasodilating properties of the calcitonin gene-related peptide.

A potential use in the acute therapy of migraines is based on the observation that calcitonin-gene-related-peptide-receptor antagonists lead to a narrowing of the meningeal blood vessels that are pathologically enlarged during a migraine attack . This knowledge led to the development of two groups of active ingredients:

Small molecules

The efficacy of the calcitonin gene-related peptide receptor antagonists Olcegepant and Telcacepant has been successfully tested in clinical studies . However, development of Olcegepant was discontinued due to poor oral bioavailability. Telcagepant was the first orally active calcitonin gene-related peptide receptor antagonist to be investigated in clinical studies. However, the clinical development was not continued due to increased liver values ​​with long-term use. The active ingredients Ubrogepant and Rimegepant are in clinical development for the acute therapy of migraines.

Monoclonal antibodies

The effectiveness of the monoclonal antibodies erenumab , eptinezumab , fremanezumab and galcanezumab for migraine prophylaxis has been successfully tested in clinical studies . Eptinezumab, fremanezumab, and galcanezumab target the calcitonin gene-related peptide (CGRP) directly , while erenumab blocks the calcitonin gene-related peptide receptor .

Individual evidence

  1. ^ SJ Tepper, MJ Stillman: Clinical and preclinical rationale for CGRP-receptor antagonists in the treatment of migraine . In: Headache . Vol. 48, No. 8 , December 2008, pp. 1259-1268 , doi : 10.1111 / j.1526-4610.2008.01214.x .
  2. ↑ Lanfranco Pellesi, Simona Guerzoni, Luigi Alberto Pini: Spotlight on Anti-CGRP Monoclonal Antibodies in Migraine: The Clinical Evidence to Date . In: Clinical Pharmacology in Drug Development . tape 6 , no. 6 , 2017, p. 534-547 , doi : 10.1002 / cpdd.345 , PMID 28409893 , PMC 5697612 (free full text).
  3. ↑ UBRELVY- ubrogepant tablet . DailyMed .
  4. ↑ NURTEC ODT- rimegepant sulfate tablet, orally disintegrating . DailyMed .
  5. ^ Philip R. Holland, Peter J. Goadsby: Targeted CGRP Small Molecule Antagonists for Acute Migraine Therapy . In: Neurotherapeutics . tape 15 , no. 2 , April 2018, p. 304-312 , doi : 10.1007 / s13311-018-0617-4 , PMID 29556965 , PMC 5935646 (free full text).
  6. ↑ New drugs: Fremanezumab (Ajovy®) , drug prescription in practice online in advance on July 9, 2019, accessed on July 9, 2019
  7. ↑ New drugs: Galcanezumab , AKDAE: Drug Ordinance in Practice, accessed on May 2, 2019
  8. ↑ Petra Jungmayr: Targeted against migraines . In: DAZ.online . July 12, 2018 ( deutsche-apotheker-zeitung.de [accessed September 25, 2018]).