Neue Therapieoptionen bei Migräne

Zusammenfassung

Calcitonin gene-related peptide (CGRP), ein von primären Afferenzen freigesetztes vasoaktives Neuropeptid, steht im Fokus der pharmakologischen Migränetherapie. CGRP hat Wirkungen auf viele zentrale und periphere Funktionen, aber der migränefördernde Wirkungsmechanismus ist unklar. Derzeitige klinische und experimentelle Therapieprinzipien beruhen auf der Hemmung der CGRP-Freisetzung durch 5-HT1B/D-Agonisten (Triptane) oder der CGRP-Rezeptoren durch nicht peptidische Antagonisten (Gepante). Triptane sind bei einer Reihe von Patienten nicht ausreichend wirksam und können bei zu häufiger Anwendung einen Kopfschmerz bei Medikamentenübergebrauch verursachen, während die Weiterentwicklung der Gepante wegen lebertoxischer Nebenwirkungen unterbrochen worden ist. Neue hoffnungsvolle Entwicklungen in der Migränetherapie sind CGRP oder CGRP-rezeptorenblockierende monoklonale Antikörper, die in ersten klinischen Studien bei chronischer und häufiger Migräne geprüft worden sind. In diesem Übersichtsartikel werden die bekannten Wirkungen von CGRP in und außerhalb des trigeminalen Systems beleuchtet und auf dem Hintergrund der therapeutischen Effektivität sowie möglicher Nebenwirkungen bei der Blockierung des CGRP-Systems kritisch diskutiert.

Summary

Pharmacotherapy of migraine pain has largely been focused on calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide mainly released from activated primary afferents. CGRP has multiple effects in different central and peripheral systems but its migraine promoting actions are largely unclear. Current clinical and experimental principles are based on reducing stimulated CGRP release by 5-HT1B/D agonists (triptans) or inhibiting CGRP receptors by non-peptide antagonists (gepants). Triptans are ineffective in a variety of patients and their frequent use may cause medication overuse headache, while further development of gepants has been interrupted due to liver toxic effects. Development and clinical trials of humanized monoclonal antibodies targeting CGRP or its receptors appear promising as a new strategy in the therapy of the growing problem of chronic migraine. This review discusses critically the sites and effects of CGRP receptor activation and inhibition within and outside of the trigeminal system relevant for the efficacy and safety of preventive therapeutic strategies targeting CGRP signaling.

Schlüsselwörter

Chronische Migräne - Calcitonin gene-related peptide - CGRP-Antagonisten - monoklonale Antikörper

Keywords

Chronic migraine - calcitonin gene-related peptide - CGRP antagonists - monoclonal antibodies

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