CGRP als therapeutisches Ziel in der Therapie von primären Kopfschmerzen

Zusammenfassung

Calcitonin gene related peptide (CGRP) übernimmt eine wichtige Rolle in der Pathophysiologie von primären Kopfschmerzerkrankungen in seiner Funktion als potenter Vasodilatator und Neuromodulator. Mehrere Studien konnten eine Beteiligung von CGRP bei der Migräne und beim Clusterkopfschmerz nachweisen, der genaue Wirkmechanismus ist jedoch noch unklar. Die in der Migränetherapie zur Verfügung stehenden Akutmedikamente wie Triptane und die zur Migräneprophylaxe eingesetzten Medikamente sind bei vielen Patienten nicht ausreichend wirksam oder sind durch ihre Nebenwirkungen bzw. Kontraindikationen limitiert. Neue Therapiemöglichkeiten könnten Medikamente sein, die direkt in die durch CGRP vermittelten Mechanismen eingreifen. Derzeit befinden sich in der klinischen Entwicklung zur Akuttherapie der Migräne die CGRP-Rezeptorantagonisten, die sogenannten Gepante. Deren Anwendung könnte jedoch aufgrund von einer eventuellen Lebertoxizität limitiert sein. Die Effektivität der CGRP oder CGRP-Rezeptor blockierenden monoklonalen Antikörper in der Prophylaxe der Migräne wurde in mehreren klinischen Studien untersucht. Diese Substanzen könnten vielversprechende neue Optionen in der Migränetherapie darstellen. In diesem Artikel werden die pathophysiologischen und klinischen Grundlagen einer Beteiligung von CGRP im Mechanismus von primären Kopfschmerzen dargestellt, die akutellen Daten zur Effektivität der genannten Substanzen aufgeführt und mögliche Nebenwirkungen einer Langzeitblockade des CGRP-Systems diskutiert.

Summary

Calcitonin gene related peptide (CGRP) plays a key role in the pathophysiology of primary headache disorders as a potent vasodilatator and neuromodulator. Various studies demonstrated an involvement of CGRP in migraine and in cluster headache. However, its detailed mechanism of action remains unclear. Current drugs used in acute migraine treatment such as triptans and those used for migraine prevention have limited efficacy in a variety of patients or are restricted by their side effects or contraindications. Possible new treatment options include drugs that interact directly with CGRP mediated mechanisms. To date, CGRP receptor antagonists are assessed in the acute treatment of migraine, yet, their application might be restricted due to liver toxicity. The efficacy of CGRP or CGRP receptor blocking monoclonal antibodies in the prophylaxis of migraine was demonstrated in various clinical studies. These substances might represent promising new options in migraine treatment. This review illustrates pathophysiological and clinical principles of the contribution of CGRP in the mechanisms of primary headaches. Latest data regarding the efficacy of these substances will be presented and possible side effects of long-term blockade of the CGRP system will be discussed.

Schlüsselwörter

Calcitonin gene related peptide - Migräne - CGRP-Rezeptorantagonisten - monoklonale Antikörper

Keywords

Calcitonin gene related peptide - migraine - CGRP receptor antagonists - monoclonal antibodies

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