Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital

No central action of CGRP antagonising drugs in the GTN mouse model of migraine

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. The effect of pituitary adenylate cyclase-activating peptide-38 and vasoactive intestinal peptide in cluster headache

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Neurofilament light chain as biomarker in idiopathic intracranial hypertension

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Functional gene networks reveal distinct mechanisms segregating in migraine families

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Letter to the editor regarding proposed new diagnostic criteria for migraine

    Publikation: Bidrag til tidsskriftLetterForskningpeer review

  4. Sumatriptan Does Not Antagonize CGRP-Induced Symptoms in Healthy Volunteers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

INTRODUCTION: Clinically, calcitonin gene-related peptide antagonising drugs are recognized as effective in migraine treatment, but their site of action is debated. Only a small fraction of these compounds pass the blood-brain barrier and accesses the central nervous system. Regardless, it has been argued that the central nervous system is the site of action. Here, we test this hypothesis by bypassing the blood-brain barrier through intracerebroventricular injection of calcitonin gene-related peptide antagonising drugs.

METHODS: We used the glyceryl trinitrate (GTN) mouse model, which is well validated by its response to specific migraine drugs. The calcitonin gene-related peptide receptor antagonist olcegepant and the calcitonin gene-related peptide monoclonal antibody ALD405 were administered either intraperitoneally or intracerebroventricularly. The outcome measure was cutaneous mechanical allodynia.

RESULTS: Mice given olcegepant intraperitoneally + GTN on day 1 had a mean 50% withdrawal threshold of 1.2 g in contrast to mice receiving placebo + GTN, which had a threshold of 0.3 g (p < 0.001). Similarly, in the ALD405 + GTN group, mice had thresholds of 1.2 g versus 0.2 g in the placebo + GTN group (p < 0.001). However, both drugs were ineffective when delivered intracerebroventricularly, as control and active groups had identical mechanical sensitivity thresholds, 0.2 g versus 0.1 g and 0.1 g versus 0.1 g for olcegepant and ALD405, respectively (p > 0.99 in both cases).

DISCUSSION: The site of action of olcegepant and of the monoclonal antibody ALD405 is outside the blood-brain barrier in this mouse model of migraine. It is likely that these results can be generalised to all gepants and all antibodies and that the results are relevant for human migraine.

TidsskriftCephalalgia : an international journal of headache
Udgave nummer9
Sider (fra-til)924-934
Antal sider11
StatusUdgivet - aug. 2020

ID: 60054621