{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:11:04Z","timestamp":1791303064444,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T00:00:00Z","timestamp":1427414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Background and Purpose<\/jats:title>Calcitonin gene\u2010related peptide (CGRP<\/jats:styled-content>) plays an important role in the pathology of migraine, and recent clinical trials suggest the inhibition of CGRP<\/jats:styled-content>\u2010mediated processes as a new therapeutic option in migraine. In this study, we describe the generation of NOX<\/jats:styled-content>\u2010L<\/jats:styled-content>41, a CGRP<\/jats:styled-content>\u2010neutralizing mirror\u2010image (l<\/jats:sc>\u2010)aptamer (S<\/jats:styled-content>piegelmer) and investigate its in vitro<\/jats:italic><\/jats:styled-content> and in vivo<\/jats:italic><\/jats:styled-content> function.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>A CGRP<\/jats:styled-content>\u2010binding S<\/jats:styled-content>piegelmer was identified by in vitro<\/jats:italic><\/jats:styled-content> selection. Binding studies were performed using surface plasmon resonance (SPR<\/jats:styled-content>), and the inhibitory activity was determined in cell\u2010based assays. The pharmacokinetic profile comparing i.v. and s.c. dosing was analysed in rats. Intravital two\u2010photon microscopy was employed to follow extravasation from meningeal vessels. Finally, in vivo<\/jats:italic><\/jats:styled-content> efficacy was tested in a model of electrically evoked meningeal plasma protein extravasation (PPE<\/jats:styled-content>) in rats.<\/jats:p><\/jats:sec>Key Results<\/jats:title>We identified NOX<\/jats:styled-content>\u2010L<\/jats:styled-content>41, a novel CGRP<\/jats:styled-content>\u2010neutralizing S<\/jats:styled-content>piegelmer. SPR<\/jats:styled-content> studies showed that NOX<\/jats:styled-content>\u2010L<\/jats:styled-content>41 binds to human and rat\/mouse CGRP<\/jats:styled-content> with sub\u2010nanomolar affinities and is highly selective against related peptides such as amylin. In vitro<\/jats:italic><\/jats:styled-content>, NOX<\/jats:styled-content>\u2010L<\/jats:styled-content>41 effectively inhibited CGRP<\/jats:styled-content>\u2010induced cAMP<\/jats:styled-content> formation in SK<\/jats:styled-content>\u2010N<\/jats:styled-content>\u2010MC<\/jats:styled-content> cells. In rats, NOX<\/jats:styled-content>\u2010L<\/jats:styled-content>41 had a plasma half\u2010life of 8\u2009h. Pharmacodynamic studies showed that NOX<\/jats:styled-content>\u2010L<\/jats:styled-content>41 extravasates from blood vessels in the dura mater and inhibits neurogenic meningeal PPE<\/jats:styled-content> for at least 18\u2009h after single dosing.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>This is the first description of the CGRP<\/jats:styled-content>\u2010neutralizing S<\/jats:styled-content>piegelmer NOX<\/jats:styled-content>\u2010L<\/jats:styled-content>41. Preclinical studies confirmed a role for CGRP<\/jats:styled-content> in neurogenic PPE<\/jats:styled-content> and provided proof\u2010of\u2010concept for the potential use of this new drug candidate for the treatment or prevention of migraine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13110","type":"journal-article","created":{"date-parts":[[2015,2,9]],"date-time":"2015-02-09T07:11:04Z","timestamp":1423465864000},"page":"3086-3098","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A novel CGRP<\/scp>\u2010neutralizing S<\/scp>piegelmer attenuates neurogenic plasma protein extravasation"],"prefix":"10.1111","volume":"172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4638-4826","authenticated-orcid":false,"given":"K","family":"Hoehlig","sequence":"first","affiliation":[{"name":"NOXXON Pharma AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K 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