{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:17:14Z","timestamp":1790648234589,"version":"4.1.0"},"reference-count":62,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Despite recent advances in migraine treatment there is a need for therapies with higher clinical efficacy and\/or fewer side effects. Triptans (5-HT\n                      <jats:sub>1B\/1D\/1F<\/jats:sub>\n                      agonists) are essential in the present treatment regime and gepants (CGRP-receptor antagonists) are recognized as effective in acute migraine treatment. Triptans and gepants have different mechanisms of action and here we tested the hypothesis that a combination of these drugs (sumatriptan and olcegepant) would result in an additive effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the validated glyceryl trinitrate mouse model of migraine, we initially tested dose-response relationships of sumatriptan (0.1, 0.3, and 0.6\u2009mg\/kg IP) and olcegepant (0.25, 0.50, and 1.0\u2009mg\/kg IP) to find suitable high and low doses. Subsequently, we performed a combination study of the two drugs with a low and a high dose. All experiments were vehicle (placebo) controlled and blinded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sumatriptan significantly reduced glyceryl trinitrate-induced allodynia (F(4,54)\u2009=\u200913.51, p\u2009&lt;\u20090.0001) at all doses. Olcegepant also reduced glyceryl trinitrate-induced allodynia (F(4,53)\u2009=\u200916.11, p\u2009&lt;\u20090.0001) with the two higher doses being significantly effective. Combining 0.50\u2009mg\/kg olcegepant with 0.1 or 0.6\u2009mg\/kg sumatriptan did not have any improved effect compared to either drug alone ( p\u2009&gt;\u20090.50 on all days) in our mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining olcegepant and sumatriptan did not have an additive effect compared to single-drug treatment in this study. Triptan-gepant combinations will therefore most likely not improve migraine treatment. Nevertheless, further studies are necessary, and combinations should also be examined in patients with migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0333102420963857","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:39:11Z","timestamp":1602808751000},"page":"329-339","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":33,"title":["No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-1902","authenticated-orcid":false,"given":"Charlotte","family":"Ernstsen","sequence":"first","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes","family":"Olesen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark"},{"name":"University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail) \u2013 UMR_S 1085, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"bibr1-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2015"},{"key":"bibr2-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1712559"},{"key":"bibr3-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1111\/head.13444"},{"key":"bibr4-0333102420963857","doi-asserted-by":"crossref","unstructured":"The Lancet Neurology. \nComplicated decisions on new migraine-prevention therapies.\n                      Lancet Neurol\n                      2019; \n18: 221.","DOI":"10.1016\/S1474-4422(19)30041-9"},{"key":"bibr5-0333102420963857","doi-asserted-by":"publisher","DOI":"10.2165\/11630590-000000000-00000"},{"key":"bibr6-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra010917"},{"key":"bibr7-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14832"},{"key":"bibr8-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1177\/0333102412451356"},{"key":"bibr9-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0003-1"},{"key":"bibr10-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-008-0011-4"},{"key":"bibr11-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2017.1288721"},{"key":"bibr12-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2004.00694.x"},{"key":"bibr13-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-011-0309-5"},{"key":"bibr14-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00404.x"},{"key":"bibr15-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030505"},{"key":"bibr16-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b87942"},{"key":"bibr17-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703110"},{"key":"bibr18-0333102420963857","unstructured":"U.S. Food & Drug Administration. FDA approves new treatment for adults with migraine (press release), https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-new-treatment-adults-migraine (23 December 2019, accessed 10 February 2020)."},{"key":"bibr19-0333102420963857","unstructured":"Allergan. Allergan recieves U.S. FDA approval for Ubrelvy\u2122 for acute treatment of migraine with or without aura in adults (press release), https:\/\/www.allergan.com\/News\/Details\/2019\/12\/Allergan-Receives-US-FDA-Approval (23 December 2019, accessed 10 February 2020)."},{"key":"bibr20-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813049"},{"key":"bibr21-0333102420963857","unstructured":"Biohaven Pharmaceuticals. 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Sumatriptan does not antagonize CGRP-induced symptoms in healthy volunteers.\n                      Headache\n                      2020; 60: 665\u2013676.","DOI":"10.1111\/head.13747"},{"key":"bibr54-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8090-9-52"},{"key":"bibr55-0333102420963857","first-page":"24","volume":"37","author":"Savarese JJ","year":"2017","journal-title":"Multimodal analgesia as an alternative to the risks of opioid monotherapy in surgical pain management"},{"key":"bibr56-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1016\/j.anclin.2017.01.018"},{"key":"bibr57-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2015.08.012"},{"key":"bibr58-0333102420963857","author":"Curto M","year":"2019","journal-title":"Expert Opin Pharmacother"},{"key":"bibr59-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001801"},{"key":"bibr60-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1081"},{"key":"bibr61-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90654-4"},{"key":"bibr62-0333102420963857","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23768"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0333102420963857","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0333102420963857","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0333102420963857","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:48:55Z","timestamp":1777387735000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0333102420963857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,15]]},"references-count":62,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1177\/0333102420963857"],"URL":"https:\/\/doi.org\/10.1177\/0333102420963857","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,15]]}}}