{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:48:14Z","timestamp":1788994094306,"version":"build-2803163510"},"reference-count":12,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2023,12]]},"abstract":"\n Objective<\/jats:title>\n \n Preclinical and clinical studies implicate the vascular ATP-sensitive potassium (K\n ATP<\/jats:sub>\n ) channel in the signaling cascades underlying headache and migraine. However, attempts to demonstrate that the K\n ATP<\/jats:sub>\n channel inhibitor glibenclamide would attenuate triggered headache in healthy volunteers have proven unsuccessful. It is questionable, however, whether target engagement was achieved in these clinical studies.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Literature data for human glibenclamide pharmacokinetics, plasma protein binding and functional IC\n 50<\/jats:sub>\n values were used to predict the K\n ATP<\/jats:sub>\n receptor occupancy (RO) levels obtained after glibenclamide dosing in the published exploratory clinical headache provocation studies. RO vs. time profiles of glibenclamide were simulated for the pancreatic K\n ATP<\/jats:sub>\n channel subtype Kir6.2\/SUR1 and the vascular subtype Kir6.1\/SUR2B.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n At the clinical dose of 10\u2009mg of glibenclamide used in the headache provocation studies, predicted maximal occupancy levels of up to 90% and up to 26% were found for Kir6.2\/SUR1 and Kir6.1\/SUR2B, respectively.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The findings of the present study indicate that effective Kir6.1\/SUR2B target engagement was not achieved in the clinical headache provocation studies using glibenclamide. Therefore, development of novel selective Kir6.1\/SUR2B inhibitors, with good bioavailability and low plasma protein binding, is required to reveal the potential of K\n ATP<\/jats:sub>\n channel inhibition in the treatment of migraine.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/03331024231219475","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T12:24:56Z","timestamp":1702038296000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["The shortcoming of using glibenclamide in exploratory clinical headache provocation studies"],"prefix":"10.1177","volume":"43","author":[{"given":"Palle","family":"Christophersen","sequence":"first","affiliation":[{"name":"Saniona A\/S, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-0577","authenticated-orcid":false,"given":"Tino","family":"Dyhring","sequence":"additional","affiliation":[{"name":"Saniona A\/S, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"bibr1-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002008"},{"key":"bibr2-03331024231219475","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152406"},{"key":"bibr3-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20959294"},{"key":"bibr4-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420949863"},{"key":"bibr5-03331024231219475","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.652136"},{"key":"bibr6-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1177\/03331024221080574"},{"key":"bibr7-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-023-01350-y"},{"key":"bibr8-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197634"},{"key":"bibr9-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1990.tb03688.x"},{"key":"bibr10-03331024231219475","doi-asserted-by":"publisher","DOI":"10.3390\/ph16020225"},{"key":"bibr11-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03172-7"},{"key":"bibr12-03331024231219475","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169252"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024231219475","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024231219475","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024231219475","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:45:29Z","timestamp":1777387529000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.sagepub.com\/doi\/10.1177\/03331024231219475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":12,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1177\/03331024231219475"],"URL":"https:\/\/doi.org\/10.1177\/03331024231219475","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12]]},"article-number":"03331024231219475"}}