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CGRP is also present in the human heart, acts via CGRP receptors, and has been shown to increase the force of contraction (FOC) in isolated, electrically driven human atrial preparations (HAP) from adult patients obtained during open-heart surgery. Here, the hypothesis was tested that the positive inotropic effect (PIE) of CGRP could be attenuated by three anti-migraine drugs, namely ubrogepant, erenumab (both CGRP receptor antagonists), and eptinezumab (a CGRP antagonist). CGRP, cumulatively applied at concentrations ranging from 1 to 100 nM, increased the FOC. In the presence of cilostamide, an inhibitor of phosphodiesterase III, CGRP was more potent and effective than in the absence of cilostamide. Furthermore, when 100 nM CGRP was administered, subsequent application of ubrogepant (1 nM), erenumab (2 nM), and eptinezumab (6 nM) led to a reduction of FOC in HAP. In a more effective way, 1 \u00b5M carbachol and 1 \u00b5M (-)-N<jats:sup>6<\/jats:sup>-phenylisopropyladenosine (PIA) attenuated the PIE of CGRP in the presence of cilostamide. Conversely, when we applied first ubrogepant (1 nM), erenumab (2 nM), or eptinezumab (6 nM), then, this pre-incubation attenuated the PIE in HAP of cumulatively applied CGRP compared to CGRP given alone. We conclude that ubrogepant, erenumab, and eptinezumab are functional antagonists of CGRP in HAP at therapeutic concentrations of these anti-migraine drugs. Further investigation is necessary to determine whether this reduction in FOC is beneficial or detrimental for migraine patients.<\/jats:p>","DOI":"10.1007\/s00210-025-04029-7","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T04:53:07Z","timestamp":1741927987000},"page":"11909-11918","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene\u2013related peptide in the isolated human atrium"],"prefix":"10.1007","volume":"398","author":[{"given":"Joachim","family":"Neumann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Gergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"4029_CR1","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1007\/BF00512942","volume":"333","author":"M B\u00f6hm","year":"1986","unstructured":"B\u00f6hm M, Mende U, Schmitz W, Scholz H (1986) Increased sensitivity to alpha-adrenoceptor stimulation but intact purinergic and muscarinergic effects in prehypertensive cardiac hypertrophy of spontaneously hypertensive rats. 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