{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:34:52Z","timestamp":1763534092622},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lasmiditan (LY573144\/COL\u2010144) is a high\u2010affinity, centrally penetrant, selective 5\u2010HT<jats:sub>1F<\/jats:sub> receptor agonist currently under investigation for acute treatment of migraine. Although lasmiditan is not known to induce vasoconstriction, it remains important to understand its effect on cardiovascular parameters because it is likely to be coadministered with \u03b2\u2010adrenergic receptor antagonists used for migraine prophylaxis, such as propranolol. This phase 1, single\u2010center, open\u2010label, fixed\u2010sequence study evaluated the cardiovascular and pharmacokinetic effects of 200\u00a0mg lasmiditan in 44 healthy subjects receiving repeated oral doses of twice\u2010daily 80\u00a0mg propranolol under fasting conditions. Coadministration caused statistically significant decreases in mean hourly heart rate relative to propranolol alone, but the maximum magnitude of this effect was \u20136.5 bpm and recovered to predose levels by 3 to 4\u00a0hours before stabilizing. Additionally, short\u2010lived (\u22642.5\u00a0hours) statistically significant increases in systolic blood pressure (8.3 mm Hg) and diastolic blood pressure (6.4 mm Hg) were observed following coadministration. Consistent with the largely nonoverlapping metabolic pathways of lasmiditan and propranolol, exposure to either drug was not affected by coadministration. Overall, compared with administration of either drug alone, coadministration was generally well tolerated.<\/jats:p>","DOI":"10.1002\/cpdd.768","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T04:24:47Z","timestamp":1579235087000},"page":"629-638","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effects of Lasmiditan on Cardiovascular Parameters and Pharmacokinetics in Healthy Subjects Receiving Oral Doses of Propranolol"],"prefix":"10.1002","volume":"9","author":[{"given":"Max","family":"Tsai","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Case","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Ardayfio","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Hochstetler","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Wilbraham","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285614562419"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2017.1280457"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2017.1361406"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13582"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006641"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-0974-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-1032-x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419855080"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102410370873"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000159639.59770.36"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-014-3107-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102414550416"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2019.1578749"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DHPS.S151073"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2016.1154042"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1975176709"},{"issue":"6","key":"e_1_2_9_18_1","first-page":"909","article-title":"Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. 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