{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:55:50Z","timestamp":1775912150286,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T00:00:00Z","timestamp":1599350400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>ANS\u20106637, an orally bioavailable selective and reversible aldehyde dehydrogenase\u20102 (ALDH2) inhibitor, is under development for drug and alcohol use disorders. During the elimination of alcohol, ALDH2 metabolizes acetaldehyde to acetate; inhibiting this enzyme can lead to aversive reactions due to the accumulation of acetaldehyde. Thus, understanding the safety and tolerability of ANS\u20106637 in combination with alcohol is essential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Design and Methods<\/jats:title><jats:p>Forty eight healthy males participated in a randomized, double\u2010blind, placebo\u2010controlled, single\u2010ascending dose cohort study of oral ANS\u20106637. Eligible participants were randomized to ANS\u20106637 (<jats:italic>n<\/jats:italic>\u00a0=\u00a036) or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) in a 3:1 fashion in each of 6 dose cohorts (8 per cohort; ANS\u20106637 dose levels were 25, 50, 100, 200, 400, and 600\u00a0mg). Two hours after receiving study drug, participants drank up to 5 standard drinks, 1 every 30\u00a0minutes. Safety assessments, pharmacodynamic measures, and pharmacokinetic blood samples were obtained.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Flushing was the most common adverse event (AE) associated with ANS\u20106637 (24 of 36 participants) compared with placebo (3 of 12). Statistically significant, but modest, increases in heart rate (HR) occurred (+10.5\u00a0bpm after 2 drinks; +16.9 to\u00a0+\u00a020.5\u00a0bpm after 3<jats:sup>rd<\/jats:sup> through 5<jats:sup>th<\/jats:sup> drink). No participant met HR or systolic blood pressure criteria for stopping ethanol administration. There were no clinically significant QTc interval prolongations. Individuals receiving ANS\u20106637 reported lower ratings of liking, alcohol effects, and feeling drunk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A single oral dose of ANS\u20106637 with up to 5 standards drinks over 2.5\u00a0hours was generally well tolerated in healthy males. The most common pharmacological response was flushing and an increase in HR, which are\u00a0known effects of acetaldehyde accumulation and consistent with inhibition of ALDH2 with oral ANS\u20106637 in combination with alcohol.\u00a0The results of this alcohol interaction study support further testing of ANS\u20106637 in individuals who consume alcohol heavily.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14416","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T19:14:33Z","timestamp":1595272473000},"page":"1885-1895","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Interaction of Ethanol and Oral ANS\u20106637, a Selective ALDH2 Inhibitor in Males: A Randomized, Double\u2010Blind, Placebo\u2010Controlled, Single\u2010Ascending Dose Cohort Study"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-2369","authenticated-orcid":false,"given":"Stephanie S.","family":"O\u2019Malley","sequence":"first","affiliation":[{"name":"From the Department of Psychiatry (SSO) Yale School of Medicine New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan J.","family":"Shram","sequence":"additional","affiliation":[{"name":"Altreos Research Partners (MJS, NL\u2010C) Toronto Ontario Canada"},{"name":"Department of Pharmacology and Toxicology (MJS) University of Toronto Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naama","family":"Levy\u2010Cooperman","sequence":"additional","affiliation":[{"name":"Altreos Research Partners (MJS, NL\u2010C) Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley","family":"Vince","sequence":"additional","affiliation":[{"name":"Altasciences\/Vince Associates (BV) Overland Park Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter M.","family":"Strumph","sequence":"additional","affiliation":[{"name":"Amygdala Neurosciences, Inc (PMS, ID, BKB) San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Diamond","sequence":"additional","affiliation":[{"name":"Amygdala Neurosciences, Inc (PMS, ID, BKB) San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent K.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Amygdala Neurosciences, Inc (PMS, ID, BKB) San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,6]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Amygdala Neurosciences Inc.(Data on file.) 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