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A range of analogues and derivatives has been investigated over the years, including those classified as new psychoactive substances. This study presents the characterization of the novel lysergamide <jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2010diethyl\u20101\u2010propanoyl\u20106\u2010(prop\u20102\u2010en\u20101\u2010yl)\u20109,10\u2010didehydroergoline\u20108\u03b2\u2010carboxamide (1P\u2010AL\u2010LAD) using various mass spectrometric, gas\u2010 and liquid chromatographic and spectroscopic methods. In vitro metabolism studies using pooled human liver microsomes (pHLM) confirmed that 1P\u2010AL\u2010LAD converted to AL\u2010LAD as the most abundant metabolite consistent with the hypothesis that 1P\u2010AL\u2010LAD may act as a prodrug. Fourteen metabolites were detected in total; metabolic reactions included hydroxylation of the core lysergamide ring structure or the <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>\u2010allyl group, formation of dihydrodiol metabolites, <jats:italic>N<\/jats:italic>\u2010dealkylation, <jats:italic>N<\/jats:italic><jats:sup>1<\/jats:sup>\u2010deacylation, dehydrogenation, and combinations thereof. The in vivo behavioral activity of 1P\u2010AL\u2010LAD was evaluated using the mouse head twitch response (HTR), a 5\u2010HT<jats:sub>2A<\/jats:sub>\u2010mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. 1P\u2010AL\u2010LAD induced a dose\u2010dependent increase in HTR counts with an inverted U\u2010shaped dose\u2013response function, similar to lysergic acid diethylamide (LSD), psilocybin, and other psychedelics. Following intraperitoneal injection, the median effective dose (ED<jats:sub>50<\/jats:sub>) for 1P\u2010AL\u2010LAD was 491\u2009nmol\/kg, making it almost three times less potent than AL\u2010LAD (174.9\u00a0nmol\/kg). Previous studies have shown that <jats:italic>N<\/jats:italic><jats:sup>1<\/jats:sup>\u2010substitution disrupts the ability of lysergamides to activate the 5\u2010HT<jats:sub>2A<\/jats:sub> receptor; based on the in vitro metabolism data, 1P\u2010AL\u2010LAD may induce the HTR because it acts as a prodrug and is metabolized to AL\u2010LAD after administration to mice.<\/jats:p>","DOI":"10.1002\/dta.3281","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T02:09:38Z","timestamp":1651889378000},"page":"1503-1518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P\u2010AL\u2010LAD"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8632-5372","authenticated-orcid":false,"given":"Simon D.","family":"Brandt","sequence":"first","affiliation":[{"name":"School of 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