Brandt Simon D, Kavanagh Pierce V, Gare Sarah, Elliott Simon P, Stratford Alexander, Halberstadt Adam L
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
Drug Test Anal. 2024 Dec 3. doi: 10.1002/dta.3829.
The classical psychedelic drug (+)-lysergic acid diethylamide (LSD) continues to attract considerable multidisciplinary interest, and over the last eight decades, many derivatives and analogs of LSD have been synthesized. One site on the ergoline scaffold of LSD that has been frequently modified is the N-position, with the N-acylated LSD derivative 1-acetyl-LSD (1A-LSD, ALD-52) being one of the earliest examples. In more recent years, several other alkylcarbonyl- and cycloalkylcarbonyl-substituted LSD derivatives have been evaluated, including several distributed as research chemicals. Although N-substitution is detrimental for the activity of LSD at the 5-HT receptor (the primary site of action of psychedelic drugs), N-acylated LSD derivatives are rapidly hydrolyzed in vivo and are believed to act as prodrugs for LSD. Recently, 1-(thiophene-2-carbonyl)-LSD (1T-LSD, SYN-L-021) was detected as a new recreational drug, signaling a move towards N-acyl groups with an aromatic character. The present study was conducted to investigate the analytical profile and pharmacology of 1-(2-furoyl)-lysergic acid diethylamide (1F-LSD, SYN-L-005), a novel analog of 1T-LSD. The binding of 1F-LSD to the 5-HT receptor and other monoamine sites was assessed using radioligand binding. Furthermore, the in vivo activities of 1F-LSD and 1T-LSD were assessed in C57BL/6 J mice by comparing their biotransformation to LSD and effects on the head-twitch response (HTR), a 5-HT-mediated behavior. Both 1F-LSD and 1T-LSD induced the HTR in mice and were hydrolyzed to LSD after in vivo administration, indicating that both substances exhibit LSD-like properties and may serve as prodrugs for LSD.
经典致幻药物（+）-麦角酸二乙酰胺（LSD）持续吸引着多学科的广泛关注。在过去的八十年里，人们合成了许多LSD的衍生物和类似物。LSD麦角灵骨架上一个经常被修饰的位点是N位，N-酰化LSD衍生物1-乙酰基-LSD（1A-LSD，ALD-52）就是最早的例子之一。近年来，人们又评估了其他几种烷基羰基和环烷基羰基取代的LSD衍生物，其中一些作为研究用化学品进行了分发。尽管N-取代对LSD在5-羟色胺受体（致幻药物的主要作用位点）上的活性不利，但N-酰化LSD衍生物在体内会迅速水解，被认为是LSD的前体药物。最近，1-（噻吩-2-羰基）-LSD（1T-LSD，SYN-L-021）被检测为一种新型娱乐性药物，这表明人们开始转向具有芳香特性的N-酰基。本研究旨在调查1-（2-糠酰基）-麦角酸二乙酰胺（1F-LSD，SYN-L-005）的分析特征和药理学，它是1T-LSD的一种新型类似物。使用放射性配体结合法评估了1F-LSD与5-羟色胺受体及其他单胺位点的结合情况。此外，通过比较1F-LSD和1T-LSD在C57BL/6 J小鼠体内向LSD的生物转化及其对头部抽搐反应（HTR，一种5-羟色胺介导的行为）的影响，评估了它们的体内活性。1F-LSD和1T-LSD均可在小鼠体内诱导HTR，并在体内给药后水解为LSD，这表明这两种物质均具有LSD样特性，可能是LSD的前体药物。
