2-Oxo-3-hydroxy-LSD

vanc 6 2-Oxo-3-hydroxy-LSD.svg skin-invert-image 200px Serotonin receptor modulator None 111295-09-1 10155149 8330657 KU55DR6345 2-Oxy-3-hydroxy-LSD; OH-LSD; O-H-LSD; 2-Oxo-3-OH-LSD; 2-Oxo-3-hydroxy-2,3-dihydro-LSD; 2-Oxo-3-hydroxylysergide; 2-Oxo-3-hydroxylysergic acid diethylamide; N,N-Diethyl-2,3-dihydro-2-oxo-3-hydroxylysergamide; N,N-Diethyl-3-hydroxy-6-methyl-2-oxo-9,10-didehydro-2,3-dihydroergoline-8β-carboxamide (6aR,9R)-N,N-diethyl-5a-hydroxy-7-methyl-5-oxo-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide 20 25 3 3 CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3(C4=C(C2=C1)C=CC=C4NC3=O)O)C 1S/C20H25N3O3/c1-4-23(5-2)18(24)12-9-14-13-7-6-8-15-17(13)20(26,19(25)21-15)10-16(14)22(3)11-12/h6-9,12,16,26H,4-5,10-11H2,1-3H3,(H,21,25)/t12-,16-,20?/m1/s1 YSZSHHCNLVHCNV-VRORWYBRSA-N 2-Oxo-3-hydroxy-LSD, or 2-oxy-3-hydroxy-LSD, also known as O-H-LSD or OH-LSD, as well as more fully as 2-oxo-3-hydroxy-2,3-dihydro-LSD, is a lysergamide and the major metabolite of the psychedelic drug lysergic acid diethylamide (LSD). Nichols DE Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD) ACS Chemical Neuroscience 9 10 2331–2343 October 2018 29461039 10.1021/acschemneuro.8b00043 https://shaunlacob.com/wp-content/uploads/2020/12/DC-LSD.pdf Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A The pharmacology of lysergic acid diethylamide: a review CNS Neuroscience & Therapeutics 14 4 295–314 2008 19040555 6494066 10.1111/j.1755-5949.2008.00059.x Yu AM Indolealkylamines: biotransformations and potential drug-drug interactions The AAPS Journal 10 2 242–253 June 2008 242 18454322 2751378 10.1208/s12248-008-9028-5 Dolder P The Pharmacology of d-Lysergic Acid Diethylamide (LSD) 2017 10.5451/UNIBAS-006786123 University of Basel https://core.ac.uk/download/pdf/154350706.pdf 3-Гидрокси-2-оксо-ЛСД (2-oxo-3-hydroxy-LSD) АИПСИН 10 November 2015 https://aipsin.com/newsubstance/1551/ ru 1 January 2026 LSD is eliminated 13% as O-H-LSD in urine within 24hours and urinary concentrations of O-H-LSD are 4 to 40times those of LSD in humans. Hintzen A, Passie T The Pharmacology of LSD 29 10 June 2010 OUP/Beckley Foundation Press 978-0-19-958982-1 https://books.google.com/books?id=KTyC-e7NmI8C&pg=PA29 Fig. 2.7 Metabolites of LSD. [...] Meyer MR, Maurer HH Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse Pharmacogenomics 12 2 215–233 February 2011 21332315 10.2217/pgs.10.171 It is rapidly metabolized to the following five metabolites which have been identified in urine or blood from human users: N-demethyl-LSD (nor-LSD), 2-oxo-LSD, 2-oxo-3-hydroxy-LSD, 13-hydroxyLSD and 14-hydroxy-LSD [187–189]. The 13- and 14-hydroxy metabolites are additionally excreted as glucuronides [188]. However, 2-oxo-LSD may be an intermediate in the formation of 2-oxo-3-hydroxy-LSD. Following the incubation of LSD with HLM and hepatocytes, 2,3-dihydroxy-LSD could be identified [190]. 2-oxo-3-hydroxy-LSD was shown to be the main human urinary metabolite with concentrations four- to 40-times higher than that of LSD [187,188,191]. As concluded by Yu in his review on indolalkylamines, almost nothing is known regarding the contribution of specific drug-metabolizing enzymes to the production of individual LSD metabolites in humans. Meyer MR, Maurer HH Drugs of Abuse (Including Designer Drugs) Metabolism of Drugs and Other Xenobiotics 429–463 18 April 2012 10.1002/9783527630905.ch16 Wiley 978-3-527-32903-8 It is metabolized to the following five metabolites: N-demethyl-LSD (nor-LSD), 2-oxo-LSD, 2-oxo-3-hydroxy-LSD, 13-hydroxy-LSD, and 14-hydroxy-LSD [72–74]. The 13- and 14-hydroxy metabolites are additionally excreted as glucuronides [74]. 2-Oxo-3-hydroxy-LSD was shown to be the main human urinary metabolite with concentrations 4–40 times higher than that of LSD [73–75]. In incubations of LSD with human liver microsomes and hepatocytes, 2,3-dihydroxy-LSD could be identified [71]. So far, the contribution and importance of specific enzymes in the formation of the LSD main metabolites such as 2-oxo-3-hydroxy-LSD still remains unclear. The specific enzymes responsible for the formation of O-H-LSD from LSD are unclear. However, subsequent research found involvement of several cytochrome P450 enzymes. Luethi D, Hoener MC, Krähenbühl S, Liechti ME, Duthaler U Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use Biochemical Pharmacology 164 129–138 June 2019 30981875 10.1016/j.bcp.2019.04.013 O-H-LSD is thought to form from other LSD metabolites like 2-oxo-LSD and 3-hydroxy-LSD. Hintzen A, Passie T The Pharmacology of LSD 29 10 June 2010 OUP/Beckley Foundation Press 978-0-19-958982-1 https://books.google.com/books?id=KTyC-e7NmI8C&pg=PA29 Fig. 2.7 Metabolites of LSD. [...] Libânio Osório Marta RF Metabolism of lysergic acid diethylamide (LSD): an update Drug Metabolism Reviews 51 3 378–387 August 2019 31266388 10.1080/03602532.2019.1638931 In vitro studies using liver microsomes and human cryopreserved hepatocytes showed that O-HLSD is a product of LSD biotransformation whose amount increases in a time-dependent manner. In the same study was detected another metabolite in a time-dependent manner upon incubation, the dihydroxy-LSD (Klette et al. 2000). Therefore, LSD is oxidized to 2-oxo-LSD, which undergoes subsequent hydroxylation to O-H-LSD. Although the formation of O-H-LSD may occur via intermediate metabolite dihydroxy-LSD (Figure 1) (Klette et al. 2002). It is unknown whether O-H-LSD is pharmacologically active or produces hallucinogenic effects. Dolder PC, Schmid Y, Haschke M, Rentsch KM, Liechti ME Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans The International Journal of Neuropsychopharmacology 19 1 pyv072 June 2015 26108222 4772267 10.1093/ijnp/pyv072 In the present study, 13% of the orally administered LSD was recovered from urine as O-H-LSD within 24 hours. LSD is metabolized to O-H-LSD by cytochrome P450 enzymes, but the specific enzymes and mechanisms are unknown (Klette et al., 2000). To our knowledge, it is unknown whether O-H-LSD is pharmacologically active. However, O-H-LSD showed profoundly reduced albeit still detectable activity at the serotonin 5-HT2 receptors, including the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, compared to LSD in vitro. O-H-LSD was first described in the scientific literature by at least the 1990s. Vu-Duc T, Vernay A, Calanca A Détection de l'acide lysergique diéthylamide (LSD) dans l'urine humaine: élimination, dépistage et confirmation analytique Schweizerische Medizinische Wochenschrift 121 50 1887–1890 December 1991 1759150 Detection of lysergic acid diethylamide in human urine: elimination, screening and analytical confirmation French Li Z, Goc-Szkutnicka K, McNally AJ, Pilcher I, Polakowski S, Vitone S, Wu RS, Salamone SJ New synthesis and characterization of (+)-lysergic acid diethylamide (LSD) derivatives and the development of a microparticle-based immunoassay for the detection of LSD and its metabolites Bioconjugate Chemistry 8 6 896–905 1997 9404664 10.1021/bc9700594 It started being sold online as an analytical standard by 2024. See also Substituted lysergamide 2-Oxo-LSD 2,3-Dihydro-LSD Nor-LSD Lysergic acid ethyl-2-hydroxyethylamide (LEO) Lysergic acid ethylamide (LAE) 13-Hydroxy-LSD 14-Hydroxy-LSD References External links OH-LSD - Isomer Design Category:Cyclic ketones Category:Diethylamides Category:Hydroxyarenes Category:Lysergamides Category:Psychedelic drug metabolites Category:Serotonin receptor modulators