Metabolites
July 27, 2020
Andrea E. Steuer, Daria Kaelin, Martina I. Boxler et al.
32 citations
Three psychoactive stimulants—MDMA, amphetamine, and the new psychoactive substance mephedrone—alter blood metabolites in overlapping but distinct ways. Using plasma samples from controlled human administration studies and liquid chromatography-high resolution mass spectrometry, researchers identified changes in metabolites linked to energy metabolism, steroid biosynthesis, and amino acid pathways. Linoleic acid and pregnenolone-sulfate shifted similarly after intake of all three drugs. Mephedrone produced a metabolic profile more like amphetamine than MDMA, particularly in energy metabolism. These findings could guide future targeted studies on pharmacological actions and help identify biomarkers of drug use.
Metabolites
November 12, 2021
Jitka Nykodemová, Anna Šuláková, Petr Palivec et al.
14 citations
The metabolism of the psychoactive compound 2C-B-Fly-NBOMe was investigated using three systems: human liver microsomes, the fungus Cunninghamella elegans, and live rats. Thirty-five phase I and nine phase II metabolites were identified. Major metabolic pathways include hydroxylation, O-demethylation, oxidative debromination, and N-demethoxybenzylation, followed by glucuronidation or N-acetylation. Human liver microsomes produced the most metabolites at highest concentrations. Two poly-hydroxylated metabolites appeared only in rat urine, while the fungus generated dehydrogenated, N-oxygenated, and dibrominated metabolites. These findings clarify how the body processes this substance, aiding understanding of its effects and potential toxicity.
Metabolites
March 31, 2021
Anna Šuláková, Jitka Nykodemová, Petr Palivec et al.
11 citations
N-Benzylphenethylamines, including 25CN-NBOMe, are novel psychedelic substances with limited metabolism data. This study investigated the metabolic profile of 25CN-NBOMe in rats in vivo and in human liver microsomes and Cunninghamella elegans mycelium in vitro. Major metabolic pathways include mono- and bis-O-demethylation, hydroxylation, and combinations, followed by glucuronidation, sulfation, or N-acetylation of primary metabolites. The cyano group was either hydrolyzed to an amide or carboxylic acid or remained unchanged. Differences between species should be considered in metabolism studies of novel substances.
Metabolites
July 29, 2022
Sara Malaca, Marilyn A. Huestis, Leonardo Lattanzio et al.
8 citations
Synthetic tryptamines like 4-AcO-DiPT are increasingly involved in intoxications and fatalities yet remain unregulated in many countries, with little known about how the body processes them. Using human liver cells and high-resolution mass spectrometry, researchers identified six metabolites formed after three hours of incubation. The main transformation was ester hydrolysis to 4-OH-DiPT, followed by glucuronidation, sulfation, N-oxidation, and N-dealkylation. The most abundant second-generation metabolites were 4-OH-iPT-sulfate and 4-OH-DiPT-glucuronide. The authors suggest that 4-OH-DiPT, 4-OH-iPT, and 4-OH-DiPT-N-oxide are the best biomarkers to detect 4-AcO-DiPT consumption.
Metabolites
January 6, 2023
Sara Malaca, Charline Bottinelli, Laurent Fanton et al.
6 citations
α-Methyltryptamine (α-MT) is a hallucinogenic and stimulant drug linked to overdose deaths. To identify biomarkers proving its use, metabolites were analyzed in lab-grown human liver cells and in urine and blood from a fatal overdose case. Nine metabolites formed in liver cells, with eight more in urine and five in blood. Transformations included hydroxylation, sulfation, glucuronidation, and acetylation. The liver cell model matched real samples, confirming its usefulness. Recommended urine biomarkers are α-MT, hydroxy-α-MT glucuronide, and two hydroxy-α-MT sulfates; blood biomarkers are α-MT, two hydroxy-α-MT sulfates, and N-acetyl-α-MT. More studies with varied doses are needed.
Metabolites
May 8, 2024
Fabian Frankenfeld, Lea Wagmann, Anush Abelian et al.
3 citations
Five deschloroketamine derivatives—deschloro-N-cyclopropyl-ketamine, deschloro-N-ethyl-ketamine, deschloro-N-isopropyl-ketamine, deschloro-N-propyl-ketamine, and deschloroketamine—are primarily metabolized through N-dealkylation, hydroxylation, multiple oxidations, and combinations, plus glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected in rat urine after a 2 mg/kg body weight dose, using liquid chromatography high-resolution tandem mass spectrometry and gas chromatography-mass spectrometry. For the LC-HRMS/MS standard urine screening approach, compound-specific metabolites were identified and confirmed in pooled human liver microsomes for all derivatives except deschloro-N-cyclopropyl-ketamine. The GC-MS approach detected only non-specific acetylated N-dealkylation metabolites.
Metabolites
February 14, 2026
Prajwal Punnamraju, Sascha K Manier, Selina Hemmer et al.
A liquid chromatography–high-resolution mass spectrometry workflow was used to investigate the metabolism of two N1-sulfonated N,N-dimethyltryptamine derivatives, which have potential for both therapeutic use and recreational abuse. Zebrafish larvae and pooled human liver S9 fractions revealed key phase I and phase II biotransformations. Untargeted metabolomics showed significant downregulation of L-threonine associated with compound exposure. These findings advance the understanding of tryptamine metabolism and highlight the value of toxicometabolomics for evaluating novel psychoactive substances.