Biochemical Pharmacology
September 29, 2011
Andrea E. Schwaninger, Markus R Meyer, Allan J. Barnes et al.
23 citations
The R- and S-enantiomers of MDMA are eliminated differently in human urine. After controlled oral doses of 1.0 and 1.6 mg/kg, urine from ten participants was analyzed. Over five days, a median of 21% of the measured compounds were excreted as R-stereoisomers and 17% as S-stereoisomers. Significantly more R-enantiomers of MDMA, DHMA, and HMMA sulfate were excreted, while more S-stereoisomers of HMMA and HMMA glucuronide were excreted. No significant differences appeared for MDA and DHMA sulfate. The ratio of R- to S-stereoisomers changed steadily over the first 48 hours, suggesting it could help estimate time of MDMA ingestion in clinical and forensic toxicology.
Talanta
October 1, 2018
Achim T. Caspar, Markus R Meyer, Folker Westphal et al.
17 citations
Two new hallucinogens, 3,4-DMA-NBOMe and 4-MMA-NBOMe, are extensively metabolized in rats and human liver preparations. Using nano liquid chromatography with high-resolution mass spectrometry, 38 metabolites of 3,4-DMA-NBOMe and 33 metabolites of 4-MMA-NBOMe were identified. The main metabolic pathways are O-demethylation and glucuronic acid conjugation for 3,4-DMA-NBOMe, and oxidation of the tolyl group to carboxylic acid for 4-MMA-NBOMe. The nanoLC approach performed comparably to conventional UHPLC. Standard urine screening methods could detect an estimated low user dose only through metabolites. Suggested screening targets include O-demethyl- and O,O-bis-demethyl-3,4-DMA-NBOMe and their glucuronides, and carboxy-4-MMA-NBOMe and its glucuronide and N-demethyl-carboxy-4-MMA-NBOMe.
Drug Testing and Analysis
January 1, 2017
Simon D. Brandt, Pierce V. Kavanagh, Geraldine Dowling et al.
16 citations
Many N,N-dialkylated tryptamines have psychoactive properties in humans, and the number of derivatives has grown across research areas. Some are used in medicinal products, others as recreational drugs, and sometimes these uses overlap. 5-Methoxy-N,N-diallyltryptamine (5-MeO-DALT) recently emerged as a new psychoactive substance, while 4-acetoxy-DALT and unsubstituted DALT have been detected only recently. This report describes the analytical characterization of 17 N,N-diallyltryptamines (DALTs), including 15 prepared via microwave-accelerated synthesis. The compounds were characterized using NMR, GC-MS, mass spectrometry, photodiode array detection, and GC solid-state infrared analysis. The resulting spectral data are provided to help researchers identify newly emerging substances and explore clinical and non-clinical uses.
Analytical and Bioanalytical Chemistry
January 1, 2015
Carina S. D. Wink, Markus R Meyer, Tina Braun et al.
13 citations
2C-P is a hallucinogenic designer drug from the phenethylamine class. This work identified its phase I and II metabolites and tested detectability in urine. Proposed metabolic pathways include N-acetylation, deamination with reduction to alcohol or oxidation to carbonic acid, mono- and bis-hydroxylation, mono- and bis-O-demethylation followed by glucuronidation or sulfation, and combinations. A common user's dose of 2C-P was reliably detectable in urine using standard GC-MS and LC-MS(n) screening methods, supporting its identification in clinical and forensic cases.
Analytical and Bioanalytical Chemistry
July 19, 2019
Lea Wagmann, Lilian H. J. Richter, Tobias Kehl et al.
Nine LSD derivatives—ALD-52, 1P-LSD, 1B-LSD, ETH-LAD, 1P-ETH-LAD, AL-LAD, ECPLA, LSZ, and LSM-775—are metabolized in pooled human liver S9 fractions primarily through N-dealkylation and hydroxylation, mainly catalyzed by CYP1A2 and CYP3A4. ALD-52, 1P-LSD, and 1B-LSD undergo deacylation to LSD. Many metabolites are structurally identical, complicating differentiation in urinalysis. However, after administering expected recreational doses to rats, neither parent drugs nor metabolites were detectable in urine using standard screening approaches.
Toxicology Letters
March 15, 2018
Achim T. Caspar, Markus R Meyer, Hans H Maurer
Six NBOMe-derived new psychoactive substances (25B-, 25C-, 25I-, 3,4-DMA-, 4-EA-, and 4-MMA-NBOMe) are metabolized by multiple cytochrome P450 enzymes, primarily CYP2D6 and CYP2C19. Michaelis-Menten kinetic constants were determined using the substrate depletion approach; Km values ranged from 0.010 μM (CYP2D6, 4-MMA-NBOMe) to 13 μM (CYP2B6, 4-EA-NBOMe). CYP2D6 contributed most to hepatic net clearance for five compounds (61–89%), while CYP2C19 dominated for 4-MMA-NBOMe (64%). Because multiple isoforms are involved, the risk of drug-drug interactions may be low, but inter-individual variation in metabolism is possible for substances highly dependent on polymorphic CYP2C19 or CYP2D6.
Toxicology Letters
April 15, 2017
Lea Wagmann, Simon D. Brandt, Pierce V. Kavanagh et al.
Thirteen analogs of the psychoactive substance alpha-methyltryptamine (AMT) were tested for their ability to inhibit monoamine oxidase (MAO), an enzyme that breaks down neurotransmitters. All analogs inhibited MAO-A, with IC50 values ranging from 0.049 to 166 μM, and four also inhibited MAO-B (IC50 82–376 μM). 7-Me-AMT was the most potent MAO-A inhibitor, comparable to the known inhibitors harmine and harmaline, and acted competitively. Most analogs also inhibited MAO in human liver S9 fractions. These findings suggest that MAO inhibition by these compounds could contribute to dangerous serotonin- and adrenaline-related effects, especially when combined with other drugs that block monoamine reuptake.
Toxicology Letters
October 8, 2009
Markus R Meyer, Frank T. Peters, Hans H Maurer
The human liver enzymes CYP2D6 and CYP3A4 are primarily responsible for breaking down the chiral designer drugs MDA and BDB, which are also metabolites of MDMA (Ecstasy) and related compounds. The enzymes preferentially process the S-enantiomer of these substances. This metabolic step, called demethylenation, converts the drugs into catecholamines. The findings help clarify how these substances are cleared from the body and may inform understanding of their effects and toxicity in recreational users.
Biochemical Pharmacology
June 1, 2009
Markus R Meyer, Frank T. Peters, Hans H Maurer
Cytochrome P450 isozymes responsible for metabolizing the designer drug MBDB (Eden) were identified for the first time. The main metabolites produced are DHMBB and BDB. Dealkylation is primarily catalyzed by CYP2B6 and CYP2C19, while demethylenation also involves CYP1A2, CYP2D6, and CYP3A4. After in vitro-in vivo correlation, CYP2D6 is the most abundant isozyme for total MBDB metabolism, and CYP2C19 is the most enantioselective, metabolizing the S-enantiomer at a higher rate at low substrate concentrations. Inhibition studies with quinidine confirmed CYP2D6's dominant role. These findings align with results for similar amphetamines.