Neuropharmacology
January 1, 2019
Adam L Halberstadt, Muhammad Chatha, Alexander Stratford et al.
25 citations
Rigid analogs of phenylalkylamine hallucinogens, such as 2C-B-FLY and Bromo-DragonFLY (DOB-DFLY), have emerged as recreational drugs. In mice, the head twitch response—a behavior mediated by the 5-HT2A receptor—was used to compare potencies. DOB (ED50 = 0.75 μmol/kg) and 2C-B (ED50 = 2.43 μmol/kg) induced the response. Benzodifurans DOB-DFLY (ED50 = 0.20 μmol/kg) and 2C-B-DFLY (ED50 = 1.07 μmol/kg) showed significantly higher potency than their non-rigid counterparts. Tetrahydrobenzodifurans DOB-FLY (ED50 = 0.67 μmol/kg) and 2C-B-FLY (ED50 = 1.79 μmol/kg) were approximately equipotent. Three novel tetrahydrobenzodifurans were active but had relatively low potency.
Drug Testing and Analysis
May 22, 2021
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
12 citations
Lysergic acid diethylamide (LSD) is a potent psychoactive substance of clinical interest, and its analogs, including N-methyl-N-isopropyl isomer (MIPLA), have appeared on the street market. This report describes analytical methods to differentiate MIPLA from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion distinguished the three isomers on mass spectral grounds alone. Derivatization with BSTFA improved GC separation. LC-Q-MS and in-source collision-induced dissociation differentiated MIPLA and LAMPA based on distinct m/z 239 ion ratios. An alternative LC-MS/MS method improved separation but LSD co-eluted with iso-LSD; comparing ion ratios at m/z 324.2 > 223.2 and 324.2 > 208.2 facilitated differentiation. Two blotters contained 180 and 186 μg MIPLA per blotter.
Drug Testing and Analysis
March 15, 2026
Simon K. Wellenberg, Lea Wagmann, Matthias D. Kroesen et al.
Amino acid prodrugs of MDMA—MDMA-tryptophan, MDMA-lysine, and MDMA-glycine—are cleaved to release MDMA in zebrafish embryos, human liver S9 fraction, and human urine after microdosing, but not in human blood under the tested conditions. MDMA-tryptophan follows a stepwise bioactivation pathway involving hydroxylation and N-dealkylation before amide cleavage, unlike the other prodrugs which convert directly. Known MDMA metabolites also form in zebrafish and liver systems. Unique urine screening targets appear only for MDMA-tryptophan; biomarkers for the other prodrugs are MDMA and its known metabolites. Further studies of human pharmacokinetic profiles are needed.
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.
ACS Chemical Neuroscience
December 2, 2025
Nina Kastner, Núria Nadal‐gratacós, Selina Hemmer et al.
Replacing the 1,3-benzodioxole group in MDMA (ecstasy) with a 1,3-benzoxathiole yields two analogues, SDA and SDMA, that interact with monoamine transporters similarly to MDMA but with key differences. SDA and SDMA inhibit dopamine and norepinephrine transporters more potently than MDMA and act as partial releasers at serotonin and dopamine transporters. Metabolism studies show SDA and SDMA are cleared faster, while MDMA and MDA degrade only weakly. In mice, SDMA does not produce rewarding effects, unlike MDMA, and SDA only shows a preference for the drug-paired compartment at the lowest dose. SDMA shares similar locomotor and hyperthermic profiles with MDMA, whereas SDA induces increased hyperlocomotion and more sustained hyperthermia. SDMA may be a safer candidate for further study.