ACS Pharmacology & Translational Science
December 14, 2020
Adam K. Klein, Muhammad Chatha, Lauren J. Laskowski et al.
103 citations
The 5-HT2A receptor is the primary target for psilocybin and other serotonergic hallucinogens. Seventeen tryptamines with 4-hydroxy or 4-acetoxy groups and various N,N-dialkyl substituents were tested. All acted as full or partial agonists at 5-HT2 subtypes, with similar potencies at 5-HT2A and 5-HT2B receptors, though bulkier N-alkyl groups reduced potency at 5-HT2C receptors and increased 5-HT2B efficacy. O-acetylation reduced in vitro 5-HT2A potency by 10- to 20-fold without altering efficacy. All compounds induced head twitches in mice, consistent with LSD-like effects. Acetylation had little effect on head-twitch potency, suggesting O-acetylated tryptamines may act as prodrugs deacetylated in vivo. These derivatives have psilocybin-like properties, supporting their classification as psychedelic drugs.
Journal of Psychopharmacology
February 21, 2019
Adam L. Halberstadt, Muhammad Chatha, Stephen J. Chapman et al.
25 citations
In mice, the hallucinogenic compound mescaline and several of its chemical analogs produce a distinctive head-twitch response that depends on activation of the 5-HT2A receptor. Adding a methyl group to mescaline (making TMA) doubled its potency, and replacing the 4-methoxy group with larger ethoxy or propoxy groups also increased potency for both mescaline and TMA. However, for a different set of isomers (TMA-2 and its analogs), changing the 4-alkoxy group did not alter potency, even though TMA-2 itself was twice as potent as mescaline. These potency patterns in mice closely match known human hallucinogenic data and show that different substitution patterns on the phenyl ring produce distinct structure-activity relationships.
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.
August 1, 2015
Stephen J. Chapman, Arabo A. Avanes
3 citations
Proton nuclear magnetic resonance (1H NMR) spectra were collected for 28 phenylethanamine compounds sold as psychedelics by 15 online vendors in North America and Europe. The samples included 2C and 2C-T series compounds, mescaline analogues, beta-substituted phenylethanamines, and N-substituted variants with NBOMe, NBOH, or NBMD moieties. Spectra for several of these substances had not been previously documented. The work provides a spectroscopic reference to aid identification of these substances.
August 1, 2015
Stephen J. Chapman, Arabo A. Avanes
3 citations
Proton nuclear magnetic resonance (1H NMR) spectra were collected for 28 purported psychedelic phenylethanamines purchased from 15 unregulated internet vendors in North America and Europe. The samples included members of the 2C and 2C-T series, mescaline analogues, β-substituted phenylethanamines, and N-substituted compounds with NBOMe, NBOH, or NBMD moieties. Several of these spectra had not been previously reported. The study provides a reference database of NMR spectra for these substances, enabling comparison and identification of compounds sold on the grey market.