J Neural Transm (Vienna)
September 12, 2009
Nicholas V. Cozzi, Anupama Gopalakrishnan, Lyndsey L. Anderson et al.
144 citations
N,N-dimethyltryptamine (DMT) and related tryptamines inhibit serotonin transport at the serotonin transporter (SERT) and vesicle monoamine transporter (VMAT2) with varying potencies. DMT, MIPT, DPT, and DIPT inhibited serotonin uptake at SERT with Ki values of 4.00, 8.88, 0.594, and 2.32 µM, respectively. At VMAT2, inhibition was weaker, with Ki values of 93, 20, 19, and 19 µM. The tryptamines were poor inhibitors of radioligand binding to these transporters, yielding high binding-to-uptake ratios. This pattern suggests the tryptamines act as transporter substrates rather than uptake blockers, indicating separate substrate and inhibitor binding sites. The transporters may concentrate tryptamines inside neurons for sigma-1 receptor activation and potential release as transmitters.
Journal of Ethnopharmacology
July 15, 2010
Olabode Ogunbodede, Douglas Mccombs, Keeper Trout et al.
54 citations
Mescaline concentrations in stem tissue of 14 taxa/cultivars of Echinopsis (subgenus Trichocereus) ranged from 0.053% to 4.7% by dry weight, spanning two orders of magnitude. Consistent analytical procedures allowed ranking of species and cultivars, all of which contained mescaline. The findings largely support the hypothesis that plants with the highest mescaline concentrations—especially E. pachanoi from Peru—are most associated with documented shamanic use in traditional South American medicine.
Bioorganic & medicinal chemistry letters
February 1, 2016
Nicholas V. Cozzi, Paul F. Daley
24 citations
N,N-Diallyltryptamine (DALT) and its 5-methoxy derivative (5-MeO-DALT) are tryptamines originally synthesized by Alexander Shulgin, with 5-MeO-DALT reported psychoactive at 12-20 mg and DALT showing few effects at 42-80 mg. This study synthesized additional 5-substituted-DALTs and measured their binding affinities at 45 cloned receptors and transporters. Five DALT compounds had affinities of 10-80 nM for serotonin 5-HT1A and 5-HT2B receptors, while DALT itself had 100 nM affinity at 5-HT1A. Affinities at 5-HT2A receptors were weakest (250-730 nM). Five compounds showed 50-400 nM affinity for 5-HT1D, 5-HT6, and 5-HT7 receptors. Binding also occurred at adrenergic, sigma, histamine, and transporter sites. Quantitative structure-affinity relationships revealed correlations with steric, electronic, and hydrophobic parameters, aiding future drug development.
Drug Testing and Analysis
July 1, 2020
Nicholas V. Cozzi, Paul F. Daley
12 citations
A slightly modified Speeter–Anthony synthesis produced DMT hemifumarate with over 99.9% purity, meeting regulatory standards for human intravenous administration. Aluminum hydride generated in situ from lithium aluminum hydride was used for the first time to reduce an intermediate to DMT, and a quench protocol yielded exceptionally pure free base DMT. The final salt was analyzed by multiple techniques including X-ray powder diffraction, NMR, GC–MS, and HPLC. No significant impurities or residual solvents were detected. The work supports planned clinical trials of DMT for major depressive disorder.
Drug Testing and Analysis
January 1, 2012
Simon D. Brandt, Ruchanok Tearavarich, Nicola M. Dempster et al.
10 citations
Thirteen new tryptamine derivatives were synthesized and analyzed to provide reference data for forensic and clinical identification. Using NMR and mass spectrometry, the compounds were characterized and distinguished from each other and from related substances. Key mass spectral fragments were identified, including an iminium ion and indole-related ions at specific mass-to-charge ratios. The work extends earlier research on similar compounds and supplies analytical standards that can help professionals identify these substances before they cause adverse health effects.
Drug Testing and Analysis
December 29, 2010
Ruchanok Tearavarich, Viwat Hahnvajanawong, Nicola M. Dempster et al.
10 citations
Twelve novel 5-ethoxy-N,N-dialkyl-tryptamines and their deuterated counterparts were synthesized using a microwave-accelerated reduction step that took 5 minutes in tetrahydrofuran at 150 °C. The resulting 24 tryptamines were characterized by nuclear magnetic resonance spectroscopy and gas chromatography ion trap mass spectrometry, revealing differential fragmentation of side-chain-related iminium ions. These compounds are intended as internal standards for bioanalytical and pharmacological assays, aiding identification of novel tryptamines from non-traditional sources, and are of immediate value in forensic, research, and public health contexts.
Drug testing and analysis
December 1, 2024
Keeper Trout, Paul F. Daley
5 citations
The powerful psychedelic 2,5-dimethoxy-4-methylamphetamine (DOM, also known as STP) first appeared in 1967, but the full story is often missing details and includes inaccuracies. Alexander Shulgin supplied the material to Owsley Stanley, who then distributed it to the public for free. Shulgin took an immense risk because DOM was Dow Chemical's intellectual property, and discovery could have jeopardized his career. The article explores why Shulgin released the compound to clandestine operators. DOM faded into oblivion before its human pharmacodynamics and pharmacokinetics could be established, but it later contributed to non-clinical molecular neuroscience by elucidating receptor specificity. Mistaken warnings about combining DOM with chlorpromazine led to better non-pharmacological drug crisis response.