53 results for "hydroxylation"
Bioactivation and Metabolism of Amino Acid MDMA Prodrugs in Zebrafish Embryos, Human Liver S9, Whole Blood, and Microdosed Human Urine
Drug Testing and Analysis – March 15, 2026
Summary
MDMA prodrugs, specifically MDMA-tryptophan, MDMA-lysine, and MDMA-glycine, were effectively converted to MDMA in zebrafish embryos and human liver samples. In a study involving zebrafish and pooled human liver fractions, 100% of the prodrugs were cleaved to MDMA, with unique metabolites identified for MDMA-tryptophan. Notably, no metabolites appeared in fresh human blood samples, indicating distinct metabolic pathways. This highlights the potential for amino acid prodrugs in controlled drug exposure and emphasizes the need for further investigation into their pharmacokinetics in humans.
Abstract
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA) remains unapproved for therapeutic use despite the promising results of MDMA‐assisted psychothera...
In vivo and in vitro toxicokinetics including metabolism, isozyme mapping, and monoamine oxidase inhibition of three (2-aminopropyl)benzo[b]thiophene (APBT) psychedelics.
Toxicology – March 01, 2026
Summary
New psychoactive substances like 5-APBT and 6-APBT strongly inhibit MAO-A (IC50s 0.4 µM and 0.6 µM), signaling potential serious drug interactions. Their toxicokinetics and metabolism were characterized using LC-HRMS/MS in male Wistar rats (2 mg/kg dose) and human liver models. While metabolism involved multiple enzymes, potentially reducing some toxicity risks, the potent MAO inhibition is a critical finding. This provides vital data for understanding human health impacts and interpreting exposures to these compounds.
Abstract
3-(2-Aminopropyl)benzo[b]thiophene (3-APBT), 5-APBT, and 6-APBT are recently identified psychedelics and entactogens that activate serotonin 2 rece...
Psychedelic Drugs Rediscovered-In Silico Study of Potential Fetal Exposure to Analogues of Psychedelic Drugs During Pregnancy.
Molecules (Basel, Switzerland) – January 08, 2026
Summary
A concerning finding reveals most of 250 psychedelic drugs and ketamine analogues readily cross the human placenta. A QSAR model, incorporating drug-likeness and other factors, identified specific atomic contributions: carbonyl and hydroxyl groups enhance placenta permeability, while bulky structures restrict it. The synthetic availability of these compounds makes them attractive for illicit manufacturing, underscoring the urgency for comprehensive pharmacological investigation into their potential effects.
Abstract
A total of 250 known and novel compounds-ketamine and serotonergic psychedelics or their analogues-designed to target depression, addictions and/or...
Metabolic patterns of new psychoactive substances: Methyl-ketamine and 2-oxo-PCE in rats using UHPLC-QTOF analysis.
Forensic science international. Synergy – December 01, 2025
Summary
Subtle molecular differences profoundly shape how bodies process compounds. Using advanced UHPLC-QTOF analysis, researchers explored the metabolism in vivo of two psychoactive substances, Methyl-ketamine and 2-oxo-PCE, in rats. They discovered distinct markers of metabolism: even slight structural variations, like steric hindrance in Methyl-ketamine, guided unique breakdown pathways compared to 2-oxo-PCE. This work clarifies how molecular shape dictates metabolic outcomes, offering valuable insights for future predictions.
Abstract
This study investigated the metabolic profiles of two isomeric psychoactive agents, methyl-ketamine [2-(ortho-tolyl)-2-(methylamino)cyclohexanone] ...
Electrochemical Simulation of 25B-NBOMe Phase I Metabolism and Metabolite Profiling by HPLC-QTOF-MS.
Molecules (Basel, Switzerland) – November 18, 2025
Summary
Electrochemical simulation of xenobiotic metabolism offers a rapid way to identify 25B-NBOMe's phase I metabolites, crucial for forensic toxicology. Utilizing on-line electrochemistry-mass spectrometry (HPLC-Q-TOF-MS), this method generated key hydroxylated and N-desalkylated derivatives. One significant phase I metabolite, O-desmethyl-25B-NBOMe, was confirmed through biological samples analysis from individuals severely intoxicated. While phase II metabolites, such as glucuronides, appeared exclusively in biological specimens, this electrochemical approach is a valuable screening tool for assessing novel psychoactive substance risks.
Abstract
This is the first report on the electrochemical simulation of phase I metabolism of 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]etha...
Structural identification and metabolic profiling of the new psychoactive substance 2-fluoro-2-oxo-PCPr using NMR and LC-QTOF-MS.
Forensic science international – November 10, 2025
Summary
A newly identified psychoactive substance, 2-fluoro-2-oxo-PCPr, was found to exist in two interconverting rotameric forms, a unique molecular characteristic confirmed by GIAO-DFT NMR calculations. Researchers successfully determined its structure and performed comprehensive metabolite profiling in human samples. Key breakdown products were identified in both urine and hair, providing crucial data for detecting and monitoring this emerging substance in forensic and clinical toxicology.
Abstract
Fluorinated analogs of ketamine, such as 2-fluoro-deschloroketamine and its isomers, have recently emerged as dissociative anesthetics that act thr...
In vitro metabolic fate of 1-[3-(trimethylsilyl)propanoyl] lysergic acid diethylamide (1S-LSD), a silicon-containing LSD analog.
Forensic toxicology – July 29, 2025
Summary
A new silicon-containing drug, 1S-LSD, an LSD analog, surprisingly forms Lysergic acid diethylamide (LSD) early in its in vitro metabolism. Researchers aimed to map its metabolic pathway using human liver microsomes. They identified 62 metabolites, proposing a detailed pathway. This successful characterization helps identify markers for 1S-LSD consumption, enhancing understanding of such compounds.
Abstract
A new lysergic acid diethylamide (LSD) analog has recently been identified, 1-[3-(Trimethylsilyl)propanoyl] LSD (1S-LSD), characterized by a silico...
Metabolism study of two phenethylamine - derived new psychoactive substances using in silico, in vivo, and in vitro approaches.
Archives of toxicology – March 10, 2025
Summary
Scientists have discovered key metabolic markers for detecting two emerging recreational drugs, advancing our ability to identify their use in medical and forensic settings. Using a combination of computer modeling, zebrafish studies, and human liver microsomes, researchers mapped how these phenethylamine compounds break down in the body. The findings revealed unique metabolic fingerprints, with 7-11 distinct breakdown products that can now serve as reliable indicators of drug use. This breakthrough enables more accurate and longer-lasting detection methods.
Abstract
New psychoactive substances (NPS) are substances that are not controlled by international drug control conventions but are abused and pose a threat...
Structural insights into tryptamine psychedelics: The role of hydroxyl indole ring site in 5-HT2A receptor activation and psychedelic-like activity.
European journal of medicinal chemistry – January 05, 2025
Summary
The position of chemical groups on psychedelic compounds dramatically influences their effects in the brain. Scientists found that psilocin, the active form of magic mushrooms, works best when its hydroxyl group is in specific positions on its molecular structure. Using advanced simulations, they revealed how this positioning affects binding to the brain's 5-HT2A receptor, explaining why some compounds produce stronger psychedelic-like activity than others.
Abstract
Recent advancements in the study of mushroom-derived tryptamines, particularly psilocybin and its metabolite psilocin, highlight their unique psych...
Characterization of 17 unknown ketamine manufacturing by-product impurities by UHPLC-QTOF-MS.
Drug testing and analysis – August 01, 2024
Summary
Forensic analysis reveals 17 distinct impurities consistently present in seized ketamine, invaluable for profiling drug sources. Using UHPLC-Q-TOF, 150 samples were investigated, characterizing these impurities, each detected in over 10% of samples. All 17 share a deschloroketamine skeleton, differentiated by specific chlorine, hydroxyl, or methyl substitutions. This detailed impurity profiling provides crucial tactical intelligence for law enforcement, enhancing efforts to track illicit ketamine manufacturing and distribution.
Abstract
This study initially reported the selection and characterization of 17 unknown impurities attributed to the manufacture process of ketamine. A tota...
Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities
Biotechnology Progress – June 18, 2024
Summary
Psychedelics like psilocybin and other tryptamines, natural alkaloids with complex biochemistry, offer promise for mental health treatments. Their biosynthesis, a form of chemical synthesis, is being refined for drug studies. This involves understanding enzymes like TrpM and PsiD, crucial for converting tryptophan derivatives. TrpM successfully N-methylates 4-hydroxytryptophan. However, PsiD struggled with N,N-dimethyl-4-hydroxytryptophan, limiting full psilocybin production. This chemistry expands our knowledge of tryptamines, vital for developing new drugs and understanding natural product roles in health, including potential gut microbiota interactions.
Abstract
Abstract N ‐methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N ‐dimethyltryptamine (DMT), are gaining interest...
In Vivo and In Vitro Metabolic Fate and Urinary Detectability of Five Deschloroketamine Derivatives Studied by Means of Hyphenated Mass Spectrometry.
Metabolites – May 08, 2024
Summary
New research reveals how the body processes emerging psychoactive substances derived from ketamine. Scientists tracked the metabolism of five deschloroketamine variants in both living organisms and lab settings. Using advanced mass spectrometry, they identified 39 unique metabolites, providing crucial data for detecting these substances in urine tests.
Abstract
Ketamine derivatives such as deschloroketamine and deschloro-N-ethyl-ketamine show dissociative and psychoactive properties and their abuse as new ...
Structural characterization and comparative analysis of polymorphic forms of psilocin (4-hy-droxy-N,N-di-methyl-tryptamine).
Acta crystallographica. Section E, Crystallographic communications – May 01, 2024
Summary
Scientists have uncovered new details about psilocin, the active compound that gives magic mushrooms their psychedelic effects. Two distinct crystal forms of this molecule exist, each with unique structural arrangements. Using variable-temperature diffraction techniques, researchers revealed how these forms differ in their molecular bonds and shapes. Form II features an interesting self-folding structure, while Form I creates layered patterns. These findings advance our understanding of how polymorphism affects psychedelic compounds.
Abstract
The title compound, C12H16N2O, is a hy-droxy-substituted mono-amine alkaloid, and the primary metabolite of the naturally occurring psychedelic com...
Identification of clerodane diterpene modifying cytochrome P450 (CYP728D26) in Salvia divinorum - en route to psychotropic salvinorin A biosynthesis.
Physiologia plantarum – January 01, 2024
Summary
A unique plant compound, salvinorin A, offers hope for new pain relievers distinct from traditional opioids. Scientists identified a crucial enzyme, CYP728D26, that performs a key modification on a precursor molecule. This breakthrough significantly advances understanding of the compound's biosynthesis, paving the way for bio-manufacturing and developing alternative analgesics.
Abstract
Salvia divinorum is a hallucinogenic plant native to the Oaxaca in Mexico. The active ingredient for psychotropic effects in this plant is salvinor...
N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation.
Xenobiotica; the fate of foreign compounds in biological systems – December 01, 2023
Summary
The psychedelic compound DMT undergoes complex processing in the body through liver enzymes. Scientists discovered that a specific enzyme, CYP2D6, transforms DMT into new oxygen-containing compounds. Using human liver tissue samples, researchers found that this metabolic pathway works alongside the already-known MAO-A system. This finding advances our understanding of how the body processes DMT and may help explain individual differences in responses.
Abstract
N, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of mon...
Elucidation of the mescaline biosynthetic pathway in peyote (Lophophora williamsii).
The Plant journal : for cell and molecular biology – November 01, 2023
Summary
A breakthrough in understanding peyote's mescaline production reveals a near-complete biosynthetic pathway from l-tyrosine to mescaline. Utilizing transcriptomics, scientists identified key enzymes, including a cytochrome P450 and multiple O-methyltransferases, critical for this process. In engineered yeast strains, these enzymes demonstrated specific substrate interactions, confirming their roles in mescaline biosynthesis. Notably, an N-methyltransferase was also discovered, suggesting its potential involvement in producing tetrahydroisoquinoline alkaloids. This research sheds light on the intricate biochemical processes underlying peyote’s psychoactive properties.
Abstract
Peyote (Lophophora williamsii) is an entheogenic and medicinal cactus native to the Chihuahuan desert. The psychoactive and hallucinogenic properti...
Breaking bad buttons: mescaline biosynthesis in peyote
The Plant Journal – October 20, 2023
Summary
Mescaline, derived from the peyote cactus, has been used in Indigenous ceremonies for over 5,800 years and is now being explored for its potential in treating mental health disorders. In a study involving transcriptomics and gene discovery, researchers identified key enzymes responsible for mescaline's biosynthesis in peyote. They confirmed the presence of low mescaline levels alongside intermediates, suggesting the pathway is intact. This work could pave the way for sustainable synthetic production of mescaline, addressing both therapeutic needs and conservation concerns.
Abstract
The small, globular cactus peyote (Lophophora williamsii) is known for its ability to produce mescaline, a phenethylamine protoalkaloid (Figure 1)....
The molecular basis of the antidepressant action of the magic mushroom extract, psilocin.
Biochimica et biophysica acta. Proteins and proteomics – July 01, 2023
Summary
Groundbreaking research reveals how magic mushrooms' active compound, psilocin, fights depression at the molecular level. The compound binds more strongly than serotonin to brain receptors (5-HT2AR), thanks to its unique chemical structure. Using advanced MD simulations, scientists discovered it's the molecule's tertiary amine group that creates this enhanced binding effect, pointing to new possibilities for antidepressant drug design.
Abstract
Magic mushrooms, and their extract psilocybin, are well-known for their psychedelic properties and recreational use. Psilocin, the bio-active form ...
Discovery of β-Arrestin-Biased 25CN-NBOH-Derived 5-HT2A Receptor Agonists.
Journal of medicinal chemistry – September 22, 2022
Summary
Scientists have discovered new compounds that interact with serotonin receptors in a unique way, offering potential insights into how psychedelic medicines work in the brain. By modifying a known psychedelic compound, researchers created molecules that selectively activate specific cellular pathways, particularly favoring β-arrestin over traditional signaling routes. This breakthrough could help develop more targeted treatments for mental health conditions.
Abstract
The serotonin 2A receptor (5-HT2AR) is the mediator of the psychedelic effects of serotonergic psychedelics, which have shown promising results in ...
Structure identification and analysis of the suspected chemical precursor of 2-fluorodeschloroketamine and its decomposition products.
Drug testing and analysis – June 01, 2022
Summary
The precursor to the illicit drug 2-FDCK, 2-fluorodeschlorohydroxylimine, breaks down into two distinct α-hydroxyl ketones. An advanced analytical method, involving GC-MS and NMR, revealed its complete fragmentation and decomposition pathway. In protic solvents, this compound undergoes hydrolysis, forming a carbon cation that yields the two major decomposition products. Precise structural identification of these products and the precursor's breakdown mechanisms provides crucial insights for forensic analysis, even after samples have degraded.
Abstract
In this work, 1-[(2″-fluorophenyl)(methylimino)methyl]cyclopentan-1-ol (2-fluorodeschlorohydroxylimine) was identified as a suspected chemical prec...
Qualitative and Quantitative Analysis of Tryptamines in the Poison of Incilius alvarius (Amphibia: Bufonidae).
Journal of analytical toxicology – May 20, 2022
Summary
The Colorado River toad's venom holds a potent psychoactive, 5-MeO-DMT. Researchers sought to precisely identify and measure all tryptamine compounds in this poison. Utilizing advanced lab techniques on samples from live Arizona toads, they carefully extracted and analyzed components. 5-MeO-DMT was confirmed as the main compound, present in very high concentrations. Crucially, 5-MeO-tryptamine and two new hydroxylated MeO-DMT forms were successfully identified and quantified for the first time, alongside other tryptamines. This detailed chemical profile offers essential data for forensic applications.
Abstract
Rising numbers of psychoactive tryptamine derivatives have become available on the drug market over the last decade, making these naturally occurri...
Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P‐AL‐LAD
Drug Testing and Analysis – May 07, 2022
Summary
A novel psychedelic, 1P-AL-LAD, acts as a prodrug, converting to AL-LAD as its primary metabolite through in vitro human liver microsome chemistry. This metabolism is crucial for its in vivo hallucinogen effects. In animal studies, 1P-AL-LAD induced head twitches with an ED50 of 491 nmol/kg, nearly three times less potent than AL-LAD (174.9 nmol/kg). This pharmacology suggests its stereochemistry allows for metabolism, including hydroxylation, before activating receptors like lysergic acid diethylamide or psilocybin. Fourteen metabolites were observed, highlighting complex drug studies.
Abstract
Abstract Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important too...
Assessment of Bioactivity‐Modulating Pseudo‐Ring Formation in Psilocin and Related Tryptamines
ChemBioChem – April 28, 2022
Summary
Psilocin, a potent psychedelic tryptamine, profoundly alters consciousness, unlike its close chemical cousin bufotenin. This critical difference stems from a unique intramolecular force: a hydrogen bond forming a pseudo-ring in psilocin's specific molecular arrangement. This fundamental chemistry, vital for understanding psychedelics and drug studies, allows a higher number of uncharged psilocin molecules to cross the blood-brain barrier. Such nuances in chemical synthesis and alkaloids' structural chemistry dictate their neurotransmitter receptor influence on behavior. Psilocybin acts as a prodrug for psilocin, highlighting its therapeutic promise.
Abstract
Abstract Psilocybin ( 1 ) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin ( 2 , 4‐hydroxy‐ N , N ‐dimethyltr...
Tentative identification of in vitro metabolites of O‐acetylpsilocin (psilacetin, 4‐AcO‐DMT) by UHPLC‐Q‐Orbitrap MS
Drug Testing and Analysis – March 21, 2022
Summary
The psychedelic tryptamine 4-AcO-DMT undergoes significant drug metabolism, yielding 15 distinct metabolites. Using *in vitro* human liver *microsomes* and advanced liquid *chromatography*-*Orbitrap mass spectrometry*, 12 phase I and 3 phase II *metabolites* were identified. Biotransformations included *hydroxylation*, *demethylation*, and conjugation with *glucuronic acid*. The hydrolysis *metabolite* was most abundant. This detailed *metabolic pathway chemistry* is crucial for *psychedelics and drug studies*, offering a beta-*hydroxylation* *metabolite* as a biomarker for *forensic toxicology and drug analysis*.
Abstract
Abstract 4‐Acetoxy‐ N , N ‐dimethyltryptamine (4‐AcO‐DMT, psilacetin, O ‐acetylpsilocin) is a synthetic tryptamine with psychedelic properties. Psi...
Hallucinogens
OpenAlex – March 11, 2022
Summary
Hallucinogens profoundly alter perception by targeting specific brain chemistry. Classic psychedelics like Lysergic acid diethylamide (LSD), a derivative of lysergic acid, psilocybin, and mescaline, primarily influence serotonin neurotransmitter receptors. This pharmacology reveals their impact on neuroscience and psychology. Dissociative drugs, including Phencyclidine, operate differently, affecting glutamate. Drug studies explore their therapeutic potential, such as for Treatment of Major Depression, alongside risks of misuse. Understanding this diverse chemistry and how these substances influence behavior is vital.
Abstract
This chapter highlights the similarities in chemical structure and physiologic effects of hallucinogens, as well as their metabolism, therapeutic u...
Phenethylamine-derived new psychoactive substances 2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY: Investigations on their metabolic fate including isoenzyme activities and their toxicological detectability in urine screenings.
Drug testing and analysis – October 01, 2019
Summary
Even novel designer drugs, like certain phenethylamine-based compounds, leave distinct metabolic fingerprints that can be successfully traced. Researchers investigated how the body breaks down specific `new psychoactive substances`, identifying 32 metabolites using advanced `lc−hrms/ms` techniques. This detailed `metabolism` mapping helps forensic experts detect these `drugs of abuse` in urine, confirming that standard screening methods are effective for identifying their intake.
Abstract
Psychoactive substances of the 2C-series are phenethylamine-based designer drugs that can induce psychostimulant and hallucinogenic effects. The so...
Metabolic profile determination of 25N-NBOMe in human liver microsomes by liquid chromatography-quadrupole time-of-flight mass spectrometry.
International journal of legal medicine – May 01, 2019
Summary
Novel synthetic substances often pose detection challenges. Researchers successfully investigated the metabolism of 25N-NBOMe, a psychoactive compound, by exposing it to human liver microsomes. Utilizing advanced LC-Q-TOF/MS technology, they identified 14 distinct metabolites formed through various biotransformations. This detailed metabolic profile provides vital data, greatly assisting in developing biomarkers for detecting 25N-NBOMe in biological samples.
Abstract
2-(2,5-Dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl)ethanamine (25N-NBOMe, 2C-N-NBOMe, NBOMe-2C-N) is a novel synthetic psychoactive substance of th...
Investigating the ability of the microbial model Cunninghamella elegans for the metabolism of synthetic tryptamines
Drug Testing and Analysis – November 21, 2018
Summary
Cunninghamella elegans effectively transforms tryptamines, with 63% of known phase I metabolites detected in its metabolism. This study examined four tryptamines, including the well-known N,N-Dimethyltryptamine (DMT), over 72 hours. Utilizing advanced liquid chromatography–mass spectrometry, researchers identified key metabolic pathways such as hydroxylation and demethylation. Notably, C. elegans produced unique metabolites not previously documented. These findings highlight the fungus's potential as a valuable model for studying the biochemistry of both natural and synthetic tryptamines, crucial for understanding their influence on brain disorders and behavior.
Abstract
Abstract Tryptamines can occur naturally in plants, mushrooms, microbes, and amphibians. Synthetic tryptamines are sold as new psychoactive substan...
Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC-MS, LC-MSn , and LC-HR-MS/MS.
Drug testing and analysis – January 01, 2018
Summary
The body extensively transforms new psychoactive substances, making detection challenging. Researchers uncovered the detailed metabolism of three designer tryptamines, identifying numerous breakdown products. Using advanced techniques like LC-MSn and LC-HR-MS/MS, they successfully mapped how cytochrome-P450 enzymes process these compounds through key chemical changes. Crucially, these sophisticated methods proved highly effective in detecting the tryptamines and their metabolites in urine, even at low doses, offering vital tools for forensic and clinical analysis.
Abstract
Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work w...
Study of the in vitro and in vivo metabolism of the tryptamine 5‐MeO‐MiPT using human liver microsomes and real case samples
Drug Testing and Analysis – July 05, 2017
Summary
5‐methoxy‐N‐methyl‐N‐isopropyltryptamine (5‐MeO‐MiPT) intoxication was linked to a case involving a man exhibiting aggressive behavior, highlighting the drug's emerging prevalence in Germany and Switzerland. In urine samples, 5‐MeO‐MiPT concentrations reached 3,380 ng/mL, while blood levels were at 160 ng/mL. Analysis identified seven phase I metabolites, with demethylation and hydroxylation being the most common processes. Notably, four metabolites were detected in blood and seven in urine, suggesting these compounds could serve as key biomarkers for forensic toxicology related to this designer drug.
Abstract
Abstract The synthetic tryptamine 5‐methoxy‐ N ‐methyl‐ N ‐isopropyltryptamine (5‐MeO‐MiPT) has recently been abused as a hallucinogenic drug in Ge...
Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS.
Analytical and bioanalytical chemistry – February 01, 2017
Summary
Identifying new psychoactive substances like 5-F-DALT, 7-Me-DALT, and 5,6-MD-DALT is crucial for toxicology. Researchers explored their metabolism and detectability. Using advanced LC-MS techniques on biological samples, they identified key metabolic pathways. Positive results show reliable screening for these tryptamine derivatives and their metabolites, even at low doses, especially with LC-HR-MS/MS, significantly improving detection capabilities.
Abstract
Derivatives of N,N-diallyltryptamine (DALT) can be classified as new psychoactive substances. Biotransformation and detectability of 5-fluoro-DALT ...
Urinary Excretion Profiles of 2,5-Dimethoxy-4-alkylthiophenethylamine Analogs in Rats.
Biological & pharmaceutical bulletin – January 01, 2016
Summary
Even subtle changes in chemical structure can significantly alter how the body processes substances. Researchers investigated how rats metabolize three related compounds after oral administration. Through advanced analysis of urine samples, they successfully identified the primary breakdown products for each. Notably, every compound exhibited a distinct metabolic pathway, with one forming a unique β-hydroxylated metabolite, while the others yielded different N-acetylated-sulfoxide variations. This work provides crucial insights into how minor structural differences drive varied excretion profiles.
Abstract
The urinary metabolic profiles of three hallucinogenic 2,5-dimethoxy-4-alkylthiophenethylamine analogs: 2,5-dimethoxy-4-ethylthiophenethylamine (2C...
Biotransformation and detectability of the designer drug 2,5-dimethoxy-4-propylphenethylamine (2C-P) studied in urine by GC-MS, LC-MS(n), and LC-high-resolution-MS(n).
Analytical and bioanalytical chemistry – January 01, 2015
Summary
Even novel designer drugs leave clear metabolic fingerprints. Researchers aimed to map how the hallucinogenic drug 2C-P transforms in the body and its detectability. Using advanced techniques, they successfully identified several key metabolic pathways. Crucially, a common dose of 2C-P is reliably detectable in urine using standard screening methods, providing vital evidence for clinical and forensic investigations.
Abstract
2,5-Dimethoxy-4-propylphenethylamine (2C-P) is a hallucinogenic designer drug of the phenethylamine class, the so-called 2Cs, named according to th...
Effects of 3,4‐methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats
British Journal of Pharmacology – October 12, 2013
Summary
MDMA significantly elevates heart rate and blood pressure, with a notable peak heart rate response at lower doses. In a study involving male rats, MDMA (1-20 mg/kg) increased heart rate by 40% and blood pressure by 30%. Its metabolite, HHMA (1-10 mg/kg), was even more potent, increasing heart rate by 50%, while another metabolite, HHA, had a lesser effect. Notably, propranolol effectively blocked the tachycardia induced by both MDMA and HHMA, highlighting their cardiovascular implications in vivo.
Abstract
Background and Purpose The cardiovascular effects produced by 3,4‐methylenedioxymethamphetamine ( MDMA ; ‘ E cstasy’) contribute to its acute toxic...
Gymnopilin K: a new cytotoxic gymnopilin from Gymnopilus spectabilis
The Journal of Antibiotics – December 21, 2011
Summary
A wild Korean mushroom, *Gymnopilus spectabilis*, known for its hallucinogenic properties, shows promising anti-cancer potential. Extracts from 153g of this fungal species, processed via column chromatography, yielded 20g of active material. A 2.3g fraction demonstrated significant cytotoxicity against human tumor cell lines like A549 using a Sulforhodamine B bioassay. Chemical structure analysis revealed a new compound, gymnopilin K (7mg), alongside four others. This highlights the rich biology and phytochemistry of mushrooms for potential applications in traditional medicine.
Abstract
In our continuing search for structurally interesting and bioactive metabolites from Korean wild mushrooms,1–5 we have collected scores of endemic ...
Enzymatic–nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity
Journal of Neuroscience Research – October 01, 2009
Summary
A single dose of MDMA (20 mg/kg) significantly impacts brain chemistry within hours, leading to neurotoxicity. Within 6 hours, antioxidant enzyme activities in the frontal cortex decreased markedly, while ascorbic acid levels surged in the striatum, hippocampus, and frontal cortex. Malonaldehyde levels, a marker of oxidative stress, rose notably in the striatum after 3 and 6 hours. Immunohistochemical analysis revealed strong reactions in key brain areas, indicating severe cellular stress and potential damage from reactive oxygen species following MDMA administration.
Abstract
Abstract 3,4‐Methylenedioxymethamphetamine (MDMA)‐induced neurotoxicity leads to the formation of quinone metabolities and hydroxyl radicals and th...
Disposition of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and its metabolite 4-bromo-2-hydroxy-5-methoxyphenethylamine in rats after subcutaneous administration.
Toxicology letters – April 21, 2008
Summary
The brain readily absorbs the psychedelic compound 2C-B, with concentrations in brain tissue significantly exceeding those in blood for hours. Researchers explored how rats process 2C-B and its metabolite after administration. They found a major metabolite in lung, brain, and liver. 2C-B quickly entered the brain, showing a 1.1-hour half-life and lung retention. The original compound entered the brain far more efficiently than its metabolite. This drug distribution insight is vital for understanding its effects.
Abstract
The psychedelic compound 4-bromo-2,5-dimethoxyphenethylamine (2C-B) has appeared as an agent in drug abuse or overdose cases in humans. The human p...
Studies on the metabolism and toxicological detection of the designer drug 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E) in rat urine using gas chromatographic-mass spectrometric techniques.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences – October 02, 2006
Summary
The body's intricate process for breaking down new designer drugs reveals how they can be traced. Researchers investigated how the designer drug 2C-E is processed in rats, discovering it undergoes several key metabolic changes that create detectable breakdown products. Using advanced analytical techniques, a systematic toxicological analysis successfully identified the drug at common user doses in rat urine. This robust detection method is expected to be highly effective for identifying 2C-E intake in humans.
Abstract
The phenethylamine-derived designer drug 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E) was found to be mainly metabolized in rats by O-demethyla...
New designer drug 4-iodo-2,5-dimethoxy-beta-phenethylamine (2C-I): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric and capillary electrophoretic/mass spectrometric techniques.
Journal of mass spectrometry : JMS – July 01, 2006
Summary
Detecting new designer drugs like 2C-I in the body poses a significant challenge. To address this, researchers investigated how rats metabolize 2C-I and developed a robust detection method. They found the drug is broken down through specific chemical pathways, with metabolites often excreted in conjugated forms. Using advanced analytical techniques, a systematic procedure was successfully established. This method reliably detected 2C-I intake in rat urine at levels mirroring human drug use, offering a promising tool for human toxicology.
Abstract
Studies are described on the metabolism and the toxicological analysis of the phenethylamine-derived designer drug 4-iodo-2,5-dimethoxy-beta-phenet...
Preparation of Monoclonal Antibodies Reactive to a Hallucinogenic Drug, Psilocin
JOURNAL OF HEALTH SCIENCE – January 01, 2004
Summary
A new monoclonal antibody precisely identifies hallucinogenic psilocin, a key alkaloid in "magic mushrooms." Through sophisticated molecular biology and biochemistry, scientists used chemical synthesis to modify psilocin, coupling it to Keyhole limpet hemocyanin. BALB/c mice, immunized five times, produced antibodies, leading to four selected clones. An immunoassay revealed one antibody (BA631) specifically recognized psilocin, but not psilocybin. This chemistry breakthrough offers a robust tool for identifying these psychedelics in drug studies, aiding enforcement efforts against these hallucinogens.
Abstract
The cultivation or trafficking of “Magic mushrooms,” containing hallucinogenic psilocin and psilocybin, has been prohibited by the Narcotics and Ps...
Metabolism of 18-methoxycoronaridine, an ibogaine analog, to 18-hydroxycoronaridine by genetically variable CYP2C19.
Drug metabolism and disposition: the biological fate of chemicals – June 01, 2002
Summary
A promising compound for addiction treatment, 18-methoxycoronaridine, shows potential in reducing cravings for various substances. Research explored how the body processes this compound. Using advanced techniques, scientists discovered that a specific liver enzyme, CYP2C19, is primarily responsible for its drug metabolism into an active form. This highlights individual differences in how people might respond to its therapeutic potential, based on their unique enzyme activity.
Abstract
18-Methoxycoronaridine, a newly developed ibogaine analog, has been reported to decrease the self-administration of morphine, cocaine, ethanol, and...
Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates
Pharmacogenetics – August 01, 2001
Summary
Individuals with the CYP2D6*10 allele, which affects drug metabolism, may need adjusted medication doses. About 75% of Asians carry this variant, leading to significant differences in how drugs are processed. For instance, when comparing intrinsic clearance ratios using dextromethorphan and MDMA, CYP2D6.10 showed a 123-fold difference in clearance for MDMA versus the wild-type CYP2D6.1. This variant also demonstrated altered susceptibility to inhibitors like fluoxetine and paroxetine, suggesting potential risks for toxicity and drug dependence in those with the *10 allele compared to *1.
Abstract
CYP2D6 is involved in the metabolism of several classes of drugs, including tricyclic antidepressants, selective serotonin reuptake inhibitors and ...
Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT
Synapse – January 01, 2001
Summary
MDMA significantly impairs serotonin (5-HT) levels in the brain, leading to behavioral and neurochemical deficits. In a study with rats, ascorbic acid was shown to effectively suppress hydroxyl radical formation during MDMA exposure, preventing a notable 50% reduction in striatal 5-HT content. Additionally, ascorbic acid maintained normal responses to subsequent MDMA injections, unlike control rats. Notably, MDMA treatment reduced antioxidant levels, including vitamin E and ascorbic acid, highlighting oxidative stress's role in neurotoxicity. This suggests potential therapeutic avenues for protecting against MDMA's harmful effects.
Abstract
MDMA-induced 5-HT neurotoxicity has been proposed to involve oxidative stress due to increased formation of hydroxyl radicals. Recently, MDMA-induc...
Determination of ibogaine and 12-hydroxy-ibogamine in plasma by gas chromatography-positive ion chemical ionization-mass spectrometry.
Journal of analytical toxicology – October 01, 1995
Summary
Ibogaine shows promise in treating stimulant and opiate addiction, with a robust analysis method developed for its evaluation. In tests involving three samples, the assay achieved linear standard curves for ibogaine and its active metabolite, 12-hydroxy-ibogamine, over a concentration range of 10-1,000 ng/mL, with high reliability (average r² values of 0.995 and 0.992). The method exhibited low variability (2.9% to 8.8%) at concentrations of 25, 100, and 300 ng/mL, ensuring accurate quantification in human plasma for at least one week.
Abstract
Ibogaine, an indolamine derivative, is currently being investigated as a potential agent in the treatment of stimulant and opiate addiction. We dev...
3,4,5-Trimethoxyphenylacetaldehyde, an Intermediate Metabolite of Mescaline, Is a Substrate for Microsomal Aldehyde Oxygenase in the Mouse Liver.
Biological and Pharmaceutical Bulletin – January 01, 1995
Summary
3,4,5-Trimethoxyphenylacetaldehyde, a metabolite of mescaline, undergoes oxidation to form 3,4,5-trimethoxyphenylacetic acid in mouse hepatic microsomes at a rate of 0.96 nmol/min/nmol P450. This NADPH-dependent reaction is significantly inhibited by compounds like SKF 525-A and disulfiram. The enzyme responsible, CYP2C29, plays a crucial role in this process, with antibody inhibition reducing activity by 35%. Interestingly, the metabolites exhibit much lower pharmacological effects compared to mescaline itself, highlighting their reduced biological activity.
Abstract
3,4,5-Trimethoxyphenylacetaldehyde, an intermediate metabolite of mescaline, was oxidized to 3,4,5-trimethoxyphenylacetic acid by mouse hepatic mic...
Enzymic and chemical demethylenation of (methylenedioxy)amphetamine and (methylenedioxy)methamphetamine by rat brain microsomes
Chemical Research in Toxicology – May 01, 1992
Summary
The metabolism of methylenedioxyamphetamine (MDA) and methylenedioxy-methamphetamine (MDMA) reveals significant insights into their breakdown in rat brain microsomes. Specifically, 2.6 times more catechol was produced using phosphate buffer compared to HEPES buffer. The study identified dihydroxyamphetamine (DHA) and dihydroxymethamphetamine (DHMA) as metabolic products, with cytochrome P450 playing a crucial role in their formation. Notably, the demethylenation process showed no significant stereoselectivity and involved multiple isozymes, highlighting complex interactions in pharmacology and biochemistry relevant for forensic toxicology and drug analysis.
Abstract
The metabolism of (methylenedioxy)amphetamine (MDA) and (methylenedioxy)methamphetamine (MDMA) was examined in microsomal preparations from rat bra...
Biotransformation of Tryptamine in Fruiting Mycelia ofPsilocybe cubensis
Planta Medica – June 01, 1989
Summary
*Psilocybe cubensis* mycelial cultures demonstrate remarkable biotransformation, converting fed tryptamine into psilocin at unprecedented levels—up to 3.3% dry mass in fruit bodies. This Fungal Biology insight, a fascinating botanical discovery, reveals a unique chemical synthesis pathway for this potent alkaloid. While psilocybin content in these mushrooms is modest (0.01-0.2% dry mass), the high psilocin levels, identified through advanced chromatography, are the highest ever documented. This discovery is significant for Psychedelics and Drug Studies, highlighting the intricate Chemistry and Biology involved in fungal alkaloid production and its stereochemistry.
Abstract
Mycelial cultures of PSILOCYBE CUBENSIS, with the ability to form psilocybin and psilocin DE-NOVO, also hydroxylated and methylated fed tryptamine ...
Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe
Journal of Basic Microbiology – January 01, 1989
Summary
Magic mushroom mycelium demonstrates remarkable chemical capabilities. *Psilocybe cubensis* mycelium, known for producing psilocybin, performs a unique biotransformation. It converts added tryptamine derivatives, like N,N-diethyltryptamine, into novel psychedelics. This involves specific hydroxylation, altering the original chemistry. Up to 3.3% 4-hydroxy-N,N-diethyltryptamine and 0.01–0.8% 4-phosphoryloxy-N,N-diethyltryptamine, new alkaloids, were isolated. This biochemistry highlights fungal biology's role in chemical synthesis and drug studies, potentially influencing neurotransmitter receptor influence on behavior. This stereochemistry is a first for fungal directed biosynthesis.
Abstract
Abstract Mycelial cultures of Psilocybe cubensis capable of forming psilocybin and psilocin de novo display a high capacity for hydroxylation of tr...
In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector
Chemical Research in Toxicology – November 01, 1988
Summary
Four distinct biotransformation pathways of MDMA were identified in rats, revealing a complex metabolism involving N-demethylation and O-glucuronidation. Notably, metabolites like 3-hydroxy-4-methoxymethamphetamine and MDA appeared consistently in urine, with hydroxylated forms excreted primarily as conjugates. In brain and liver samples, N-demethyl and 3-O-methyl phenolic amine metabolites were prevalent. The study involved various sample analyses, including 10,000g rat liver and brain supernatants, highlighting the intricate chemistry of MDMA's metabolic processes and its implications for forensic toxicology.
Abstract
Four biotransformation pathways of 3,4-(methylenedioxy)methamphetamine (MDMA) in the rat have been identified: N-demethylation, O-dealkylation, dea...
Steric and Electronic Relationships among Some Hallucinogenic Compounds
Proceedings of the National Academy of Sciences – September 01, 1970
Summary
Hallucinogenic compounds like LSD, indolcalkylamines, and methoxylated amphetamines share key structural features that enhance their psychoactive effects. Analyzing 150 compounds revealed that the aromatic benzene ring and specific nitrogen atoms are crucial for binding to neurotransmitter receptors. The interaction between these compounds and receptors may involve complex formations, influencing behavior. Notably, correlations show that hallucinogenic potency aligns with the energy of molecular orbitals, underscoring the significance of chemical structure in psychedelic activity.
Abstract
Stereochemical considerations and total valence electron calculations suggest congruities among the ostensibly dissimilar hallucinogenic compounds,...