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Forensic Science International Sep 2015DESIGNER: phenethylamines (PEAs) and cathinones have been encountered worldwide. Complete characterization of these substances can be challenging due to their chirality...
Regioisomeric and enantiomeric analyses of 24 designer cathinones and phenethylamines using ultra high performance liquid chromatography and capillary electrophoresis with added cyclodextrins.
DESIGNER: phenethylamines (PEAs) and cathinones have been encountered worldwide. Complete characterization of these substances can be challenging due to their chirality and variably substituted phenyl rings. In this study, 24 PEAs and cathinones were analyzed by ultra high performance liquid chromatography with photo diode array detection (UHPLC-PDA) on a variety of stationary phases, and by capillary electrophoresis on a dynamically coated capillary with PDA detection (CE-PDA). In the UHPLC-PDA study, a BEH Phenyl column resolved 18 of the 24 regioisomers in 8min, with good discrimination of the PEAs. In contrast, capillary zone electrophoresis (CZE) on a dynamically coated capillary partially or baseline resolved only 10 of the 24 regioisomers, but with improved discrimination of mono-substituted cathinones. A second series of CE-PDA experiments using 80mM (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) in the run buffer resolved all 24 regioisomers and all but two sets of enantiomers within 18min. Five illicit samples were successfully analyzed using the described methods.
Topics: Alkaloids; Chromatography, Liquid; Designer Drugs; Electrophoresis, Capillary; Molecular Structure; Phenethylamines; Stereoisomerism
PubMed: 26232847
DOI: 10.1016/j.forsciint.2015.06.026 -
Journal of Chromatographic Science 2008Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equal mass have been reported as drugs of...
Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equal mass have been reported as drugs of abuse in forensic studies in recent years. These compounds are 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxy-N-N-dimethylamphetamine (MDMMA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB). The mass spectra of the regioisomers (4-methoxy-3-methyl and 4-methoxy-2-methyl-phenethylamines) are essentially equivalent to the three compounds reported as drugs of abuse. This project focused on the synthesis, mass spectral characterization, and chromatographic analysis of these six regioisomeric methoxy methyl phenethylamines. Additionally, the mass spectral and chromatographic properties of these compounds will be compared to the isobaric 2,3- and 3,4-methylenedioxyphenethyl-amines of the same side chain. The six regioisomeric methoxy-methyl-phenethylamines were synthesized from commercially available starting materials. Side chain differentiation by mass spectrometry was possible after the formation of the perfluoroacyl derivatives, pentafluoropropionylamides (PFPA) and heptafluorobutrylamides (HFBA). Gas chromatographic separation on Rtx-1 was successful at resolving the perfluoroacyl derivatives of the 4-methoxy-3-methyl phenethylamines from those of the 4-methoxy-2-methyl phenethylamines. The 4-methoxy-3-methyl-phenethylamine derivatives eluted before the 4-methoxy-2-methyl-phenethylamine derivatives as both the PFPA and HFBA derivatives.
Topics: 3,4-Methylenedioxyamphetamine; Gas Chromatography-Mass Spectrometry; Molecular Structure; Phenethylamines; Stereoisomerism
PubMed: 19007498
DOI: 10.1093/chromsci/46.10.900 -
The Plant Journal : For Cell and... Nov 2023Peyote (Lophophora williamsii) is an entheogenic and medicinal cactus native to the Chihuahuan desert. The psychoactive and hallucinogenic properties of peyote are...
Peyote (Lophophora williamsii) is an entheogenic and medicinal cactus native to the Chihuahuan desert. The psychoactive and hallucinogenic properties of peyote are principally attributed to the phenethylamine derivative mescaline. Despite the isolation of mescaline from peyote over 120 years ago, the biosynthetic pathway in the plant has remained undiscovered. Here, we use a transcriptomics and homology-guided gene discovery strategy to elucidate a near-complete biosynthetic pathway from l-tyrosine to mescaline. We identified a cytochrome P450 that catalyzes the 3-hydroxylation of l-tyrosine to l-DOPA, a tyrosine/DOPA decarboxylase yielding dopamine, and four substrate-specific and regiospecific substituted phenethylamine O-methyltransferases. Biochemical assays with recombinant enzymes or functional analyses performed by feeding putative precursors to engineered yeast (Saccharomyces cerevisiae) strains expressing candidate peyote biosynthetic genes were used to determine substrate specificity, which served as the basis for pathway elucidation. Additionally, an N-methyltransferase displaying broad substrate specificity and leading to the production of N-methylated phenethylamine derivatives was identified, which could also function as an early step in the biosynthesis of tetrahydroisoquinoline alkaloids in peyote.
Topics: Mescaline; Biosynthetic Pathways; Phenethylamines; Tyrosine; Methyltransferases; Cactaceae
PubMed: 37675639
DOI: 10.1111/tpj.16447 -
European Journal of Nuclear Medicine... Apr 2011Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in...
PURPOSE
Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer. In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig brain.
METHODS
Each radiotracer was injected intravenously into anaesthetized Danish Landrace pigs, and the pigs were subsequently scanned for 90 min in a high-resolution research tomography scanner. To evaluate 5-HT(2A) receptor binding, cortical nondisplaceable binding potentials (BP(ND)) were calculated using the simplified reference tissue model with the cerebellum as a reference region.
RESULTS
After intravenous injection, all compounds entered the brain and distributed preferentially into the cortical areas, in accordance with the known 5-HT(2A) receptor distribution. The largest target-to-background binding ratio was found for [(11)C]Cimbi-36 which also had a high brain uptake compared to its analogues. The cortical binding of [(11)C]Cimbi-36 was decreased by pretreatment with ketanserin, supporting 5-HT(2A) receptor selectivity in vivo. [(11)C]Cimbi-82 and [(11)C]Cimbi-21 showed lower cortical BP(ND), while [(11)C]Cimbi-27, [(11)C]Cimbi-29, [(11)C]Cimbi-31 and [(11)C]Cimbi-88 gave rise to cortical BP(ND) similar to that of [(11)C]Cimbi-5.
CONCLUSION
[(11)C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT(2A) receptor agonist binding in the living human brain with PET.
Topics: Animals; Benzylamines; Biological Transport; Brain; Carbon Radioisotopes; Female; Humans; Hydrolysis; Injections, Intravenous; Ketanserin; Phenethylamines; Phosphatidylinositols; Positron-Emission Tomography; Radioactive Tracers; Radiochemistry; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Agonists; Swine
PubMed: 21174090
DOI: 10.1007/s00259-010-1686-8 -
Journal of Animal Science Feb 1993N-methyl-beta-phenethylamine (NMPEA) has been previously identified as the toxin causing locomotor ataxia in sheep and goats grazing the browse plant, Acacia...
N-methyl-beta-phenethylamine (NMPEA) has been previously identified as the toxin causing locomotor ataxia in sheep and goats grazing the browse plant, Acacia berlandieri. We describe a simplified procedure for extraction and quantification of naturally occurring beta-phenethylamines from this Acacia species. Dried, ground plant tissue was extracted (1:20 wt/vol) with 1% glacial acetic acid and filtered. The filtrate was passed through a high-sulfonated polymeric solid-phase extraction (SPE) tube, which retained the compounds of interest (tyramine, hordenine, NMPEA) but allowed many impurities co-extracted from the plant tissue to be washed through. Amines were eluted from the tube, then separated and detected by reversed-phase HPLC. Extracted amines were resolved by HPLC in < 15 min, and UV-absorbance spectra matched those of authentic standards. Recovery efficiency of amine standards (125 micrograms/mL) from SPE tubes averaged 97, 101, and 98% for tyramine, hordenine, and NMPEA, respectively. Excess sample loss was prevented and the large volumes of solvents required for liquid-liquid extraction eliminated by use of solid-phase extraction techniques.
Topics: Acacia; Chromatography, High Pressure Liquid; Phenethylamines
PubMed: 8440668
DOI: 10.2527/1993.712467x -
Pharmacy World & Science : PWS Apr 2004To collect data related to phenethylamine drugs-of-abuse of the 2C-series, to review possible health risks of their use and to discuss legal counter actions of... (Review)
Review
OBJECTIVE
To collect data related to phenethylamine drugs-of-abuse of the 2C-series, to review possible health risks of their use and to discuss legal counter actions of authorities in the European Union (EU).
SETTINGS
Dutch smartshops.
METHODS
In the period of 1994-2002, all products that were claimed to contain synthetic drugs and sold in the smartshops, were purchased. The contents were analysed using analytical chemical technologies such as gas chromatography/mass spectrometry and nuclear magnetic resonance. Additionally, using computerised searches in relevant databases and checking cross-references, literature and documents were screened for scientific based information.
RESULTS
All purchased products proved to be tablets, of which most of them contained one of the phenethylamine designer drugs 2C-B, 2C-T-2 or 2C-T-7. The different drugs were introduced on the Dutch smartshop market within time intervals of approximately three years. The information that was supplied on leaflets and accompanied the products sometimes appeared to be extensive, but was partly misleading and incorrect. Besides that, scientific based information in respect to health risks of drugs of the 2C-series and the detection of their abuse was scarce. Until now no intoxications have been reported in the EU and no centralised legal actions have been taken to prevent possible intoxications.
CONCLUSIONS
The lack of observed intoxications may justify the absence of legal actions in the EU against phenethylamine designer drugs-of-abuse of the 2C-series. However, this may also be explained by either the inability of toxicologists to detect the abuse of substances of the 2C-series or the unawareness of the phenomenon of these drugs. Therefore, EU authorities should promote the availability of relevant standards, validated assays and scientific knowledge regarding these drugs.
Topics: Designer Drugs; Drug Labeling; Enzyme Multiplied Immunoassay Technique; Gas Chromatography-Mass Spectrometry; Illicit Drugs; Magnetic Resonance Spectroscopy; Methamphetamine; Netherlands; Phenethylamines; Psychotropic Drugs; Structure-Activity Relationship
PubMed: 15085947
DOI: 10.1023/b:phar.0000018600.03664.36 -
Neuroscience Bulletin Oct 2013While the cause of dopaminergic neuronal cell death in Parkinson's disease (PD) is not yet understood, many endogenous molecules have been implicated in its... (Review)
Review
While the cause of dopaminergic neuronal cell death in Parkinson's disease (PD) is not yet understood, many endogenous molecules have been implicated in its pathogenesis. β-phenethylamine (β-PEA), a component of various food items including chocolate and wine, is an endogenous molecule produced from phenylalanine in the brain. It has been reported recently that long-term administration of β-PEA in rodents causes neurochemical and behavioral alterations similar to that produced by parkinsonian neurotoxins. The toxicity of β-PEA has been linked to the production of hydroxyl radical ((·)OH) and the generation of oxidative stress in dopaminergic areas of the brain, and this may be mediated by inhibition of mitochondrial complex-I. Another significant observation is that administration of β-PEA to rodents reduces striatal dopamine content and induces movement disorders similar to those of parkinsonian rodents. However, no reports are available on the extent of dopaminergic neuronal cell death after administration of β-PEA. Based on the literature, we set out to establish β-PEA as an endogenous molecule that potentially contributes to the progressive development of PD. The sequence of molecular events that could be responsible for dopaminergic neuronal cell death in PD by consumption of β-PEA-containing foods is proposed here. Thus, long-term over-consumption of food items containing β-PEA could be a neurological risk factor having significant pathological consequences.
Topics: Animals; Cacao; Dopaminergic Neurons; Humans; Nerve Degeneration; Oxidative Stress; Parkinson Disease; Phenethylamines; Wine
PubMed: 23575894
DOI: 10.1007/s12264-013-1330-2 -
Natural Product Reports Aug 1997
Review
Topics: Alkaloids; Animals; Humans; Isoquinolines; Phenethylamines; Psychotropic Drugs
PubMed: 9281839
DOI: 10.1039/np9971400387 -
Natural Product Reports Apr 2001
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Pharmazie in Unserer Zeit Nov 2011
Review
Topics: Adrenergic alpha-2 Receptor Agonists; Epinephrine; Humans; Hypertension; Imidazoles; Phenethylamines; Receptors, Adrenergic, alpha-1
PubMed: 22028135
DOI: 10.1002/pauz.201100446