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Journal of Chromatography. B,... Oct 2008To avoid the spreading of illegal drugs, a designated drug regulation system was introduced along with revision of the Pharmaceutical Affairs Law in Japan in 2006, and...
To avoid the spreading of illegal drugs, a designated drug regulation system was introduced along with revision of the Pharmaceutical Affairs Law in Japan in 2006, and 32 substances including phenethylamine-type drugs were listed in April 2007. In this study, a new simultaneous determination method, based on ultra-fast liquid chromatography coupled with fluorescence detection (UFLC-FL), was developed for the 11 designated phenethylamine drugs. The phenethylamines were labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) at 60 degrees C for 2h in 0.1M borax (pH 9.3). The resulting 11 fluorophores were completely separated by reversed-phase chromatography using an ACQUITY UPLC BEH C(18) column (2.1 mm x 100 mm 1.7 microm) and fluorometrically detected at 550 nm (excitation at 450 nm). The calibration curves obtained from the peak areas versus the injection amounts of the phenethylamines showed a good linearity. The limits of detection (signal-to-noise ratio of 3: S/N=3) on the chromatogram were in the range from 10 fmol (PMMA) to 2.5pmol (MMDA-2). Good accuracy (%) and precision (CV) by intra-day assay and inter-day assay were also obtained using the present procedure. The method was applied to the qualitative and quantitative analyses of phenethylamine in real products obtained from the Japanese market. As the results, BDB (0.24 mg/mg), MMDA-2 (0.98 mg/mL) and 2C-I (0.016 mg/mg) were identified from the different products (powder, liquid and mushroom like). Because the procedure is simple, selective and sensitive, the present method seems to be useful for the qualitative and quantitative analyses of the designated phenethylamines in various samples including biological specimens.
Topics: Chromatography, High Pressure Liquid; Phenethylamines; Sensitivity and Specificity; Substance Abuse Detection
PubMed: 18789774
DOI: 10.1016/j.jchromb.2008.08.020 -
Progress in Drug Research. Fortschritte... 1998The sympathomimetic psychomotor stimulants, including cocaine, amphetamines, and the phenylethylamine amphetamine-like derivatives, exert actions in mammalian systems... (Review)
Review
The sympathomimetic psychomotor stimulants, including cocaine, amphetamines, and the phenylethylamine amphetamine-like derivatives, exert actions in mammalian systems that implicate involvement of the excitatory neurotransmitter, glutamate and its receptors. Despite evidence that psychomotor stimulants do not directly stimulate glutamate receptors, blockade of acute lethal, convulsive, circulatory, thermoregulatory, locomotor and stereotypical responses, as well as interference with slowly developing behavioral sensitization and brain monoaminergic neurotoxicities, can be achieved by receptor antagonists at both N-methyl-D-aspartate and AMPA/kainate glutamate receptor subtypes. Alterations in glutamatergic neurobiology, including elevations in extracellular glutamate levels, changes in glutamate receptor properties and glutamatergic neuronal degeneration, have also been attributed to psychomotor stimulant administration. Blockade of glutamate receptors offers therapeutic options in management of psychomotor stimulant toxicity.
Topics: Animals; Brain; Central Nervous System Stimulants; Cocaine; Glutamic Acid; Humans; Motor Activity; Phenethylamines; Psychomotor Performance; Sympathomimetics
PubMed: 9670779
DOI: 10.1007/978-3-0348-8833-2_4 -
Psychopharmacology Nov 2022Synthetic phenethylamine (PEA) analogs, such as β-methylphenethylamine (BMPEA) and N,α-diethylphenethylamine (DEPEA), are often found in dietary supplements, despite...
RATIONALE
Synthetic phenethylamine (PEA) analogs, such as β-methylphenethylamine (BMPEA) and N,α-diethylphenethylamine (DEPEA), are often found in dietary supplements, despite regulations prohibiting their sale. PEA analogs are structurally related to amphetamine, and we have shown that BMPEA and DEPEA produce cardiovascular stimulation mimicking the effects of amphetamine. However, few studies have examined behavioral effects of BMPEA, DEPEA, and other PEA analogs.
OBJECTIVES
Here, we examined the reinforcing effects of α-ethylphenethylamine (AEPEA, 1 mg/kg/injection), DEPEA (1 mg/kg/injection), and BMPEA (3 mg/kg/injection) as compared to amphetamine (0.1 mg/kg/injection) using a fixed-ratio 1 self-administration paradigm in male rats.
METHODS
Male rats were trained in self-administration chambers containing 2 nose-poke holes. A nose-poke response in the active hole delivered drug or saline, whereas a nose-poke response in the inactive hole had no programmed consequence. Four groups of rats were initially trained for 10 days with the doses noted above. Upon acquisition of drug self-administration, a dose-effect function was determined by training rats on 3 additional doses for 3 days each. A separate group of rats was trained with saline.
RESULTS
Male rats self-administered each PEA analog and amphetamine, as shown by significant increases in active responses versus inactive responses. Subsequent dose-response testing showed clear differences in potency of the compounds. Amphetamine showed a typical inverted U-shaped dose-effect function, peaking at 0.1 mg/kg/injection. AEPEA and DEPEA also showed inverted dose-effect functions, with each peaking at 0.3 mg/kg/injection. BMPEA did not show an inverted U-shaped dose-effect function, but active responding slowly increased up to a dose of 6 mg/kg/injection.
CONCLUSIONS
Taken together, our findings indicate that dietary supplements containing PEA analogs may have significant abuse liability when used recreationally.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Amphetamine; Phenethylamines; Self Administration; Dietary Supplements; Dose-Response Relationship, Drug
PubMed: 36190536
DOI: 10.1007/s00213-022-06246-x -
European Journal of Pharmacology Sep 2019Preworkout supplements ("boosters") are used to enhance physical and mental performance during workouts. These products may contain various chemical substances with...
Preworkout supplements ("boosters") are used to enhance physical and mental performance during workouts. These products may contain various chemical substances with undefined pharmacological activity. We investigated whether substances that are contained in commercially available athletic multiple-ingredient preworkout supplements exert amphetamine-type activity at norepinephrine, dopamine, and serotonin transporters (NET, DAT, and SERT, respectively). We assessed the in vitro monoamine transporter inhibition potencies of the substances using human embryonic kidney 293 cells that expressed the human NET, DAT, and SERT. The phenethylamines β-phenethylamine, N-methylphenethylamine, β-methylphenethylamine, N-benzylphenethylamine, N-methyl-β-methylphenethylamine, and methylsynephrine inhibited the NET and less potently the DAT similarly to D-amphetamine. β-phenethylamine was the most potent, with IC values of 0.05 and 1.8 μM at the NET and DAT, respectively. These IC values were comparable to D-amphetamine (IC = 0.09 and 1.3 μM, respectively). The alkylamines 1,3-dimethylbutylamine and 1,3-dimethylamylamine blocked the NET but not the DAT. Most of the phenethylamines interacted with trace amine-associated receptor 1, serotonin 5-hydroxytryptamine-1A receptor, and adrenergic α and α receptors at submicromolar concentrations. None of the compounds blocked the SERT. In conclusion, products that are used by athletes may contain substances with mainly noradrenergic amphetamine-type properties.
Topics: Biogenic Monoamines; Biological Transport; Catecholamine Plasma Membrane Transport Proteins; Dietary Supplements; Exercise; HEK293 Cells; Humans; Performance-Enhancing Substances; Phenethylamines
PubMed: 31265842
DOI: 10.1016/j.ejphar.2019.172515 -
Nature Aug 2017Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and...
Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and 'pharmacoterrorism' in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system. Although the psychoactive properties of fenethylline have been reported to differ from those of other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects. Here we develop a 'dissection through vaccination' approach, called DISSECTIV, to mitigate the psychoactive effects of fenethylline and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against a single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacological activity. We anticipate that DISSECTIV will be used to expose unidentified active chemical species and resolve pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples and natural product extracts.
Topics: Amphetamine; Amphetamines; Animals; Biological Products; Central Nervous System Stimulants; Chemical Fractionation; Cytochrome P-450 Enzyme System; Drug Synergism; Haptens; Hemocyanins; Illicit Drugs; Male; Mice; Phenethylamines; Theophylline; Vaccines
PubMed: 28813419
DOI: 10.1038/nature23464 -
ACS Chemical Neuroscience Jul 2022Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory...
Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory rodents, the zebrafish () is a powerful animal model organism for screening neuroactive drugs, including hallucinogens. Here, we test a battery of ten novel -benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -OCH, -OCF, -F, -Cl, and -Br substitutions in the position of the phenyl ring of the -benzyl moiety, assessing their acute behavioral and neurochemical effects in the adult zebrafish. Overall, substitutions in the Overall, substitutions in the -benzyl moiety modulate locomotion, and substitutions in the phenethylamine moiety alter zebrafish anxiety-like behavior, also affecting the brain serotonin and/or dopamine turnover. The 24H-NBOMe(F) and 34H-NBOMe(F) treatment also reduced zebrafish despair-like behavior. Computational analyses of zebrafish behavioral data by artificial intelligence identified several distinct clusters for these agents, including anxiogenic/hypolocomotor (24H-NBF, 24H-NBOMe, and 34H-NBF), behaviorally inert (34H-NBBr, 34H-NBCl, and 34H-NBOMe), anxiogenic/hallucinogenic-like (24H-NBBr, 24H-NBCl, and 24H-NBOMe(F)), and anxiolytic/hallucinogenic-like (34H-NBOMe(F)) drugs. Our computational analyses also revealed phenotypic similarity of the behavioral activity of some NBPEAs to that of selected conventional serotonergic and antiglutamatergic hallucinogens. functional molecular activity modeling further supported the overlap of the drug targets for NBPEAs tested here and the conventional serotonergic and antiglutamatergic hallucinogens. Overall, these findings suggest potent neuroactive properties of several novel synthetic NBPEAs, detected in a sensitive in vivo vertebrate model system, the zebrafish, raising the possibility of their potential clinical use and abuse.
Topics: Animals; Artificial Intelligence; Behavior, Animal; Hallucinogens; Phenethylamines; Zebrafish
PubMed: 35671176
DOI: 10.1021/acschemneuro.2c00123 -
Biological Psychiatry Jan 1991Urinary excretion (24-hr) of beta-phenylethylamine (PEA), phenylacetic acid (PAA), phenylalanine (Phe), and p-tyrosine (Tyr), and plasma levels of PAA, Phe, and Tyr were...
Urinary excretion (24-hr) of beta-phenylethylamine (PEA), phenylacetic acid (PAA), phenylalanine (Phe), and p-tyrosine (Tyr), and plasma levels of PAA, Phe, and Tyr were examined in 18 normal children and 26 children diagnosed as having attention-deficit hyperactivity disorder (ADHD). The results indicated that urinary excretion (expressed per g of creatinine) of free and total PEA was significantly lower in the ADHD patients, and plasma levels of Phe and Tyr were also decreased in the ADHD subjects compared with the normal controls.
Topics: Attention Deficit Disorder with Hyperactivity; Child; Humans; Phenethylamines; Phenylacetates; Phenylalanine; Reference Values; Tyrosine
PubMed: 2001444
DOI: 10.1016/0006-3223(91)90207-3 -
Applied Spectroscopy Oct 2013We evaluated the normal Raman (NR) and the surface-enhanced Raman scattering (SERS) of three sympathomimetic amines: phenethylamine, ephedrine, and...
We evaluated the normal Raman (NR) and the surface-enhanced Raman scattering (SERS) of three sympathomimetic amines: phenethylamine, ephedrine, and 3,4-methylenedioxymethamphetamine (MDMA). In addition, quantum mechanical calculations-geometry optimization and calculations of the harmonic vibrational frequencies-were performed using the density functional theory (DFT) approach. Vibrational assignments were made by comparing the experimental and calculated spectra. The study found that both NR and SERS provided excellent spectra for the drugs tested. Certain conditions, such as response to various laser wavelengths and background fluorescence of the analyte, could be easily managed using SERS techniques. The DFT-calculated spectra could be correlated with the experimental spectra without the aid of a scaling factor. We also present a set of discriminant bands, useful for distinguishing the three compounds, despite their structural similarities.
Topics: Models, Molecular; Phenethylamines; Sodium Chloride; Spectrum Analysis, Raman
PubMed: 24067571
DOI: 10.1366/13-06990 -
Biomedical Chromatography : BMC Feb 2022The misuse of 2-phenylethylamine (PEA) in sporting competitions is prohibited by the World Anti-Doping Agency. As it is endogenously produced, a method is required to...
The misuse of 2-phenylethylamine (PEA) in sporting competitions is prohibited by the World Anti-Doping Agency. As it is endogenously produced, a method is required to differentiate between naturally elevated levels of PEA and the illicit administration of the drug. In 2015, a sulfo-conjugated metabolite [2-(2-hydroxyphenyl)acetamide sulfate (M1)] was identified, and pilot study data suggested that the ratio M1/PEA could be used as a marker indicating the oral application of PEA. Within this project, the required reference material of M1 was synthesized, single and multiple dose elimination studies were conducted and 369 native urine samples of athletes were analyzed as a reference population. While the oral administration of only 100 mg PEA did not affect urinary PEA concentrations, an increase in urinary concentrations of M1 was observed for all volunteers. However, urinary concentrations of both PEA and M1 showed relatively large inter-individual differences and establishing a cut-off-level for M1/PEA proved difficult. Consequently, a second metabolite, phenylacetylglutamine, was considered. Binary logistic regression demonstrated a significant (P < 0.05) correlation of the urinary M1 and phenylacetylglutamine concentrations with an oral administration of PEA, suggesting that assessing both analytes can assist doping control laboratories in identifying PEA misuse.
Topics: Adult; Biomarkers; Chromatography, Liquid; Doping in Sports; Female; Humans; Limit of Detection; Linear Models; Male; Middle Aged; Phenethylamines; Reproducibility of Results; Substance Abuse Detection; Tandem Mass Spectrometry; Young Adult
PubMed: 34729800
DOI: 10.1002/bmc.5274 -
Nature Sep 1975
Topics: Cacao; Humans; Migraine Disorders; Phenethylamines
PubMed: 1167288
DOI: 10.1038/257256a0