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Human Psychopharmacology Jan 2020The number of novel psychedelic phenethylamines and tryptamines has continued to increase, but little academic research has focused on the effects of these substances....
OBJECTIVE
The number of novel psychedelic phenethylamines and tryptamines has continued to increase, but little academic research has focused on the effects of these substances. We sought to determine and compare the subjective effects of various substances.
METHODS
We conducted in-depth interviews with 39 adults (75.4% male and 87.2% White) who reported experience using psychedelic phenethylamines and/or tryptamines. Participants described the effects of compounds they have used. We examined the subjective drug effects in a qualitative descriptive manner.
RESULTS
Participants reported on the use of 36 compounds. The majority (64.1%) reported the use of 2C series drugs, with 2C-B use being most prevalent; 38.5% reported the use of NBOMe, and 25.6% reported the use of DOx. With regard to tryptamines, 46.2% reported use, and 4-AcO-DMT was the most prevalent drug used in this class. 2C-B was often described as being more favorable than other 2C series compounds with the effects described as being comparable with MDMA and LSD. NBOMe effects were generally described in an unfavorable manner, and the effects of DOx were often described as lasting too long (12-36 hr). The effects of 4-AcO-DMT were often described as mimicking psilocybin.
CONCLUSION
Knowing the effects of various compounds can inform education, prevention, and harm reduction efforts regarding the use of these drugs.
Topics: Adolescent; Adult; Drug Users; Female; Hallucinogens; Humans; Male; Phenethylamines; Qualitative Research; Self Report; Tryptamines; Young Adult
PubMed: 31909513
DOI: 10.1002/hup.2719 -
Journal of Animal Science Aug 2022Beta-adrenergic agonists (β-AAs) are widely used supplements in beef and pork production to improve feed efficiency and increase lean muscle mass, yet little is known...
Beta-adrenergic agonists (β-AAs) are widely used supplements in beef and pork production to improve feed efficiency and increase lean muscle mass, yet little is known about the molecular mechanism by which β-AAs achieve this outcome. Our objective was to identify the influence of ractopamine HCl and zilpaterol HCl on mitochondrial respiratory activity in muscle satellite cells isolated from crossbred beef steers (N = 5), crossbred barrows (N = 2), Yorkshire-cross gilts (N = 3), and commercial weather lambs (N = 5). Real-time measurements of oxygen consumption rates (OCRs) were recorded using extracellular flux analyses with a Seahorse XFe24 analyzer. After basal OCR measurements were recorded, zilpaterol HCl, ractopamine HCl, or no β-AA was injected into the assay plate in three technical replicates for each cell isolate. Then, oligomycin, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, and rotenone were injected into the assay plate sequentially, each inducing a different cellular state. This allowed for the measurement of OCR at these states and for the calculation of the following measures of mitochondrial function: basal respiration, non-mitochondrial respiration, maximal respiration, proton leak, adenosine triphosphate (ATP)-linked respiration, and spare respiratory capacity. Incubation of bovine cells with either zilpaterol HCl or ractopamine HCl increased maximal respiration (P = 0.046) and spare respiratory capacity (P = 0.035) compared with non-supplemented counterparts. No difference (P > 0.05) was observed between zilpaterol HCl and ractopamine HCl for maximal respiration and spare respiratory capacity in bovine cell isolates. No measures of mitochondrial function (basal respiration, non-mitochondrial respiration, maximal respiration, proton leak, ATP-linked respiration, and spare respiratory capacity) were altered by β-AA treatment in ovine or porcine cells. These findings indicate that β-AAs in cattle may improve the efficiency of oxidative metabolism in muscle satellite cells by modifying mitochondrial respiratory activity. The lack of response by ovine and porcine cells to β-AA incubation also demonstrates differing physiological responses to β-AA across species, which helps to explain the variation in its effectiveness as a growth supplement.
Topics: Adenosine Triphosphate; Adrenergic beta-Agonists; Animals; Cattle; Female; Myoblasts; Oxidative Phosphorylation; Phenethylamines; Protons; Sheep; Sheep, Domestic; Swine
PubMed: 35908785
DOI: 10.1093/jas/skac208 -
Molecules (Basel, Switzerland) Oct 2020New developments in the synthesis, resolution, and synthetic applications of chiral 1-phenylethylamine (α-PEA) reported in the last decade have been reviewed. In... (Review)
Review
New developments in the synthesis, resolution, and synthetic applications of chiral 1-phenylethylamine (α-PEA) reported in the last decade have been reviewed. In particular, improvements in the synthesis of α-PEA and its derivatives and chiral resolution, as well as their applications in the resolution of other compounds, were discussed. α-PEA was used as a chiral auxiliary in the diastereoselective synthesis of medicinal substances and natural products. Chiral ligands with α-PEA moieties were applied in asymmetric reactions, and effective modular chiral organocatalysts were constructed with α-PEA fragments and used in important synthetic reactions.
Topics: Chemistry Techniques, Synthetic; Phenethylamines; Stereoisomerism
PubMed: 33114098
DOI: 10.3390/molecules25214907 -
Science & Justice : Journal of the... Jul 2019Since the introduction of the European Early Warning System in 2005, >700 new psychoactive substances (NPS) have been listed. This review article presents for the first... (Comparative Study)
Comparative Study Review
Since the introduction of the European Early Warning System in 2005, >700 new psychoactive substances (NPS) have been listed. This review article presents for the first time the Swiss narcotic law in perspective of scheduling of NPS, and compares it to the regulations of the German speaking neighbours Austria and Germany. The Swiss way is a fast and effective way for scheduling NPS, with the purpose to restrict drug trafficking and for controlling the NPS drug market: the legal basis for scheduling substances of abuse is the "Law about narcotics and psychotropic substances" (BetmG, SR 812.121), which includes the "narcotic law directory (BetmVV-EDI, SR 812.121.11) suitable for listing all controlled substances. The BetmVV-EDI, SR 812.121.11 contains seven indices, with index e specifically designed for the fast scheduling of NPS. Newly appearing NPS can either be controlled under a structure analogues definition or by listing single substances. The list of single substances is updated at least once per year, and structure analogues definitions can be implemented, in order to keep track with new developments on the NPS market. The latest version from November 30th 2018 contains ten different structure analogue definitions and 207 single substances. Requirements to list NPS are their appearance on the NPS market, suspected psychotropic effects and their suggestions by Forensic professionals. As soon as substances are newly placed, on Schedule I of the 1961 Convention or Schedule II of the 1971 Convention by the Commission on Narcotic Drugs of the World Health Organization they can easily be transferred from index e to index a-d of the BetmVV-EDI, SR 812.121.11. The Austrian law uses a structure analogue and single substances approach (introduced in 2012, one update in 2016), whereas the German NPS law (established in 2016, no update yet) only lists two structure-analogue-definitions. All three legislations have defined which core structures, kinds and sites of substitutions are regulated.
Topics: Alkaloids; Austria; Cannabinoids; Controlled Substances; Drug and Narcotic Control; Fentanyl; Germany; Narcotics; Phenethylamines; Psychotropic Drugs; Switzerland; Synthetic Drugs; United Nations
PubMed: 31256819
DOI: 10.1016/j.scijus.2019.03.005 -
Nutrition and Health Mar 2023The overall prevalence of diabetes in the world has risen substantially in the past several decades, so have complications and mortalities associated with it.... (Review)
Review
The overall prevalence of diabetes in the world has risen substantially in the past several decades, so have complications and mortalities associated with it. Prevention strategies for diabetes thus become an urgent public health need for reducing the burden of diabetes. Ractopamine, a β1/2-adrenergic receptor agonist, has been approved for use in finishing swine, cattle, and turkey in countries where meat exporting brings tremendous economic benefits. This leanness enhancer is recently found to be a full agonist at trace amine-associated receptor 1 also. A thorough literature review was performed to assess possible effects of ractopamine on glucose metabolism. Activating β-adrenoceptor could lead to glucose-lowering effects independent of insulin while activation on trace amine-associated receptor 1 induces an incretin-like signaling on insulin-secreting pancreatic β-cells. Accordingly, it is hypothesized that long-term consuming meat containing ractopamine might lower the risk of type 2 diabetes.
Topics: Humans; Animals; Swine; Cattle; Adrenergic beta-Agonists; Diabetes Mellitus, Type 2; Phenethylamines; Meat; Insulins
PubMed: 35702043
DOI: 10.1177/02601060221108146 -
Chemical Research in Toxicology Jan 20162,5-Dimethoxy-N-benzylphenethylamines (NBOMes) are very potent 5-HT2AR agonists. Illicit use of these psychedelic compounds has emerged in recent years, and several...
2,5-Dimethoxy-N-benzylphenethylamines (NBOMes) are very potent 5-HT2AR agonists. Illicit use of these psychedelic compounds has emerged in recent years, and several fatalities have been linked to their recreational use. In its [(11)C]-labeled form, one NBOMe (25B-NBOMe) was recently developed as a PET-ligand for clinical investigations of 5HT2AR ([(11)C]Cimbi-36). Herein, we have identified the phase I and phase II metabolites of 25B-NBOMe in pigs as well as in humans. We find that the primary route of metabolism is 5'-demethylation, followed by conjugation to glucuronic acid. Carbon-11 labeling of 25B-NBOMe in three different positions followed by in vivo evaluation in pigs and humans corroborated these findings.
Topics: Animals; Hallucinogens; Humans; Microsomes, Liver; Molecular Structure; Phenethylamines; Positron-Emission Tomography; Swine
PubMed: 26669514
DOI: 10.1021/acs.chemrestox.5b00450 -
Journal of Analytical Toxicology Mar 2023Six fatalities have occurred from the ingestion of a combination of new psychoactive substances (NPSs), 4-fluoroamphetamine (4FA) and...
Six fatalities have occurred from the ingestion of a combination of new psychoactive substances (NPSs), 4-fluoroamphetamine (4FA) and 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) over a 9-month period. Four of these fatalities (one older female and three young males) were from direct adverse effects of drugs, and one each from a fall while being intoxicated and during restraint. All cases were subject to full postmortem examinations that included collection of femoral blood. The four drug-caused fatalities had postmortem blood concentrations for 4FA and 25C-NBOMe of 330-682 ng/L (median 417) and 1.4-12 ng/mL (median 4.3), respectively. The other two cases (both young males) where death was considered to have been caused indirectly by drug intoxication had 4FA and 25C-NBOMe postmortem concentrations of 21 and 123 ng/mL, and 1.8 and 4.5 ng/mL, respectively. None of these cases showed concentrations of drugs that suggested use of high recreational doses. In one drug-caused death, capsules and a brown powder obtained from the scene were found to contain a mixture of these two NPSs. With the exception of one drug-caused death, other drugs were detected; however, the effects of the two NPSs together were regarded as the primary triggers for the deaths. There were no consistent symptoms or pathology in these cases; however, agitation/aggression was observed in two cases prior to their collapse, with seizures in possibly three cases. Pulmonary and/or cerebral edema was noted in three cases. Potentially significant natural disease (a mildly enlarged heart) was only observed in one drug-caused case. These cases illustrate a possible increased risk of sudden death with this combination of drugs, both of which can elevate serotonin concentrations as well as act as strong stimulants. These cases also illustrate the difficulty in detecting NPS in cases where no prior information is available that might suggest their use.
Topics: Male; Humans; Female; Phenethylamines; Amphetamines; Benzylamines
PubMed: 35975553
DOI: 10.1093/jat/bkac059 -
Bioorganic Chemistry Dec 2022In this study, a series of novel β-lactam derivatives were synthesized with yields ranging from 41 % to 91 %, and their antimicrobial activities were investigated...
In this study, a series of novel β-lactam derivatives were synthesized with yields ranging from 41 % to 91 %, and their antimicrobial activities were investigated against bacterial and fungal isolates that cause nosocomial infections. The results revealed that the novel β-lactam derivatives, especially compound 19, showed antibacterial activities ranging from 0.98 to 250 µg/mL. In contrast, the compounds showed no antifungal activity against fungal isolates. Following that, biochemical (Nitrocefin) investigation of compounds with antibacterial activity was carried out, as well as their effects on the β-lactamase enzyme. According to the results, the compounds inhibited the β-lactamase enzyme against bacterial isolates. Furthermore, the anticancer activity and toxicity profiles of β-lactam derivatives were also studied against colorectal cancer (Caco-2), the most common type of cancer, and non-human dermal fibroblast cell line. The results revealed that compound 19 was shown the best anticancer activity and lowest toxicity profile among other compounds. Therefore, these compounds, especially compound 19, could be useful in the treatment of colorectal cancer and related nosocomial infections. Furthermore, the potential of being an antibiotic can be put forward by investigating the resistant mechanism and further pharmacological studies.
Topics: Humans; beta-Lactams; beta-Lactamases; Caco-2 Cells; Anti-Bacterial Agents; Cross Infection; Colorectal Neoplasms; Phenethylamines; Microbial Sensitivity Tests
PubMed: 36274387
DOI: 10.1016/j.bioorg.2022.106212 -
Journal of Analytical Toxicology Feb 2023Various synthetic drugs have appeared over the past years across the world, and phenethylamine derivatives are among them; indeed, aromatic fluoro analogs of...
Various synthetic drugs have appeared over the past years across the world, and phenethylamine derivatives are among them; indeed, aromatic fluoro analogs of methamphetamine and amphetamine have been in the illicit drug market since the early 2000s. Although they are currently widely abused across the world, little information is available on their metabolism and toxicology. Recently, we came across an alleged 2-fluoromethamphetamine (2-FMA) drug abuse case. The urine obtained from the alleged abuser was analyzed as part of a criminal investigation. 2-FMA, 2-fluoroamphetamine (2-FAP) and some related compounds were detected by liquid chromatography-tandem mass spectrometry. In forensic science, both an "unchanged" drug and its metabolite(s) need to be detected in urine to verify the illicit drug use. Notably, the detection of 2-FAP, which is a plausible 2-FMA metabolite, is insufficient as evidence of 2-FMA use because 2-FAP is widely available and may be present as such in taken liquids. In this study, we synthesized analytical standards for N-hydroxy 2-FMA (N-OH-2-FMA) and two diastereomers of 2-fluoroephedrine, which are plausible metabolites of 2-FMA. Using these standards, the urine specimen was found to contain N-OH-2FMA and one diastereomer of 2-fluoroephedrine; moreover, the concentrations of these compounds were successfully determined. The results of our study suggest that N-hydroxylation and aliphatic hydroxylation are the characteristic metabolic pathways of 2-FMA compared with that of methamphetamine. This evidence indicates that both N-OH-2-FMA and 2-fluoroephedrine are plausible candidates as analytical targets for drug-use certification in forensic science.
Topics: Humans; Methamphetamine; Amphetamine; Mass Spectrometry; Substance-Related Disorders; Illicit Drugs; Substance Abuse Detection
PubMed: 35562170
DOI: 10.1093/jat/bkac026 -
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