Search Results (21)

Background: Driving is a coordinated psychomotor activity that involves reaction time, attention, and decision-making. Psychoactive substances such as 2-phenylethylamine (PEA) derivatives and opioids may affect these functions and contribute to traffic safety. This systematic review revealed the effects of the selected PEA derivatives and opioids on psychomotor performance among drivers and potential road safety outcomes. Methods: The review followed PRISMA 2020 standards. Using the PICO method, we conducted a systematic search in Embase, PubMed, and Web of Science (2000–2025). Included studies involved adult participants and quantified the effect of PEA derivatives or opioids on driving-related psychomotor function. Thirty-one articles, such as randomized controlled trials, crossover studies, observational studies, and simulator-based studies, were examined. Risk of bias was evaluated using the RoB2 tool. Results: Evidence indicates therapeutic amphetamine and methylphenidate doses can enhance psychomotor function and safety in patients with ADHD. Recreational or high-dose use of methamphetamine and MDMA is associated with impaired coordination, variable speed, and increased impulsivity. Opioid effects are tolerance- and dose-dependent. Small therapeutic doses of fentanyl in chronically treated patients do not notably impair driving. On the other hand, methadone and tramadol commonly cause somnolence, retardation of reaction, and increased accident risk. Conclusions: The impact of opioids and PEA derivatives on psychomotor function is multifactorial, depending on dose, time, route of administration, and patient status. These substances can either improve or impair driving safety. The findings confirm the need for individual-specific pharmacotherapy treatment. They also highlight the importance of further studies to formulate evidence-based clinical and legislative guidelines. Full article

Recent findings indicate that human microbiota can excrete trace amines, dopamine, and serotonin. These neurotransmitters (NTs) can either affect classical neurotransmitter signaling or directly trigger trace amine-associated receptors (TAARs), with still unclear consequences for host physiology. Compared to gut microbiota, less information is available on the role of skin microbiota in NT production. To explore this, 1909 skin isolates, mainly from the genera Staphylococcus, Bacillus, and Corynebacterium, were tested for NT production. Only 6.7% of the isolates were capable of producing NTs, all of which belonged to the Staphylococcus genus. Based on substrate specificity, we identified two distinct profiles among the NT producers. One group primarily produced tryptamine (TRY) and phenylethylamine (PEA), while the other mainly produced tyramine (TYM) and dopamine (Dopa). These differing production profiles could be attributed to the activity of two distinct aromatic amino acid decarboxylase enzymes, SadA and TDC, responsible for generating the TRY/PEA and TYM/Dopa product spectra, respectively. SadA and TDC orthologues differ in structure and size; SadA has approximately 475 amino acids, whereas the TDC type consists of about 620 amino acids. The genomic localization of the respective genes also varies: tdc genes are typically found in small, conserved gene clusters, while sadA genes are not. The heterologous expression of sadA and tdc in Escherichia coli yielded the same product spectrum as the parent strains. The possible effects of skin microbiota-derived NTs on neuroreceptor signaling in the human host remain to be investigated. Full article

Most of the biogenic amines are naturally found in fermented foods as a consequence of amino acid decarboxylation. Their formation is ascribable to microorganisms (starters, contaminants and autochthonous) present in the food matrix. The concentration of these molecules is important for food security reasons, as they are involved in food poisoning illnesses. The most frequent amines found in foods are histamine, putrescine, cadaverine, tyramine, tryptamine, phenylethylamine, spermine and spermidine. One of the most risk-prone foods are cheeses, mostly ripened ones, which could easily accumulate amines due to their peculiar manufacturing process and ripening. Cheeses represent a pivotal food in our diet, providing for nutrients such as amino acids, calcium, vitamins and others; thus, since they are widely consumed, it is important to evaluate the presence of toxic molecules to avoid consumers’ poisoning. This review aimed to gather general information on the role of biogenic amines, their formation, the health issues and the microorganisms and processes that produce/reduce them, with a focus on their content in different types of cheese (from soft to hard cheeses) and the biotic and abiotic factors that influence their formation or reduction and concentration. Finally, a multivariate analysis was performed on the biogenic amine content, derived from data available in the literature, to obtain more information about the factors influencing their presence in cheeses. Full article

To improve the electrochromic (EC) properties of sol–gel-derived WO₃ films, a series of organic small molecules, such as dopamine (DA), catechol, tyramine, phenol and 2-phenylethylamine, were added into peroxotungstic acid precursor sols as structure-directing additives, and five modified WO₃ films were prepared by a simple and low-cost complexation-assisted sol–gel method. The effects of the above additives on the EC properties of the modified WO₃ films have been studied in detail. Compared with the pure WO₃ polycrystalline film, all the modified films combine the advantages of nanocrystalline and amorphous phases and show higher EC properties attributed to the unique nanocrystal-embedded amorphous structure. The results indicate that different additives with different numbers and types of functional groups (hydroxyl and amino groups) can change the microstructure, morphology, and thus electrochemical and EC properties of the films in various degrees. The additives, in order of their strong interactions with the sols, are DA, catechol, tyramine, phenol and 2-phenylethylamine, primarily depending on the number of hydroxyl groups. Of all the additives, DA with both catechol hydroxyl and amino groups shows the most positive effect; that is, the WO₃ film modified with DA exhibits the best EC properties in terms of contrast, switching speed, stability, and coloration efficiency. Full article

Palladium-catalyzed C-H activation reactions have attracted the attention of organic researchers due to their unique high selectivity, broad functional group tolerance, and high efficiency, and they are widely used in natural products and asymmetric synthesis. Here, we report an example of enantioselective C-H alkenylation between β-alkyl phenylethylamine compounds and styrenes with Boc-L-lle-OH as the ligand and nosylamide as the directing group. This reaction is applicable to styrene containing various electron-deficient and electron-donating substitutions and may be utilized for the synthesis of benzoazepine compounds. Full article

Sixty-three men (15–35 years of age) regularly training in Danish gyms and supplement users were interviewed about the use of supplemental protein and food supplements, intake of caffeine- and (-)-epigallocathechin-3-gallate (EGCG)-containing supplements and beverages and any experienced adverse effects. Protein powder (60%), fish oil (54%) and multivitamin/mineral supplements (41%) were the most popular products. The daily supplementary protein intake (mean 0.42 g/kg body weight, users only) in adult men contributed substantially to their protein intake and exceeded the recommended allowance (0.83 g/kg body weight) for six adult participants (14%). Thirty-eight percent of the adult men exceeded the daily caffeine intake presumed to be safe (400 mg) with coffee as the main contributor. Thirty percent drank green tea and among this percentage, two participants had an extreme daily intake (1.5 and 2 -L). EGCG intake could not be estimated from the food supplements due to the lack of label information. Eighteen participants (29%) reported having experienced adverse effects but seventeen did not consult a physician or report the adverse effect to the Danish food authority. The most common adverse effects were insomnia, shaking, headache and palpitations, itching of the skin and stinging. Pre-workout products accounted for 53% of the adverse effects. Three adverse effects came after intake of two brands of supplements known to have contained substances such as 1,3-dimethylamine or derivatives of phenylethylamines previously having caused serious adverse effects. Full article

Stereoselectivity is well known and very pronounced in drug metabolism and receptor binding. However, much less is known about stereoselectivity in drug membrane transport. Here, we characterized the stereoselective cell uptake of chiral phenylethylamine derivatives by human monoamine transporters (NET, DAT, and SERT) and organic cation transporters (OCT1, OCT2, and OCT3). Stereoselectivity differed extensively between closely related transporters. High-affinity monoamine transporters (MATs) showed up to 2.4-fold stereoselective uptake of norepinephrine and epinephrine as well as of numerous analogs. While NET and DAT preferentially transported (S)-norepinephrine, SERT preferred the (R)-enantiomer. In contrast, NET and DAT showed higher transport for (R)-epinephrine and SERT for (S)-epinephrine. Generally, MAT stereoselectivity was lower than expected from their high affinity to several catecholamines and from the high stereoselectivity of some inhibitors used as antidepressants. Additionally, the OCTs differed strongly in their stereoselectivity. While OCT1 showed almost no stereoselective uptake, OCT2 was characterized by a roughly 2-fold preference for most (R)-enantiomers of the phenylethylamines. In contrast, OCT3 transported norphenylephrine and phenylephrine with 3.9-fold and 3.3-fold preference for their (R)-enantiomers, respectively, while the para-hydroxylated octopamine and synephrine showed no stereoselective OCT3 transport. Altogether, our data demonstrate that stereoselectivity is highly transporter-to-substrate specific and highly diverse even between homologous transporters. Full article

While a few derivatives of cinnamamides exhibited anti-inflammatory and/ or analgesic activity, in this study, we developed a highly efficient method for the synthesis of cinnamamides from methyl cinnamates and phenylethylamines catalyzed by Lipozyme^® TL IM in continuous-flow microreactors. The reaction parameters and broad substrate range of the new method was studied. Maximum conversion (91.3%) was obtained under the optimal condition of substrate molar ratio of 1:2 (methyl 4-chlorocinnamate: phenylethylamine) at 45 $°\mathrm{C}$ for about 40 min. The remarkable features of this work include short residence time, mild reaction conditions, easy control of the reaction process, and that the catalyst can be recycled or reused, which provide a rapid and economical strategy for the synthesis and design of cinnamamide derivatives for further research on drug activity. Full article

A series of chelated dehydroacetic acid–imine-based ligands L¹H~L⁴H was synthesized by reacting dehydroacetic acid with 2-t-butylaniline, (S)-1-phenyl-ethylamine, 4-methoxylbenzylamine, and 2-(aminoethyl)pyridine, respectively, in moderate yields. Ligands L¹H~L⁴H reacted with AlMe₃ in toluene to afford corresponding compounds AlMe₂L¹ (1), AlMe₂L² (2), AlMe₂L³ (3), and AlMe₂L⁴ (4). All the ligands and aluminum compounds were characterized by IR spectra, ¹H and ¹³C NMR spectroscopy. Additionally, the ligands L¹H~L⁴H and corresponding aluminum derivatives 1, 3, and 4 were characterized by single-crystal X-ray diffractometry. The catalytic activities using these aluminum compounds as catalysts for the ε-caprolactone ring-opening polymerization (ROP) and styrene oxide-CO₂ coupling reactions were studied. The results show that increases in the reaction temperature and selective solvent intensify the conversions of ε-caprolactone to polycaprolactone. Regarding the coupling reactions of styrene oxide and CO₂, the conversion rate is over 90% for a period of 12 h at 90 °C. This strategy dispenses the origination of cyclic styrene carbonates, which is an appealing concern because of the transformation of CO₂ into an inexpensive, renewable and easy excess carbon feedstock. Full article

The analysis of psychoactive substances in hair is of great importance for both clinical and forensic toxicologists since it allows one to evaluate past and continuative exposure to xenobiotics. In particular, a new challenge is represented by new psychoactive substances: Among this new class of drugs of abuse, synthetic cathinone and phenethylamine derivatives are often detected in biological samples. Hence, there is a growing need to develop new analytical procedures or improve old ones in order to conduct evaluations of these emerging substances. This study is a systematic review of all the instrumental and experimental data available in the literature. A total of 32 articles were included in the review. Acidic solvents proved to be the most reliable solutions for extraction. Gas chromatography and liquid chromatography coupled to tandem mass spectrometric and high-resolution mass spectrometric systems represent the majority of the involved instrumental techniques. Sensitivity must be maintained at the pg/mg level to detect any occurrences up to occasional consumption. In total, 23 out of 32 articles reported real positive samples. The most frequently detected substance in hair was mephedrone, followed by butylone, methylone, MDPV, and α-pyrrolidinophenone-type substances. Full article

An ever-increasing need exists within the forensic laboratories to develop analytical processes for the qualitative and quantitative determination of a broad spectrum of new psychoactive substances. Phenylethylamine derivatives are among the major classes of psychoactive substances available on the global market and include both amphetamine analogues and synthetic cathinones. In this work, an ultra-high-performance liquid chromatography-positive ion electrospray ionization tandem mass spectrometric method (UHPLC-ESI-MS/MS) has been developed and fully validated for the determination of 19 psychoactive substances, including nine amphetamine-type stimulants and 10 synthetic cathinone derivatives, in premortem and postmortem whole blood. The assay was based on the use of 1 mL premortem or postmortem whole blood, following solid phase extraction prior to the analysis. The separation was achieved on a Poroshell 120 EC-C18 analytical column with a gradient mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water in 9 min. The dynamic multiple reaction monitoring used in this work allowed for limit of detection (LOD) and lower limit of quantitation (LOQ) values of 0.5 and 2 ng mL⁻¹, respectively, for all analytes both in premortem and postmortem whole blood samples. A quadratic calibration model was used for the 12 quantitative analytes over the concentration range of 20–2000 ng mL⁻¹, and the method was shown to be precise and accurate both in premortem and postmortem whole blood. The method was applied to the analysis of real cases and proved to be a valuable tool in forensic and clinical toxicology. Full article

Nine new secondary metabolites, including six isocoumarin analogues, 7-hydroxyoospolactone (1), 7-methoxyoospolactone (2), 7-methoxy-9-hydroxyoospolactone (3), 10-acetoxy-9-hydroxyoospolactone (4), 6-dehydroxysescandelin (5), parapholactone (6), and three compounds with a rare skeleton of isocoumarin coupled with phenylethylamine, namely paraphamide A (12), paraphamide B (13), and paraphamide C (14), together with five known compounds, oospolactone (7), 8-O-methyloospolactone (8), 10-hydroxyoospolactone (9), 9,10-dihydroxyoospolactone (10), and oospoglycol (11), were isolated and identified from the marine-derived fungus Paraphoma sp. CUGBMF180003. Their chemical structures were determined using spectroscopic data, including HRESIMS and 1D and 2D NMR techniques. Furthermore, the stereogenic carbons in 5 and 14 were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra. The carbon skeleton of 12–14 was identified as the first example of isocoumarin coupled with phenylethylamine derivatives. All of these compounds were examined for antimicrobial activities against Candida albicans and Staphylococcus aureus. Both 1 and 6 showed antibacterial activity against S. aureus with MIC values of 12.5 μg/mL. Full article

Yeast starters for cocoa fermentation are usually tested according to their enzymatic activities in terms of mucilage degradation and flavor improvement, disregarding their influence on the production or elimination of toxic compounds as biogenic amines (BAs), important for human health. In this work, we tested 145 strains belonging to 12 different yeast species and isolated from the Colombian fermented cocoa beans (CB) for their capability of producing BAs in vitro. Sixty-five strains were able to decarboxylate at least one of the amino acids tested. Pichia kudriavzevii ECA33 (Pk) and Saccharomyces cerevisiae 4 (Sc) were selected to evaluate their potential to modulate BAs, organic acids, and volatile organic compounds (VOCs) accumulation during a simulated cocoa fermentation. The growth of Sc or Pk in the presence of CB caused a significant reduction (p < 0.05) of 2-phenylethylamine (84% and 37%) and cadaverine (58% and 51%), and a significant increase of tryptamine and putrescine with a strong influence of temperature in BA formation and degradation. In addition, our findings pointed out that Pk induced a major production of fatty acid- and amino acid-derived VOCs, while Sc induced more VOCs derived from fatty acids metabolism. Our results suggest the importance of considering BA production in the choice of yeast starters for cocoa fermentation. Full article

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. Full article

Objective: N-(2-methoxy) benzyl-phenethylamine (NBOMe) derivatives have a high affinity to the serotonin receptor 2A and emerged as new psychedelic agents. We report the case of a 30-year-old man admitted to the hospital because of acute ischemia of the left arm with clinical symptoms of pallor, pulselessness, paresthesia, and a motoric deficit. The patient had a history of schizophrenia and drug abuse and disclosed during the hospital stay the sublingual intake of a substance bought as 25I-NBOMe the night before the ischemic event. Methods: Routine clinical diagnostics including among others color-coded duplex sonography and computed tomography angiography (CTA) were performed. The remainder of the drugs was analyzed using high performance liquid chromatography. Results: Initial color-coded duplex sonography of the upper left limb showed pathological flow profiles of the axillary, brachial, ulnar, and radial artery with a reduced diameter of the ulnar (0.9 mm) and radial (1.1 mm) artery. In consequence, peripheral vasospasm, distal arterial thrombosis, or arterial embolization was anticipated. As therapeutic measures, the patient immediately received intravenous systemic vasodilators (alprostadil) and therapeutic anticoagulation with low molecular weight heparin. Instant symptom improvement was observed within the first day after therapy initiation. The subsequently performed CTA of the heart and left arm showed no signs of thrombotic material. Treatment was continued for five days and the patient was released thereafter having completely normalized perfusion in his left arm. Outpatient treatment was continued with calcium-channel blockers, as the patient had also displayed arterial hypertension. Drug analysis retrieved a composition of the isomers 25I-NBOMe, 25C-NBOMe, and 25H-NBOMe as well as traces of pentylon. Conclusion: NBOMe ingestion implicates the risk of peripheral vasospasms with severe, limb-threatening ischemia. Full article