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Neuropharmacology Apr 2023Serotoninergic psychedelics induced extensive alterations in perception and cognition, which has been attributable to its disruptive effect on oscillatory rhythms of...
Serotoninergic psychedelics induced extensive alterations in perception and cognition, which has been attributable to its disruptive effect on oscillatory rhythms of prefrontal cortex. However, there is a lack of information how serotoninergic psychedelics affect the intra-prefrontal network, which intrinsically interact to accomplish perceptual processing. Uncovering the altered neural network caused by psychedelics helps to understand the mechanisms of their psychoactive effects and contribute to develop biological markers of psychedelic effects. In present study, we investigated the effects of substituted phenethylamine psychedelic 25C-NBOMe on neural oscillations in the intra-prefrontal and hippocampal-prefrontal network. The effective dose of 25C-NBOMe (0.1 mg/kg) disrupting sensorimotor gating in male Sprague-Dawley rats was used to observe its effects on neural oscillations in the prelimbic cortex, anterior cingulate cortex, orbitofrontal cortex (OFC) and hippocampus CA1. The power of high frequency oscillation (HFO, 120-150 Hz) was potentiated by 25C-NBOMe selectively in the OFC, with peaking at 20-30 min after treatment. 25C-NBOMe strengthened HFO coherence within the intra-prefrontal, rather than hippocampal-prefrontal network. Potentiated HFO in the OFC had a strong positive correlation with the strengthened inter-prefrontal HFO coherence by 25C-NBOMe. The 25C-NBOMe-induced alterations of rhythmic patterns were prevented by pre-treatment with selective serotonin 2A receptor antagonist MDL100,907. These results demonstrate that OFC rhythmic activity in HFO is relatively susceptible to substituted phenethylamine and potentially drives drug-induced rhythmic coherence within intra-prefrontal regions. Our findings provide additional insight into the neuropathophysiology of the psychoactive effects of psychedelics and indicate that the altered HFO might be applied as a potential biological marker of psychedelic effect.
Topics: Rats; Male; Animals; Hallucinogens; Rats, Sprague-Dawley; Phenethylamines; Disease Susceptibility; Prefrontal Cortex
PubMed: 36724866
DOI: 10.1016/j.neuropharm.2023.109452 -
Journal of Neural Transmission.... 1990Phenylethylamine is present in brain in tiny quantities, it is heterogeneously distributed and present in synaptosomes, and it is synthesized and degraded very quickly.... (Review)
Review
Phenylethylamine in the CNS: effects of monoamine oxidase inhibiting drugs, deuterium substitution and lesions and its role in the neuromodulation of catecholaminergic neurotransmission.
Phenylethylamine is present in brain in tiny quantities, it is heterogeneously distributed and present in synaptosomes, and it is synthesized and degraded very quickly. If deuterium is substituted for hydrogen on the alpha carbon of the side chain then it exhibits profound isotope effects to MAO and its penetration and persistence in the brain is considerably enhanced. In the presence of MAO-B inhibitors treatment with reserpine causes reciprocal changes to PE and DA suggesting a functional relationship between them and after unilateral lesions of the substantia nigra an ipsilateral reduction in striatal PE is seen suggesting again a co-relationship with DA. Following iontophoresis PE has been shown to exhibit indirect sympathomimetic effects but in addition when applied at low currents concurrently with DA or NA it causes post synaptically a substantial potentiation in the actions of the latter amines. As a result of this and other data PE has been proposed to be a neuromodulator of catecholaminergic transmission.
Topics: Animals; Catecholamines; Central Nervous System; Enzyme Inhibitors; Humans; Monoamine Oxidase; Phenethylamines; Phenylalanine
PubMed: 2193105
DOI: 10.1007/978-3-7091-9050-0_12 -
Biological Psychiatry May 1985To examine the biochemical effects of 10-30 mg/day L-deprenyl, measurement of 24-hr urinary output of phenylethylamine (PEA), 3-methoxy 4-hydroxy phenylethyleneglycol... (Clinical Trial)
Clinical Trial
To examine the biochemical effects of 10-30 mg/day L-deprenyl, measurement of 24-hr urinary output of phenylethylamine (PEA), 3-methoxy 4-hydroxy phenylethyleneglycol (MHPG), and L-deprenyl's amphetamine metabolites were carried out before and during the treatment of atypical depressives. Platelet monoamine oxidase (MAO) activity was also assessed. With L-deprenyl 10-30 mg/day, the expected MAO B inhibition occurred, as indicated by significant increase in urinary PEA excretion and virtual disappearance of platelet MAO activity. Twenty-five to 33% of the daily dose of L-deprenyl was recovered as urinary methamphetamine or amphetamine. Excretion of MHPG was significantly decreased with L-deprenyl 10-20 mg/day. Overall, the results suggest that L-deprenyl's antidepressant effects are mediated by some mechanism other than, or in addition to, MAO B inhibition.
Topics: Adult; Clinical Trials as Topic; Depressive Disorder; Dextroamphetamine; Dose-Response Relationship, Drug; Female; Glycols; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Monoamine Oxidase; Phenethylamines; Selegiline
PubMed: 3921065
DOI: 10.1016/0006-3223(85)90027-7 -
Chemical Research in Toxicology May 2016The popularity of designer phenethylamines such as synthetic cathinones ("bath salts") has led to increased reports of life-threatening hyperthermia. The diversity of...
The popularity of designer phenethylamines such as synthetic cathinones ("bath salts") has led to increased reports of life-threatening hyperthermia. The diversity of chemical modifications has resulted in the toxicological profile of most synthetic cathinones being mostly uncharacterized. Here, we investigated the thermogenic effects of six recently identified designer phenethylamines (4-methylmethamphetamine, methylone, mephedrone, butylone, pentylone, and MDPV) and compared these effects to the established thermogenic agent 3,4-methylenedioxymethamphetamine (MDMA). Specifically, we determined the impact of a β-ketone, α-alkyl, or pyrrolidine functional group on core-body temperature changes. Sprague-Dawley rats (n = 5-6) were administered a dose (30 mg/kg, sc) of a designer phenethylamine or MDMA, and core body temperature measurements were recorded at 30 min intervals for 150 min post treatment. MDMA elicited the greatest maximum temperature change (ΔTmax), and this effect was significantly greater than that of its β-ketone analogue, methylone. Temperature-area under the curves (TAUCs) and ΔTmax were also significantly different between 4-methylmethamphetamine (4-MMA) and its β-ketone analogue mephedrone. Lengthening the α-alkyl chain of methylone to produce butylone and pentylone significantly attenuated the thermogenic response on both TAUCs and ΔTmax compared to those of methylone; however, butylone and pentylone were not different from each other. Pyrrolidine substitution on the N-terminus of pentylone produces 3,4-methylenedioxypyrovalerone (MDPV), which did not significantly alter core body temperature. Thermogenic comparisons of MDMA vs methylone and 4-MMA vs mephedrone indicate that oxidation at the benzylic position significantly attenuates the hyperthermic response. Furthermore, either extending the α-alkyl chain to ethyl and propyl (butylone and pentylone, respectively) or extending the α-alkyl chain and adding a pyrrolidine on the N-terminus (MDPV) significantly blunted the thermogenic effects of methylone. Overall, the present study provides the first structure-activity relationship in vivo toxicological analysis of designer phenethylamines.
Topics: Animals; Fever; Ketones; Male; Phenethylamines; Rats; Rats, Sprague-Dawley; Sympathomimetics
PubMed: 26954347
DOI: 10.1021/acs.chemrestox.6b00030 -
Drug Testing and Analysis Apr 2020Due to the much lower production costs but similar effects to lysergic acid diethylamide (LSD), phenethylamine derivatives are sold as a cheaper replacement or...
Due to the much lower production costs but similar effects to lysergic acid diethylamide (LSD), phenethylamine derivatives are sold as a cheaper replacement or deceptively as LSD itself. These potent hallucinogenic substances can lead to severe intoxication, thus a more profound understanding of their use is required. This includes the elucidation of the manufacturing processes for the commonly used blotter papers and the assessment of the risk of overdosing because of a heterogeneous distribution on the blotter papers. Besides the rapid detection of the analytes, the manufacturing process was elucidated by three different imaging techniques and liquid chromatography-mass spectrometry (LC-MS). A blotter paper sample, containing the two hallucinogenic phenethylamine derivatives 25I-NBOMe and 25C-NBOMe, was analyzed by complementary techniques such as micro x-ray fluorescence (μXRF), laser ablation (LA)-inductively coupled plasma-optical emission spectroscopy (ICP-OES), matrix assisted laser desorption ionization (MALDI)-MS, and with LC-MS after extraction. Using the signal from chlorine and iodine within the compounds, μXRF proved to be the fastest, cheapest and easiest method for identification, requiring no sample preparation at all. LA-ICP-OES provided three-dimensional information of the elements in the blotter paper. These results helped to confirm the assumption that manufacturers spray the compounds onto the paper. Whereas μXRF and LA-ICP-OES detected signals for chlorine and iodine, MALDI-MS-imaging showed the molecular distribution of both analytes. LC-MS analyses as a complementary method support the imaging results. Quantitative results for different drug hotspots revealed a heterogeneous distribution of the drugs on the blotter paper implying an inherent risk of overdosing for consumers.
Topics: Benzylamines; Chromatography, High Pressure Liquid; Dimethoxyphenylethylamine; Hallucinogens; Lysergic Acid Diethylamide; Paper; Phenethylamines; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 31846172
DOI: 10.1002/dta.2751 -
Arzneimittel-Forschung 1977A series of phenylisopropylamine derivatives are compared with the correspondent beta-methoxy- and beta-hydroxy-phenethylamine compounds. Unlike amphetamine, the...
A series of phenylisopropylamine derivatives are compared with the correspondent beta-methoxy- and beta-hydroxy-phenethylamine compounds. Unlike amphetamine, the beta-methoxy phenethylamine has no anorectic activity. This property appears only with the introduction of a CF3 group on the benzene nucleus. The racemic N-alkyl derivatives are more active than the racemic or even the levorotatory N-benzyl compound. The beta-hydroxy-phenethylamines are devoid of anorectic activity.
Topics: Animals; Appetite; Appetite Depressants; Lethal Dose 50; Male; Mice; Phenethylamines; Rats; Structure-Activity Relationship
PubMed: 576809
DOI: No ID Found -
Journal of Bacteriology Jul 2013The disA gene encodes a putative amino acid decarboxylase that inhibits swarming in Proteus mirabilis. 5' rapid amplification of cDNA ends (RACE) and deletion analysis...
The disA gene encodes a putative amino acid decarboxylase that inhibits swarming in Proteus mirabilis. 5' rapid amplification of cDNA ends (RACE) and deletion analysis were used to identify the disA promoter. The use of a disA-lacZ fusion indicated that FlhD(4)C(2), the class I flagellar master regulator, did not have a role in disA regulation. The putative product of DisA, phenethylamine, was able to inhibit disA expression, indicating that a negative regulatory feedback loop was present. Transposon mutagenesis was used to identify regulators of disA and revealed that umoB (igaA) was a negative regulator of disA. Our data demonstrate that the regulation of disA by UmoB is mediated through the Rcs phosphorelay.
Topics: Artificial Gene Fusion; Bacterial Proteins; DNA Transposable Elements; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Genes, Reporter; Locomotion; Mutagenesis, Insertional; Phenethylamines; Promoter Regions, Genetic; Proteus mirabilis; beta-Galactosidase
PubMed: 23687266
DOI: 10.1128/JB.00039-13 -
Xenobiotica; the Fate of Foreign... Jun 2007The in vivo metabolism of 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), a ring-substituted psychoactive phenethylamine, was studied in rat. Male Wistar rats were...
The in vivo metabolism of 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), a ring-substituted psychoactive phenethylamine, was studied in rat. Male Wistar rats were administered 10 mg/kg 2C-T-7 hydrochloride orally, and 24-h urine fractions were collected. After enzymatic hydrolysis of the urine sample, the metabolites were extracted by liquid-liquid extraction and analyzed by liquid chromatography/mass spectrometry. 2C-T-7-sulfoxide, N-acetyl-2C-T-7-sulfoxide, N-acetyl-2,5-dimethoxy-4-methylthiophenethylamine-sulfoxide, N-acetyl-2,5-dimethoxy-4-(2-hydroxypropylthio)phenethylamine-sulfoxide, and N-acetyl-2,5-dimethoxy-4-(2-hydroxypropylthio)phenethylamine-sulfone were detected as the primary metabolites of 2C-T-7. These findings suggest that sulfoxidation, sulfone formation, hydroxylation of the propyl side chain at the beta-position, and S-depropylation followed by methylation of thiol were the major metabolic pathways of 2C-T-7 in rat.
Topics: Animals; Chromatography, Liquid; Male; Mass Spectrometry; Phenethylamines; Psychotropic Drugs; Rats; Rats, Wistar
PubMed: 17614010
DOI: 10.1080/00498250701329302 -
Materials Science & Engineering. C,... Aug 2017Terpolymers of poly (Lysine-co-N, N-Bis (acryloyl) cystamine-co-β-Phenethylamine) (PLBP) were synthesized in one-pot by Michael addition terpolymerization. The...
Terpolymers of poly (Lysine-co-N, N-Bis (acryloyl) cystamine-co-β-Phenethylamine) (PLBP) were synthesized in one-pot by Michael addition terpolymerization. The terpolymers self-assembled into nano-sized spherical micelles (84-123nm) with narrow distributions. The surface charge of the nanomicelles (NMs) was depended on solution's pH and showed negative values under physiological conditions (pH7.4), which was beneficial for long circulation without non-specific protein adsorption. Doxorubicin (DOX) was effectively loaded into the NMs for controlled release. The in vitro release profiles exhibited obvious pH and reduction sensitivities in response to the environment mimicking tumor cells. The MTT assays demonstrated that blank NMs were biocompatible, and drug-laden NMs showed a significant cytotoxicity on Hela cells. The NMs could be potentially applied as smart drug delivery systems in cancer therapy.
Topics: Delayed-Action Preparations; Doxorubicin; HeLa Cells; Humans; Hydrogen-Ion Concentration; Micelles; Nanostructures; Oxidation-Reduction; Phenethylamines
PubMed: 28532112
DOI: 10.1016/j.msec.2017.03.203 -
Nutrients May 2024Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) and alkylamines (AA) are widely present in these supplements....
Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) and alkylamines (AA) are widely present in these supplements. Although the health effects of these analogues are not well understood yet, they are hypothesised to be agonists of adrenergic (ADR) and trace amine-associated receptors (TAARs). Therefore, we aimed to pharmacologically characterise these compounds by investigating their activating properties of ADRs and TAAR1 . The potency and efficacy of the selected PEAs and AAs was studied by using cell lines overexpressing human ADRα/α/α/α/α/β/β or TAAR1. Concentration-response relationships are expressed as percentages of the maximal signal obtained by the full ADR agonist adrenaline or the full TAAR1 agonist phenethylamine. Multiple PEAs activated ADRs (EC = 34 nM-690 µM; E = 8-105%). Almost all PEAs activated TAAR1 (EC = 1.8-92 µM; E = 40-104%). Our results reveal the pharmacological profile of PEAs and AAs that are often used in food supplements. Several PEAs have strong agonistic properties on multiple receptors and resemble potencies of the endogenous ligands, indicating that they might further stimulate the already activated sympathetic nervous system in exercising athletes via multiple mechanisms. The use of supplements containing one, or a combination of, PEA(s) may pose a health risk for their consumers.
Topics: Phenethylamines; Humans; Receptors, G-Protein-Coupled; Dietary Supplements; Receptors, Adrenergic; HEK293 Cells
PubMed: 38892500
DOI: 10.3390/nu16111567