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Physiology & Behavior May 2022Predator odors provide critical information to prey species allowing them to gage potential threat via the detection of semiochemicals called kairomones. Recent reports...
Characterizing the effects of 2-phenylethylamine and coyote urine on unconditioned and conditioned defensive behaviors in adolescent male and female Long-Evans hooded rats.
Predator odors provide critical information to prey species allowing them to gage potential threat via the detection of semiochemicals called kairomones. Recent reports indicate that the commercially available predator odor coyote urine (CU), and to a lesser extent 2-phenylethylamine (PEA), induce innate defensive behaviors in adult rats and mice. The aim of the present study was to see if the defense-inducing effects of CU and PEA would extend to adolescents. Specifically, we evaluated the ability of CU and PEA to induce unconditioned and conditioned defensive behavior in predator-odor naïve adolescent male and female Long-Evans hooded rats. An additional group of males were exposed to the non-predatory aversive odor formalin to control for potential general aversive properties of the odorants. The data revealed that in males, both CU and PEA, but not formalin induced measures of risk assessment, whereas CU and formalin produced avoidance of the odor source. In partial contrast, both CU and PEA produced avoidance of the odor source and increased measures of risk assessment in females. Surprisingly males failed to show any measures of defense during the cue+context conditioning test trial. In contrast, in females both odorants produced marginal effects during re-exposure to the conditioning context, with CU inducing conditioned avoidance and PEA inducing conditioned risk assessment. We conclude that commercially available CU and PEA elicit a moderate defensive profile compared to previous reports examining cat fur/skin odor in male and female adolescent rats. Future research needs to examine additional concentrations of the odorants to determine if a more robust unconditioned defensive profile (e.g., freezing) can be induced by these predator odors, and whether the defensive profile responds to standard anxiolytic drugs.
Topics: Animals; Female; Male; Mice; Rats; Behavior, Animal; Conditioning, Psychological; Coyotes; Formaldehyde; Odorants; Phenethylamines; Predatory Behavior; Rats, Long-Evans
PubMed: 35122825
DOI: 10.1016/j.physbeh.2022.113726 -
Journal of Animal Science Dec 2016One hundred ninety-two steers (BW = 354 ± 23.5 kg) were used in a randomized block design to evaluate the effects of ionophore and ractopamine hydrochloride (RH)... (Randomized Controlled Trial)
Randomized Controlled Trial
One hundred ninety-two steers (BW = 354 ± 23.5 kg) were used in a randomized block design to evaluate the effects of ionophore and ractopamine hydrochloride (RH) supplementation strategies on performance and carcass characteristics. Twelve pens of 4 steers were assigned to each of the following treatments: unsupplemented control (CON), laidlomycin propionate (12.1 mg/kg DM) with or without RH (LPRH and LP, respectively), and monensin sodium (36.4 mg/kg DM) with RH (MSRH). Steers were fed for 151 d, of which respective treatments received RH (Actogain; Zoetis, Florham Park, NJ) at a rate of 300 mg/(animal · d) for the final 32 d. Laidlomycin was removed from the LPRH treatment during this period, as no combination feeding has been approved. Upon harvest, carcass data were collected by trained personnel, and subsequent analysis of the LM was conducted to estimate tenderness using Warner-Bratzler shear force (WBSF). Prior to RH supplementation, both LP and LPRH had greater ADG ( ≤ 0.02) and G:F ( < 0.01) than CON, whereas MSRH was intermediate. During the final 32 d, MSRH improved G:F ( ≤ 0.02) compared to all other treatments and tended to increase ADG over unsupplemented controls ( = 0.05). Cattle receiving LP without RH had significantly greater BW at d 151 than CON ( = 0.02), whereas both RH treatments tended to improve final BW ( ≤ 0.09). Ionophores improved ADG ( ≤ 0.03) and G:F ( < 0.01) for the entire feeding period, and although LP-supplemented cattle had greater DMI for the final 32 d than both RH treatments ( ≤ 0.01), intakes for the 151-d trial were similar among treatments. Carcass weights were greater ( = 0.04) in cattle fed LP with no RH than CON, where cattle yielded an average of 12 kg more HCW. Ractopamine increased LM area in MSRH-supplemented cattle ( = 0.03) and tended to increase LM area for steers receiving LPRH ( = 0.07). Longissimus steaks of MSRH-supplemented cattle had greater WBSF values than CON ( = 0.04) after 7 d of postmortem aging and greater WBSF values than LPRH steaks after 28 d ( = 0.03). All other carcass and WBSF measurements were similar among treatments. The results of this study indicate that LP supplementation without RH may yield a performance similar to and carcass responses associated with the administration of a β-agonist. These results also suggest that performance and carcass characteristics for cattle fed LP are similar to those of cattle fed monensin throughout the feeding period.
Topics: Adrenergic beta-Agonists; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Composition; Cattle; Diet; Dietary Supplements; Ionophores; Male; Monensin; Phenethylamines; Trimethylsilyl Compounds
PubMed: 28046158
DOI: 10.2527/jas.2016-0841 -
Microbial Biotechnology Jul 2023Multidrug efflux pumps are among the main Pseudomonas aeruginosa antibiotic-resistance determinants. Besides, efflux pumps are also involved in other relevant activities...
Multidrug efflux pumps are among the main Pseudomonas aeruginosa antibiotic-resistance determinants. Besides, efflux pumps are also involved in other relevant activities of bacterial physiology, including the quorum sensing-mediated regulation of bacterial virulence. Nevertheless, despite the relevance of efflux pumps in bacterial physiology, their interconnection with bacterial metabolism remains obscure. The effect of several metabolites on the expression of P. aeruginosa efflux pumps, and on the virulence and antibiotic resistance of this bacterium, was studied. Phenylethylamine was found to be both inducer and substrate of MexCD-OprJ, an efflux pump involved in P. aeruginosa antibiotic resistance and in extrusion of precursors of quorum-sensing signals. Phenylethylamine did not increase antibiotic resistance; however, the production of the toxin pyocyanin, the tissue-damaging protease LasB and swarming motility were reduced in the presence of this metabolite. This decrease in virulence potential was mediated by a reduction of lasI and pqsABCDE expression, which encode the proteins that synthesise the signalling molecules of two quorum-sensing regulatory pathways. This work sheds light on the interconnection between virulence and antibiotic-resistance determinants, mediated by bacterial metabolism, and points to phenylethylamine as an anti-virulence metabolite to be considered in the study of therapies against P. aeruginosa infections.
Topics: Humans; Pseudomonas aeruginosa; Virulence; Quorum Sensing; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Phenethylamines; Virulence Factors; Bacterial Proteins; Pseudomonas Infections; Biofilms
PubMed: 36976480
DOI: 10.1111/1751-7915.14252 -
Fundamental & Clinical Pharmacology Dec 2018
Topics: France; Humans; Phenethylamines; Piperidines
PubMed: 30417492
DOI: 10.1111/fcp.12407 -
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 -
The Journal of Pharmacology and... Jan 2021Dietary supplements often contain additives not listed on the label, including -ethyl homologs of amphetamine such as ,-diethylphenethylamine (DEPEA). Here, we examined...
Dietary supplements often contain additives not listed on the label, including -ethyl homologs of amphetamine such as ,-diethylphenethylamine (DEPEA). Here, we examined the neurochemical and cardiovascular effects of -ethylphenethylamine (AEPEA), -methyl--ethylphenethylamine (MEPEA), and DEPEA as compared with the effects of amphetamine. All drugs were tested in vitro using uptake inhibition and release assays for monoamine transporters. As expected, amphetamine acted as a potent and efficacious releasing agent at dopamine transporters (DAT) and norepinephrine transporters (NET) in vitro. AEPEA and MEPEA were also releasers at catecholamine transporters, with greater potency at NET than DAT. DEPEA displayed fully efficacious release at NET but weak partial release at DAT (i.e., 40% of maximal effect). In freely moving, conscious male rats fitted with biotelemetry transmitters for physiologic monitoring, amphetamine (0.1-3.0 mg/kg, s.c.) produced robust dose-related increases in blood pressure (BP), heart rate (HR), and motor activity. AEPEA (1-10 mg/kg, s.c.) produced significant increases in BP but not HR or activity, whereas DEPEA and MEPEA (1-10 mg/kg, s.c.) increased BP, HR, and activity. In general, the phenethylamine analogs were approximately 10-fold less potent than amphetamine. Our results show that -ethylphenethylamine analogs are biologically active. Although less potent than amphetamine, they produce cardiovascular effects that could pose risks to humans. Given that MEPEA and DEPEA increased locomotor activity, these substances may also have significant abuse potential. SIGNIFICANCE STATEMENT: The -ethyl homologs of amphetamine have significant cardiovascular, behavioral, and neurochemical effects in rats. Given that these compounds are often not listed on the ingredient labels of dietary supplements, these compounds could pose a risk to humans using these products.
Topics: Animals; Blood Pressure; Butylamines; Catecholamine Plasma Membrane Transport Proteins; Central Nervous System Stimulants; Dietary Supplements; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Heart Rate; Male; Methamphetamine; Movement; Norepinephrine Plasma Membrane Transport Proteins; Phenethylamines; Rats; Rats, Sprague-Dawley
PubMed: 33082158
DOI: 10.1124/jpet.120.000129 -
Journal of the American Chemical Society May 2017The rate of hydrogen-deuterium exchange (HDX) in aqueous droplets of phenethylamine has been determined with submillisecond temporal resolution by mass spectrometry...
The rate of hydrogen-deuterium exchange (HDX) in aqueous droplets of phenethylamine has been determined with submillisecond temporal resolution by mass spectrometry using nanoelectrospray ionization with a theta-capillary. The average speed of the microdroplets is measured using microparticle image velocimetry. The droplet travel time is varied from 20 to 320 μs by changing the distance between the emitter and the heated inlet to the mass spectrometer and the voltage applied to the emitter source. The droplets were found to accelerate by ∼30% during their observable travel time. Our droplet imaging shows that the theta-capillary produces two Taylor cone-jets (one per channel), causing mixing to take place from droplet fusion in the Taylor spray zone. Phenethylamine (ϕCHCHNH) was chosen to study because it has only one functional group (-NH) that undergoes rapid HDX. We model the HDX with a system of ordinary differential equations. The rate constant for the formation of -NHD from -NH is 3660 ± 290 s, and the rate constant for the formation of -NHD from -NHD is 3330 ± 270 s. The observed rates are about 3 times faster than what has been reported for rapidly exchangeable peptide side-chain groups in bulk measurements using stopped-flow kinetics and NMR spectroscopy. We also applied this technique to determine the HDX rates for a small 10-residue peptide, angiotensin I, in aqueous droplets, from which we found a 7-fold acceleration of HDX in the droplet compared to that in bulk solution.
Topics: Deuterium Exchange Measurement; Nanotechnology; Particle Size; Phenethylamines; Spectrometry, Mass, Electrospray Ionization; Water
PubMed: 28481522
DOI: 10.1021/jacs.7b03541 -
Journal of Molecular Recognition : JMR Oct 2021A novel spectrofluorimetric sensing platform was designed for Ractopamine measurement in aqueous and plasma samples. d-penicillamine functionalized graphene quantum dots...
A novel spectrofluorimetric sensing platform was designed for Ractopamine measurement in aqueous and plasma samples. d-penicillamine functionalized graphene quantum dots (DPA-GQDs) was utilized as a fluorescence probe, which was synthesized through the pyrolysis of citric acid in the presence of DPA. This one-pot down-top strategy causes to high-yield controllable synthesis method. The reaction time and probe concentration were optimized. Then, the fluorescence intensity of aqueous samples containing different Ractopamine concentrations and 500 ppm DPA-GQDs were measured at 25°C with an excitation wavelength of 274 nm. The sensing platform was also applied to detect Ractopamine in untreated plasma samples. The fluorescence spectroscopy technique responses indicated a linear relationship between the peak fluorescence intensity and ractopamine concentration in the range of 0.25-15 ppm with low limit of quantification of 0.25 ppm was for aqueous and plasma samples, respectively.
Topics: Adrenergic beta-Agonists; Blood Chemical Analysis; Fluorescent Dyes; Graphite; Humans; Penicillamine; Phenethylamines; Quantum Dots; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared
PubMed: 33970548
DOI: 10.1002/jmr.2903 -
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 -
Journal of Pharmaceutical and... Feb 201725B-NBOMe and 25C-NBOMe are potent 5-HT receptor agonists that have been associated with inducing hallucinogenic effects in drug users and severe intoxications. This...
Metabolic fate and detectability of the new psychoactive substances 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe) and 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) in human and rat urine by GC-MS, LC-MS, and LC-HR-MS/MS...
25B-NBOMe and 25C-NBOMe are potent 5-HT receptor agonists that have been associated with inducing hallucinogenic effects in drug users and severe intoxications. This paper describes the identification of their metabolites in rat and human urine by liquid chromatography (LC)-high resolution (HR)-MS/MS, the comparison of metabolite formation in vitro and in vivo and in different species, the general involvement of human cytochrome-P450 (CYP) isoenzymes on their metabolism steps, and their detectability by standard urine screening approaches (SUSAs) using GC-MS, LC-MS, or LC-HR-MS/MS. Both NBOMe derivatives were mainly metabolized by O-demethylation, O,O-bis-demethylation, hydroxylation, and combinations as well as by glucuronidation and sulfation of the main phase I metabolites. For 25B-NBOMe, 66 metabolites could be identified and 69 for 25C-NBOMe. After application of low doses of both substances to rats, they were detectable mainly via their metabolites by both LC-based SUSAs. In case of acute intoxication, it was possible to detect 25B-NBOMe and its metabolites in an authentic human urine sample when using the GC-MS SUSA in addition to the LC-based SUSAs. Initial CYP activity screening revealed the involvement of CYP1A2 and CYP3A4 in hydroxylation and CYP2C9 and CYP2C19 in O-demethylation. The presented study demonstrated that 25B-NBOMe and 25C-NBOMe were extensively metabolized and detectable by both LC-based SUSAs.
Topics: Animals; Anisoles; Benzylamines; Chromatography, Liquid; Gas Chromatography-Mass Spectrometry; Humans; Insecta; Male; Phenethylamines; Psychotropic Drugs; Rats; Rats, Wistar; Tandem Mass Spectrometry
PubMed: 27915193
DOI: 10.1016/j.jpba.2016.11.040