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https://www.readbyqxmd.com/read/28601767/pooled-human-liver-preparations-heparg-or-hepg2-cell-lines-for-metabolism-studies-of-new-psychoactive-substances-a-study-using-mdma-mdbd-butylone-mdppp-mdpv-mdpb-5-mapb-and-5-api-as-examples
#1
Lilian H J Richter, Veit Flockerzi, Hans H Maurer, Markus R Meyer
Metabolism studies play an important role in clinical and forensic toxicology. Because of potential species differences in metabolism, human samples are best suitable for elucidating metabolism. However, in the case of new psychoactive substances (NPS), human samples of controlled studies are not available. Primary human hepatocytes have been described as gold standard for in vitro metabolism studies, but there are some disadvantages such as high costs, limited availability, and variability of metabolic enzymes...
May 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28600798/inhibition-of-p38mapk-signaling-prevents-epidermal-blistering-and-alterations-of-desmosome-structure-induced-by-pemphigus-autoantibodies-in-human-epidermis
#2
D T Egu, E Walter, V Spindler, J Waschke
BACKGROUND: Pemphigus vulgaris (PV) is a skin blistering disease caused by autoantibodies targeting the desmosomal adhesion proteins desmoglein (Dsg) 3 and 1. The mechanisms underlying pemphigus skin blistering are not fully elucidated but p38MAPK activation is one of the signaling events necessary for full loss of cell cohesion. However, it is unclear whether ultrastructural hallmarks of desmosome morphology as observed in patients' lesions are mediated by p38MAPK signaling. OBJECTIVE: In this study, we tested the relevance of p38MAPK for blister formation and the ultrastructural changes induced by PV autoantibodies in human skin...
June 10, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28598863/characterization-of-the-discriminative-stimulus-effects-of-3-4-methylenedioxypyrovalerone-in-male-sprague-dawley-rats
#3
Michael D Berquist, Lisa E Baker
Recreational use of 3,4-methylenedioxypyrovalerone (MDPV) in the early 2000s prompted numerous scientific investigations of its behavioral and neurochemical effects. The purpose of this study was to further characterize the interoceptive stimulus effects of MDPV using a validated in-vivo drug-detection assay. Male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg MDPV from saline under a fixed ratio 20 (FR 20) schedule of food reinforcement. After stimulus control was established with MDPV (∼35 training sessions), substitution tests were commenced with drugs from several chemical classes, including drugs with predominantly dopaminergic actions [MDPV, D-amphetamine, (+)-methamphetamine, (-)-cocaine], drugs with predominantly serotonergic actions [(+)-lysergic acid diethylamide, (+)-fenfluramine], and drugs with both serotonergic and dopaminergic actions (3,4-methylenedioxymethamphetamine, 4-methylmethcathinone)...
June 8, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28570297/reinforcing-effects-of-abused-bath-salts-constituents-3-4-methylenedioxypyrovalerone-and-%C3%AE-pyrrolidinopentiophenone-and-their-enantiomers
#4
Brenda M Gannon, Kenner C Rice, Gregory T Collins
Synthetic cathinones found in abused 'bath salts' preparations are chiral molecules. Racemic 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (α-PVP) are two common constituents of these preparations that have been reported to be highly effective reinforcers; however, the relative contribution of each enantiomer toward these effects has not been determined. Thus, male Sprague-Dawley rats were trained to respond for racemic MDPV or α-PVP (n=9/drug), with full dose-response curves for the racemate and the S and R enantiomers of MDPV and α-PVP generated under a progressive ratio schedule of reinforcement...
May 31, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28527032/methylone-and-mdpv-activate-autophagy-in-human-dopaminergic-sh-sy5y-cells-a-new-insight-into-the-context-of-%C3%AE-keto-amphetamines-related-neurotoxicity
#5
Maria João Valente, Cristina Amaral, Georgina Correia-da-Silva, José Alberto Duarte, Maria de Lourdes Bastos, Félix Carvalho, Paula Guedes de Pinho, Márcia Carvalho
Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity has hitherto not been investigated. In the present study, we show that two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), elicit morphological changes consistent with autophagy and neurodegeneration, including formation of autophagic vacuoles and neurite retraction in dopaminergic SH-SY5Y cells...
May 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28427995/conditioned-taste-avoidance-conditioned-place-preference-and-hyperthermia-induced-by-the-second-generation-bath-salt-%C3%AE-pyrrolidinopentiophenone-%C3%AE-pvp
#6
Katharine H Nelson, Briana J Hempel, Matthew M Clasen, Kenner C Rice, Anthony L Riley
BACKGROUND: α-Pyrrolidinopentiophenone (α-PVP) has been reported to be rewarding in a variety of pre-clinical models. Given that a number of drugs of abuse have both rewarding and aversive effects, the balance of which influences addiction potential, the present study examined the aversive properties of α-PVP by assessing its ability to induce taste avoidance. This assessment was made in a combined taste avoidance/place conditioning design that also allowed an evaluation of the relationship between α-PVP's aversive and rewarding effects...
April 17, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28396142/atypical-binding-at-dopamine-and-serotonin-transporters-contribute-to-the-discriminative-stimulus-effects-of-mephedrone
#7
Alyssa F DeLarge, Laura L Erwin, Peter J Winsauer
Mephedrone (4-methylmethcathinone), a constituent of the recreational substances known as "bath salts", is a synthetic cathinone that can produce auditory and visual hallucinations, as well as problematic cardiovascular effects. This study compared the discriminative stimulus effects of mephedrone (0.32-10 mg/kg) with other prototypical drugs of abuse: cocaine (0.56-32 mg/kg), d-amphetamine (0.18-3.2 mg/kg), ketamine (1.8-18 mg/kg), phencyclidine (PCP, 1-5.6 mg/kg), heroin (1-10 mg/kg), 2,5-dimethoxy-4-iodoamphetamine (R-DOI, 0...
June 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28352261/analysis-of-evolutionary-processes-of-species-jump-in-waterfowl-parvovirus
#8
Wentao Fan, Zhaoyu Sun, Tongtong Shen, Danning Xu, Kehe Huang, Jiyong Zhou, Suquan Song, Liping Yan
Waterfowl parvoviruses are classified into goose parvovirus (GPV) and Muscovy duck parvovirus (MDPV) according to their antigenic features and host preferences. A novel duck parvovirus (NDPV), identified as a new variant of GPV, is currently infecting ducks, thus causing considerable economic loss. This study analyzed the molecular evolution and population dynamics of the emerging parvovirus capsid gene to investigate the evolutionary processes concerning the host shift of NDPV. Two important amino acids changes (Asn-489 and Asn-650) were identified in NDPV, which may be responsible for host shift of NDPV...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28347165/synthetic-cathinones-in-southern-germany-characteristics-of-users-substance-patterns-co-ingestions-and-complications
#9
Katrin Romanek, Jochen Stenzel, Sabrina Schmoll, Verena Schrettl, Stefanie Geith, Florian Eyer, Christian Rabe
OBJECTIVE: To define the characteristics of synthetic cathinone users admitted to hospital including clinical and laboratory parameters and the complications of use. DESIGN: Retrospective single-center study of patients treated for acute cathinone intoxication and complications of cathinone use between January 2010 and January 2016. SETTING: A specialized clinical toxicology unit at an academic tertiary care center in Southern Germany serving a population of about 4 million...
July 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28328032/product-ion-tandem-mass-spectrometric-differentiation-of-regioisomeric-side-chain-groups-in-cathinone-derivatives
#10
Younis Abiedalla, Jack DeRuiter, C Randall Clark
RATIONALE: Precursor materials are available to prepare aminoketone drugs containing regioisomeric propyl and isopropyl side-chain groups related to the drug alpha-pyrrovalerone (Flakka) and MDPV (3,4-methylenedioxypyrrovalerone). These compounds yield equivalent regioisomeric iminium cation base peaks in electron ionization mass spectrometry (EI-MS). METHODS: The propyl and isopropyl side-chain groups related to alpha-pyrrovalerone and MDPV were prepared and evaluated in EI-MS and tandem mass spectrometry (MS/MS) product ion experiments...
July 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28325154/the-behavioral-profile-of-methylenedioxypyrovalerone-mdpv-and-%C3%AE-pyrrolidinopentiophenone-pvp-a-systematic-review
#11
Cornel N Stanciu, Thomas M Penders, Samantha A Gnanasegaram, Elvin Pirapakaran, Juvraj S Padda, Jeeven S Padda
BACKGROUND: New psychoactive substances are emerging at an alarming rate. With novel structures and properties they produce unique behavioral characteristics during intoxication. Synthetic cathinones are some of the most common. More and more are presenting to emergency departments due to consequences of use. Aside from isolated reports, little is known about these compounds. OBJECTIVE: Here we review literature pertaining to two common synthetic cathinones, MDPV and alphaPVP, and correlate clinically with guidance on management of intoxications...
March 21, 2017: Current Drug Abuse Reviews
https://www.readbyqxmd.com/read/28286575/chiral-determination-of-3-4-methylenedioxypyrovalerone-enantiomers-in-rat-serum
#12
Michael D Hambuchen, Howard P Hendrickson, S Michael Owens
The emerging stimulant drug of abuse (3,4)-methylenedioxypyrovalerone [(R,S)-MDPV] is self-administered as a racemic mixture by intranasal, iv, oral, and smoking routes. The individual enantiomers are known to have widely different pharmacological effects, with (S)-MDPV showing much greater potency than (R)-MDPV in pharmacological testing. The goal of these studies was to develop and validate an analytical method for quantitation of (R)-MDPV, (S)-MDPV and (R,S)-MDPV in small volumes of rat serum using a chiral separation column and liquid chromatography-mass spectrometry...
January 28, 2017: Analytical Methods: Advancing Methods and Applications
https://www.readbyqxmd.com/read/28262947/exposure-of-adolescent-mice-to-3-4-methylenedioxypyrovalerone-increases-the-psychostimulant-rewarding-and-reinforcing-effects-of-cocaine-in-adulthood
#13
R López-Arnau, M A Luján, L Duart-Castells, D Pubill, J Camarasa, O Valverde, E Escubedo
BACKGROUND AND PURPOSE: 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with powerful psychostimulant effects. It selectively inhibits the dopamine transporter (DAT) and is 10-50-fold more potent as a DAT blocker than cocaine, suggesting a high abuse liability. The main objective of the present study was to assess the consequences of an early (adolescence) MDPV exposure on the psychostimulant, rewarding and reinforcing effects induced by cocaine in adult mice. EXPERIMENTAL APPROACH: Twenty-one days after MDPV pretreatment (1...
May 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28251297/glutamate-carboxypeptidase-ii-gcpii-inhibitor-2-pmpa-reduces-rewarding-effects-of-the-synthetic-cathinone-mdpv-in-rats-a-role-for-n-acetylaspartylglutamate-naag
#14
Callum Hicks, Ryan A Gregg, Sunil U Nayak, Lee Anne Cannella, Giana J Schena, Christopher S Tallarida, Allen B Reitz, Garry R Smith, Scott M Rawls
RATIONALE: Metabotropic glutamate 2 and 3 (mGluR2/3) receptors are implicated in drug addiction as they limit excessive glutamate release during relapse. N-acetylaspartylglutamate (NAAG) is an endogenous mGluR2/3 agonist that is inactivated by the glutamate carboxypeptidase II (GCPII) enzyme. GCPII inhibitors, and NAAG itself, attenuate cocaine-seeking behaviors. However, their effects on the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) have not been examined. OBJECTIVES: We determined whether withdrawal following repeated MDPV administration alters GCPII expression in corticolimbic regions...
June 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28226266/parallel-artificial-liquid-membrane-extraction-of-new-psychoactive-substances-in-plasma-and-whole-blood
#15
Linda Vårdal, Hilde-Merete Askildsen, Astrid Gjelstad, Elisabeth Leere Øiestad, Hilde Marie Erøy Edvardsen, Stig Pedersen-Bjergaard
Parallel artificial liquid membrane extraction (PALME) was combined with ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and the potential for screening of new psychoactive substances (NPS) was investigated for the first time. PALME was performed in 96-well format comprising a donor plate, a supported liquid membrane (SLM), and an acceptor plate. Uncharged NPS were extracted from plasma or whole blood, across an organic SLM, and into an aqueous acceptor solution, facilitated by a pH gradient...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28219712/the-combination-of-mdpv-and-ethanol-results-in-decreased-cathinone-and-increased-alcohol-levels-study-of-such-pharmacological-interaction
#16
R López-Arnau, M Buenrostro-Jáuregui, P Muñoz-Villegas, J Rodríguez-Morató, A Ciudad-Roberts, L Duart, J Camarasa, R De la Torre, D Pubill, E Escubedo
Methylenedioxypyrovalerone (MDPV) is a new psychostimulant cathinone acting as a selective dopamine transporter blocker. Due to the concomitant consumption of ethanol (EtOH) and new psychoactive substances, it is of interest to explore a possible pharmacological interaction between MDPV and EtOH. In locomotor activity assays, EtOH (1g/kg i.p.) elicited a reduction in the stimulant effect induced by low doses of MDPV (0.1-0.3mg/kg, s.c.) in rats, jointly with a decrease in blood and brain MDPV concentrations...
February 17, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28212938/the-combined-effects-of-3-4-methylenedioxymethamphetamine-mdma-and-selected-substituted-methcathinones-on-measures-of-neurotoxicity
#17
Nicholas B Miner, James P O'Callaghan, Tamara J Phillips, Aaron Janowsky
The rise in popularity of substituted methcathinones (aka "bath salts") has increased the focus on their neurotoxic effects. Two commonly abused methcathinones, 3,4-methylenedioxymethcathinone (methylone, MDMC) and 3,4-methylenedioxypyrovalerone (MDPV), are often concomitantly ingested with the illicit drug 3,4-methylenedioxymethamphetamine (MDMA). To examine potential neurotoxic effects of these drug combinations, C57BL/6J mice were administered 4 i.p. injection of the drugs, at 2h intervals, either singularly: MDMA 15 or 30mg/kg, methylone 20mg/kg, MDPV 1mg/kg; or in combination: methylone/MDMA 20/15mg/kg, MDPV/MDMA 1/15mg/kg...
May 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28199890/gc-ms-gc-ms-ms-and-gc-ir-differentiation-of-desoxy-cathinone-derivatives-cyclic-tertiary-amines-related-to-mdpv
#18
Younis Abiedalla, Jack DeRuiter, C Randall Clark
The desoxy phenethylamine analogues in this study represent a combination of alkyl side-chain and cyclic amines (azetidine, pyrrolidine, piperidine and azepane) to yield a set of molecules of identical elemental composition as well as major mass spectral fragment ions (base peaks) of identical elemental composition. These desoxy phenethylamine analogues of the aminoketone designer drug, 3,4-methylenedioxy-pyrrovalerone (MDPV) related to the natural product cathinone were prepared from piperonal (3,4-methylenedioxybenzaldehyde) via the intermediate precursor ketones...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28187296/toxicological-investigation-of-forensic-cases-related-to-the-designer-drug-3-4-methylenedioxypyrovalerone-mdpv-detection-quantification-and-studies-on-human-metabolism-by-gc-ms
#19
Marcel Grapp, Christoph Kaufmann, Martin Ebbecke
3,4-methylenedioxypyrovalerone (MDPV) is a synthetic cathinone belonging to the class of α-pyrrolidinophenones that become increasingly popular as a designer psychostimulant. Here, we report a comprehensive collection of MDPV exposure with quantitative serum level confirmation in Germany. During the years 2014-2016, we could proof consumption of MDPV in 23 cases where urine and blood samples were submitted to our laboratory by the police of Lower Saxony. Most of the samples underwent systematic toxicological analysis by gas chromatography-mass spectrometry (GC-MS), where MDPV could be detected in urine and/or serum samples...
February 2, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28179474/individual-differences-in-the-relative-reinforcing-effects-of-3-4-methylenedioxypyrovalerone-under-fixed-and-progressive-ratio-schedules-of-reinforcement-in-rats
#20
Brenda M Gannon, Kayla I Galindo, Kenner C Rice, Gregory T Collins
The recreational use of designer drugs, including synthetic cathinones (bath salts), is associated with high levels of abuse and toxicity, and represents a growing threat to public health. 3,4-Methylenedioxypyrovalerone (MDPV) is a cocaine-like monoamine uptake inhibitor, and one of the most widely available and abused synthetic cathinones. The present study used male Sprague-Dawley rats to directly compare: (1) the acquisition of responding for MDPV and cocaine under a fixed ratio (FR) 1 schedule of reinforcement; (2) full dose-response curves for MDPV and cocaine under a FR5 schedule; and (3) progressive ratio (PR) schedules of reinforcement...
April 2017: Journal of Pharmacology and Experimental Therapeutics
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