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Novel Amphetamine

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https://www.readbyqxmd.com/read/27890676/combined-in-vitro-and-in-silico-approaches-to-the-assessment-of-stimulant-properties-of-novel-psychoactive-substances-the-case-of-the-benzofuran-5-mapb
#1
Michelle A Sahai, Colin Davidson, George Khelashvili, Vincenzo Barrese, Neelakshi Dutta, Harel Weinstein, Jolanta Opacka-Juffry
Novel psychoactive substances (NPS) are increasingly prevalent world-wide although their pharmacological characteristics are largely unknown; those with stimulant properties, due to interactions with the dopamine transporter (DAT), have addictive potential which their users may not realise. We evaluated the binding of 1-(1-benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB) to rat striatal DAT by means of quantitative autoradiography with [(125)I]RTI-121, and the effects of 5-MAPB on electrically-evoked dopamine efflux by fast-cyclic voltammetry in rat brain slices...
November 24, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27856682/capturing-schizophrenia-like-prodromal-symptoms-in-a-spinocerebellar-ataxia-17-transgenic-rat
#2
Davide Amato, Fabio Canneva, Huu Phuc Nguyen, Peter Bauer, Olaf Riess, Stephan von Hörsten, Christian P Müller
RATIONALE: The polyglutamine disease spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease leading to severe neurological symptoms during development. Additionally, patients affected by SCA17 display psychosis earlier than their motor disorders. OBJECTIVE: Here the putative psychotic phenotype and endophenotype of transgenic SCA17 rats was examined. METHODS: The expression of schizophrenia-like symptoms was evaluated over a longitudinal period before and after the onset of neurological symptoms in SCA17...
November 8, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27789102/nps-and-the-methadone-queue-spillages-of-space-and-time
#3
Liviu Alexandrescu
BACKGROUND: Between 2008 and 2013, powder-stimulants sold by 'head shops' as novel psychoactive substances (NPS) or 'legal highs' have displaced heroin among groups of injecting substance users in Bucharest, Romania. Rising HIV-infection rates and other medical or social harms have been reported to follow this trend. METHODS: The study builds on two sets of original (N=30) and existing (N=20) interview data and on observations collected mainly at the site of a methadone substitution treatment facility...
October 24, 2016: International Journal on Drug Policy
https://www.readbyqxmd.com/read/27756623/evidence-of-memory-generalization-in-contextual-locomotor-sensitization-induced-by-amphetamine
#4
Douglas Senna Engelke, Renato Filev, Luiz E Mello, Jair Guilherme Santos-Junior
Addiction is a multifactorial disease that comprises physiological mechanisms of learning and memory. Addict subjects have intense plasticity in cortical and limbic circuits during intoxication, abstinence or even in drug seeking behavior. Locomotor sensitization is a classic animal model of drug addiction that mimics the changes that occur in the transition from drug use to drug addiction. Several studies have demonstrated the importance of contextual associative processes in this task. However, whether the mechanisms of sensitization are maintained and precise over the time remain an open question...
October 15, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27753475/multivariate-curve-resolution-alternating-least-squares-analysis-of-high-resolution-liquid-chromatography-mass-spectrometry-data
#5
Melanie M Sinanian, Daniel W Cook, Sarah C Rutan, Dayanjan S Wijesinghe
Methods such as liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) are crucial for differentiating compounds with highly similar masses. This is a necessity when analyzing highly complex samples; however, the size of high-resolution LC-HRMS data sets can cause difficulties when applying advanced data analysis techniques. In this work, LC-HRMS analyses of known amphetamine samples and unknown bacterial lipid samples were carried out, and multivariate curve resolution-alternating least squares (MCR-ALS) was applied to the data to obtain mathematical separation of overlapped analyte signals...
November 1, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27663745/exposure-to-amphetamines-leads-to-development-of-amphetamine%C3%A2-type-stimulants%C3%A2-associated-cardiomyopathy-atsac
#6
Mahsa Jafari Giv
With rapidly rising prevalence of exposure to Amphetamine Type Stimulants (ATS), novel insights into cardiotoxic effects of this substance are being presented in the literature and remarkably ATS Associated Cardiomyopathy (ATSAC) is emerging as a novel cardiovascular condition with its distinctive pathogenesis, risk factors, clinical features and prognosis. A comprehensive systematic review was performed to explore and analyze the current evidence on the association between ATS exposure and development of cardiomyopathy, biological mechanisms involved in pathogenesis of ATSAC, risk factors, clinical features and course of patients with ATSAC...
September 24, 2016: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/27647375/design-and-synthesis-of-triarylacrylonitrile-analogues-of-tamoxifen-with-improved-binding-selectivity-to-protein-kinase-c
#7
Colleen Carpenter, Roderick J Sorenson, Yafei Jin, Szymon Klossowski, Tomasz Cierpicki, Margaret Gnegy, Hollis D Showalter
The clinical selective estrogen receptor modulator tamoxifen is also a modest inhibitor of protein kinase C, a target implicated in several untreatable brain diseases such as amphetamine abuse. This inhibition and tamoxifen's ability to cross the blood brain barrier make it an attractive scaffold to conduct further SAR studies toward uncovering effective therapies for such diseases. Utilizing the known compound 6a as a starting template and guided by computational tools to derive physicochemical properties known to be important for CNS permeable drugs, the design and synthesis of a small series of novel triarylacrylonitrile analogues have been carried out providing compounds with enhanced potency and selectivity for PKC over the estrogen receptor relative to tamoxifen...
November 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27598234/design-synthesis-and-biological-evaluation-of-fluorinated-imidazo-1-2-a-pyridine-derivatives-with-potential-antipsychotic-activity
#8
Monika Marcinkowska, Marcin Kołaczkowski, Krzysztof Kamiński, Adam Bucki, Maciej Pawłowski, Agata Siwek, Tadeusz Karcz, Barbara Mordyl, Gabriela Starowicz, Paulina Kubowicz, Elżbieta Pękala, Anna Wesołowska, Jerzy Samochowiec, Paweł Mierzejewski, Przemyslaw Bienkowski
Based on our recent finding that α1 selective GABA-A receptor potentiator-zolpidem-(a hypnotic drug) exerts antipsychotic-like effects in rats, we developed a series of fluorinated imidazo[1,2-a]pyridine derivatives as potential novel antipsychotic agents. The selected compounds displayed high affinity and positive allosteric modulator properties at the GABA-A receptor, enhanced metabolic stability and lack of hepatotoxicity. The most promising compound 2-(2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl)-N,N-dimethylethanamide (26) showed antipsychotic-like activity in amphetamine-induced hyperlocomotion test in rats (MED = 1 mg/kg) and was characterized by a longer duration of antipsychotic-like activity as compared to zolpidem...
August 26, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27538886/psychosis-associated-with-acute-recreational-drug-toxicity-a-european-case-series
#9
Odd Martin Vallersnes, Alison M Dines, David M Wood, Christopher Yates, Fridtjof Heyerdahl, Knut Erik Hovda, Isabelle Giraudon, Paul I Dargan
BACKGROUND: Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs. METHODS: The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries...
August 18, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27514281/dissociable-effects-of-the-prodrug-phendimetrazine-and-its-metabolite-phenmetrazine-at-dopamine-transporters
#10
Ernesto Solis, Julie A Suyama, Matthew F Lazenka, Louis J DeFelice, S Stevens Negus, Bruce E Blough, Matthew L Banks
Phendimetrazine (PDM) is a clinically available anorectic and a candidate pharmacotherapy for cocaine addiction. PDM has been hypothesized to function as a prodrug that requires metabolism to the amphetamine-like monoamine transporter substrate phenmetrazine (PM) to produce its pharmacological effects; however, whether PDM functions as an inactive prodrug or has pharmacological activity on its own remains unclear. The study aim was to determine PDM pharmacological mechanisms using electrophysiological, neurochemical, and behavioral procedures...
August 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27506653/ritanserin-sensitive-receptors-modulate-the-prosocial-and-the-anxiolytic-effect-of-mdma-derivatives-dob-and-pma-in-zebrafish
#11
Luisa Ponzoni, Mariaelvina Sala, Daniela Braida
Little is known about the pharmacological effects of amphetamine derivatives. In the present study, the effect on social preference and anxiety-like behavior of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), in comparison with 3,4 methylenedioxymethamphetamine (MDMA) was investigated in zebrafish, an emerging model to study emotional behavior in an inexpensive and quick manner. DOB (0.05-2mg/kg), PMA (0.0005-2mg/kg) or MDMA (0.25-20mg/kg), given i.m. to adult zebrafish, progressively increased the time spent in the proximity of nacre fish picture in a social preference test...
November 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27490334/a-novel-screening-method-for-64-new-psychoactive-substances-and-5-amphetamines-in-blood-by-lc-ms-ms-and-application-to-real-cases
#12
Fabio Vaiano, Francesco P Busardò, Diego Palumbo, Chrystalla Kyriakou, Alessia Fioravanti, Valeria Catalani, Francesco Mari, Elisabetta Bertol
Identification and quantification of new psychoactive substances (NPS), both in biological and non-biological samples, represent a hard challenge for forensic toxicologists. NPS are increasingly emerging on illegal drug market. Many cases of co-consumption of NPS and other substances have also been reported. Hence, the development of analytical methods aiming at the detection of a broad-spectrum of compounds (NPS and "traditional" drugs) could be helpful. In this paper, a fully validated screening method in blood for the simultaneous detection of 69 substances, including 64 NPS (28 synthetic cannabinoids, 19 synthetic cathinones, 5 phenethylamines, 3 indanes, 2 piperazines, 2 tryptamines, 2 phencyclidine, methoxetamine, ketamine and its metabolite) and 5 amphetamines (amphetamine, methamphetamine, MDMA, MDA, 3,4-methylenedioxy-N-ethylamphetamine - MDEA-) by a dynamic multiple reaction monitoring analysis through liquid chromatography - tandem mass spectrometry (LC-MS/MS) is described...
September 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27488574/a-randomized-crossover-study-to-assess-the-pharmacokinetics-of-a-novel-amphetamine-extended-release-orally-disintegrating-tablet-in-healthy-adults
#13
Jeffrey G Stark, Dorothy Engelking, Russ McMahen, Carolyn Sikes
OBJECTIVES: In this pharmacokinetic (PK) study in healthy adults, we sought to: (1) compare the PK properties of a novel amphetamine extended-release orally disintegrating tablet formulation (Adzenys XR-ODT™ [AMP XR-ODT]) to a reference extended-release mixed amphetamine salts (MAS ER) formulation and (2) assess the effect of food on AMP XR-ODT. METHODS: Forty-two adults were enrolled in a single-dose, open-label, 3-period, 3-treatment, randomized crossover study and received an 18...
September 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27448790/near-death-from-a-novel-synthetic-opioid-labeled-u-47700-emergence-of-a-new-opioid-class
#14
Aaron Schneir, Imir G Metushi, Christian Sloane, David J Benaron, Robert L Fitzgerald
BACKGROUND: In the last decade there has been a worldwide surge in the recreational abuse of novel psychoactive substances, particularly amphetamine derivatives and synthetic cannabinoids. Synthetic opioids such as AH-7921, MT-45, and U-47700, with structures distinct from those ever used therapeutically or described recreationally, have also recently emerged. CASE DETAILS: We report a patient who suffered respiratory failure and depressed level of consciousness after recreationally using a novel synthetic opioid labeled U-47700...
July 22, 2016: Clinical Toxicology
https://www.readbyqxmd.com/read/27421727/cocaine-and-amphetamine-regulated-transcript-a-novel-regulator-of-energy-homeostasis-expressed-in-a-subpopulation-of-pancreatic-islet-cells
#15
EDITORIAL
Patrick Gilon
Type 2 diabetes is characterised by chronic hyperglycaemia and its incidence is highly increased by exaggerated food consumption. It results from a lack of insulin action/production, but growing evidence suggests that it might also involve hyperglucagonaemia and impaired control of glucose homeostasis by the brain. In recent years, the cocaine and amphetamine-regulated transcript (CART) peptides have generated a lot of interest in the battle against obesity because, via the brain, they exert anorexic effects and they increase energy expenditure...
September 2016: Diabetologia
https://www.readbyqxmd.com/read/27380172/methamphetamine-consumption-inhibits-pair-bonding-and-hypothalamic-oxytocin-in-prairie-voles
#16
Caroline M Hostetler, Tamara J Phillips, Andrey E Ryabinin
Methamphetamine (MA) abuse has been linked to violence, risk-taking behaviors, decreased sexual inhibition, and criminal activity. It is important to understand mechanisms underlying these drug effects for prevention and treatment of MA-associated social problems. Previous studies have demonstrated that experimenter-administered amphetamine inhibits pair bonding and increases aggression in monogamous prairie voles. It is not currently known whether similar effects on social behaviors would be obtained under conditions during which the drug is voluntarily (actively) administered...
2016: PloS One
https://www.readbyqxmd.com/read/27376435/methylphenidate-triggered-ros-generation-promotes-caveolae-mediated-transcytosis-via-rac1-signaling-and-c-src-dependent-caveolin-1-phosphorylation-in-human-brain-endothelial-cells
#17
Vanessa Coelho-Santos, Renato Socodato, Camila Portugal, Ricardo A Leitão, Manuel Rito, Marcos Barbosa, Pierre-Olivier Couraud, Ignacio A Romero, Babette Weksler, Richard D Minshall, Carlos Fontes-Ribeiro, Teresa Summavielle, João B Relvas, Ana P Silva
Methylphenidate (MPH) is an amphetamine-like stimulant commonly prescribed for attention deficit hyperactivity disorder. Despite its widespread use, the cellular/molecular effects of MPH remain elusive. Here, we report a novel direct role of MPH on the regulation of macromolecular flux through human brain endothelial cells (ECs). MPH significantly increased caveolae-mediated transcytosis of horseradish peroxidase through ECs without affecting paracellular permeability. Using FRET-based live cell imaging, together with pharmacological inhibitors and lentiviral-mediated shRNA knockdown, we demonstrate that MPH promoted ROS generation via activation of Rac1-dependent NADPH oxidase (NOX) and c-Src activation at the plasma membrane...
July 4, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27343723/a-novel-immunoassay-for-quantitative-drug-abuse-screening-in-serum
#18
Sarah Schumacher, Harald Seitz
An immunoassay was established which enables a reliable quantification of serological drug samples. The assay is based on a competitive ELISA. In total nine drugs (amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), tetrahydrocannabinol (THC), phencyclidine (PCP), methadone, morphine, cocaine and benzoylecgonine) were tested. All reagents had to pass through a stringent validation process. Within the established test for three out of the nine drugs no cross-reactivity with any tested compounds, e...
September 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27336666/an-aptamer-folding-based-sensory-platform-decorated-with-nanoparticles-for-simple-cocaine-testing
#19
Emine Guler, Guliz Bozokalfa, Bilal Demir, Zinar Pinar Gumus, Bahar Guler, Ebru Aldemir, Suna Timur, Hakan Coskunol
The consumption of illicit drugs such as cannabis, cocaine, and amphetamines is still a major health and social problem, creating an abuse in adults especially. Novel techniques which estimate the drug of abuse are needed for the detection of newly revealed psychoactive drugs. Herein, we have constructed a combinatorial platform by using quantum dots (QDs) and gold nanoparticles (AuNPs) as well as a functional aptamer which selectively recognizes cocaine and its metabolite benzoylecgonine (BE). We have called it an aptamer folding-based sensory device (AFSD)...
June 23, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27329836/nesfatin-1-like-peptide-encoded-in-nucleobindin-1-in-goldfish-is-a-novel-anorexigen-modulated-by-sex-steroids-macronutrients-and-daily-rhythm
#20
Lakshminarasimhan Sundarrajan, Ayelén Melisa Blanco, Juan Ignacio Bertucci, Naresh Ramesh, Luis Fabián Canosa, Suraj Unniappan
Nesfatin-1 is an 82 amino acid anorexigen encoded in a secreted precursor nucleobindin-2 (NUCB2). NUCB2 was named so due to its high sequence similarity with nucleobindin-1 (NUCB1). It was recently reported that NUCB1 encodes an insulinotropic nesfatin-1-like peptide (NLP) in mice. Here, we aimed to characterize NLP in fish. RT- qPCR showed NUCB1 expression in both central and peripheral tissues. Western blot analysis and/or fluorescence immunohistochemistry determined NUCB1/NLP in the brain, pituitary, testis, ovary and gut of goldfish...
2016: Scientific Reports
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