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Novel Amphetamine

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https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#1
Jaakko Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
: Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases including drug addiction and Parkinson's disease. Because of its well-established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been extensively studied in various disorders with disturbed dopamine homeostasis. The outcomes from pre-clinical and clinical studies vary, however, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
January 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28063587/indirect-chiral-separation-of-8-novel-amphetamine-derivatives-as-potential-new-psychoactive-compounds-by-gc-ms-and-hplc
#2
Jennifer A Weiß, Kian Kadkhodaei, Martin G Schmid
Amphetamine and its derivatives gained high popularity on the illegal drug market. In the last few years, a lot of new psychoactive compounds structurally related to amphetamine, such as 4-fluoroamphetamine and 4-fluoromethamphetamine swamped the drug market. They were designed to circumvent prohibition of amphetamine and N-methylamphetamine and are distributed via the Internet. Often, a halogen atom is introduced into the phenyl ring of amphetamine to turn the illegal amphetamine legal. Since amphetamines possess a chiral centre, two enantiomers are available, which might differ in activity...
January 2017: Science & Justice: Journal of the Forensic Science Society
https://www.readbyqxmd.com/read/28062254/the-effects-of-d-govadine-on-conditioned-place-preference-with-d-amphetamine-or-food-reward
#3
Maya O Nesbit, Carine Dias, Anthony G Phillips
Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0...
January 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28039543/sigma-receptors-and-alcohol-use-disorders
#4
Valentina Sabino, Pietro Cottone
Although extensive research has focused on understanding the neurobiological mechanisms underlying alcohol addiction, pharmacological treatments for alcohol use disorders are very limited and not always effective. This constraint has encouraged the search for novel pharmacological targets for alcoholism therapy. Sigma receptors were shown to mediate some of the properties of cocaine and amphetamine, which was attributed to the direct binding of psychostimulants to these receptors. More recently, the role of sigma receptors in the rewarding and reinforcing effects of alcohol was also proposed, and it was suggested that their hyperactivity may result in excessive alcohol drinking...
December 31, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28029499/development-of-an-enantioseparation-method-for-novel-psychoactive-drugs-by-hplc-using-a-lux-%C3%A2-cellulose-2-column-in-polar-organic-phase-mode
#5
Magdalena Taschwer, Jörg Grascher, Martin G Schmid
Since the last decade, the hype of the recreational use of novel psychoactive drugs is still on its top in entire Europe. Every year, new derivatives enter the drug market and enlarge the broad spectrum of misused drugs. Many of these compounds contain a stereogenic centre and therefore two enantiomers exist. It is obvious that the pharmacological potency of the isomers differ as it is already known from various pharmaceutical ingredients. Therefore, the development of analytical methods for the chiral separation of new psychoactive substances is of great medical and forensic interest...
October 20, 2016: Forensic Science International
https://www.readbyqxmd.com/read/28003467/prefrontal-cortex-dysfunction-increases-susceptibility-to-schizophrenia-like-changes-induced-by-adolescent-stress-exposure
#6
Felipe V Gomes, Anthony A Grace
Stress during adolescence is a risk factor for schizophrenia, and medial prefrontal cortex (mPFC) dysfunction is proposed to interfere with stress control, increasing the susceptibility to stress. We evaluated the impact of different stressful events during adolescence (restraint stress [RS], footshock [FS], or the combination of FS and RS) on behaviors correlated with schizophrenia in rats as adults. At adulthood, animals were tested for anxiety responses (elevated plus-maze), cognitive function (novel-object recognition test) and dopamine (DA) system responsivity (locomotor response to amphetamine and DA neuron activity in the ventral tegmental area (VTA) using in vivo electrophysiology)...
December 21, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27996970/a-new-mouse-model-of-adhd-for-medication-development
#7
Petra Majdak, John R Ossyra, Jessica M Ossyra, Adam J Cobert, Gabrielle C Hofmann, Stephen Tse, Brent Panozzo, Elizabeth L Grogan, Anastassia Sorokina, Justin S Rhodes
ADHD is a major societal problem with increasing incidence and a stagnant track record for treatment advances. A lack of appropriate animal models has partly contributed to the incremental advance of this field. Hence, our goal was to generate a novel mouse model that could be useful for ADHD medication development. We reasoned that hyperactivity is a core feature of ADHD that could easily be bred into a population, but to what extent other hallmark features of ADHD would appear as correlated responses was unknown...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27936898/pharmacokinetics-of-a-novel-amphetamine-extended-release-orally-disintegrating-tablet-in-children-with-attention-deficit-hyperactivity-disorder
#8
Jeffrey G Stark, Dorothy Engelking, Russ McMahen, Carolyn Sikes
BACKGROUND: A novel formulation for treating attention-deficit/hyperactivity disorder (ADHD) has recently been developed-amphetamine extended-release orally disintegrating tablets (AMP XR-ODTs). In this study, we assessed the rate of absorption and exposure of AMP XR-ODT under fasted conditions in children with ADHD. METHODS: Children (6-12 years) with ADHD were enrolled in a single-dose, open-label, single-period pharmacokinetic (PK) study. Patients were stratified by age (6-7, 8-9, and 10-12 year olds) and were dosed with 18...
December 12, 2016: Journal of Child and Adolescent Psychopharmacology
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
#9
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
#10
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
#11
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
#12
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
#13
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 15, 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
#14
REVIEW
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
#15
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
#16
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...
November 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27538886/psychosis-associated-with-acute-recreational-drug-toxicity-a-european-case-series
#17
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
#18
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
#19
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
#20
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
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