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James Ermer, Mary Corcoran, Kenneth Lasseter, Patrick T Martin
BACKGROUND: This open-label, crossover study examined lisdexamfetamine dimesylate (LDX) and d-amphetamine pharmacokinetics in healthy adults after administration of an intact LDX capsule or after the capsule was emptied into orange juice or yogurt and the contents consumed. METHODS: Healthy adult volunteers (N = 30) were administered a 70-mg LDX capsule or the contents of a 70-mg capsule mixed with yogurt or orange juice using a three-way crossover design. Blood samples were collected serially for up to 96 h postdose...
September 20, 2016: Therapeutic Drug Monitoring
Martin H Zack, Daniela S Lobo, Candice Biback, Tim Fang, Kelly Smart, Daniel Tatone, Aditi Kalia, Daniel Digiacomo, James L Kennedy
This study investigated the role of dopamine, and specifically the D1 receptor (D1R), in the reinforcing effects of a slot-machine game in healthy volunteers (n=30). To compare gambling and drug effects, subjects received the prototypic psychostimulant drug d-amphetamine (AMPH; 20 mg) in a multi-session, placebo-controlled design. To isolate D1R, half the subjects were pretreated with the preferential D2 receptor antagonist haloperidol (HAL; 3 mg), and the other half with the mixed D1-D2 antagonist fluphenazine (FLU; 3 mg) before the game (Phase I) and AMPH (Phase II)...
September 13, 2016: Journal of Psychopharmacology
Melike Sever, Mesut Turkyilmaz, Cansu Sevinc, Aysen Cakir, Busra Ocalan, Mehmet Cansev, Mustafa O Guler, Ayse B Tekinay
Parkinson's Disease (PD) is characterized by progressive degeneration of dopaminergic nigrostriatal neurons and reduction in striatal dopamine levels. Although there are few treatment options for PD such as Levodopa, they are used just to relieve and modify the symptoms. There are no therapies available for PD to slow down the degeneration process in the brain and recover the lost function. In this study, we used extracellular matrix (ECM) mimetic peptide amphiphile (PA) nanofibers as a potential therapeutic approach in a PD rat model...
September 9, 2016: Acta Biomaterialia
Blake A Hutsell, S Stevens Negus, Matthew L Banks
BACKGROUND: Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined...
September 5, 2016: Drug and Alcohol Dependence
Chloe J Jordan, Carley Lemay, Linda P Dwoskin, Kathleen M Kantak
RATIONALE: Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adolescents remain controversial with respect to later development of cocaine abuse. Past research demonstrated that adolescent methylphenidate treatment increased several aspects of cocaine self-administration during adulthood using the spontaneously hypertensive rat (SHR) model of ADHD. Presently, we determined effects of the alternate stimulant medication, d-amphetamine, on cocaine self-administration...
September 6, 2016: Psychopharmacology
Eloisa Comiran, Fabiano Barreto, Leonardo Z Meneghini, Graciela Carlos, Pedro E Fröehlich, Renata Pereira Limberger
Lisdexamfetamine (LDX) is a long-acting prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder and binge-eating disorder symptoms. In vivo hydrolysis of LDX amide bond releases the therapeutically active d-amphetamine (d-AMPH). Since toxicological tests in biological samples can detect AMPH due to the use of some medications, efficient methods are needed in order to correctly interpret the results. The aim of this study was to develop and validate a LC-MS/MS method for the simultaneous quantification of LDX and its main biotransformation product AMPH in human oral fluid, plasma and urine...
August 12, 2016: Biomedical Chromatography: BMC
Adem Can, Douglas O Frost, Roger Cachope, Joseph F Cheer, Todd D Gould
Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium...
August 11, 2016: Journal of Neurochemistry
Christopher A Krebs, William J Reilly, Karen G Anderson
Impulsive choice in humans can be altered by changing reinforcer magnitude; however, this effect has not been found in rats. Current levels of impulsive choice can also influence effects of d-amphetamine. This study used a within-subject assessment to determine if impulsive choice is sensitive to changes in reinforcer magnitude, and whether effects of d-amphetamine are related to current levels of impulsive choice. A discounting procedure in which choice was for a smaller reinforcer available immediately or a larger reinforcer available after a delay that increased within session was used...
September 2016: Behavioural Processes
Rubén García-Cabrerizo, M Julia García-Fuster
The aim of this study was to compare the effects of amphetamine-like psychostimulant drugs (i.e., MDMA, methamphetamine, D-amphetamine) on rat hippocampal cell genesis at different developmental ages (i.e., early adolescence vs. young adulthood) to determine if there were periods of vulnerability to drug-induced brain changes. Although adolescence is a period of great vulnerability to the neurochemical effects of specific drugs of abuse, several reports suggest that adult rats are more susceptible than adolescents to the negative effects of these drugs...
June 29, 2016: Neurotoxicology
Kelly E Wood, Matthew D Krasowski
INTRODUCTION: Stimulant medications are approved to treat attention deficit hyperactivity disorder (ADHD) in children over the age of 6 years. Fatal ingestion of stimulants by children has been reported, although most ingestions do not result in severe toxicity. Lisdexamfetamine dimesylate, a once daily long-acting stimulant, is a prodrug requiring conversion to its active form, dextroamphetamine, in the bloodstream. Based on its unique pharmacokinetics, peak levels of d-amphetamine are delayed...
June 8, 2016: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
Emma Childs, Anya K Bershad, Harriet de Wit
Psychostimulant drugs alter the salience of stimuli in both laboratory animals and humans. In animals, stimulants increase rates of responding to conditioned incentive stimuli, and in humans, amphetamine increases positive ratings of emotional images. However, the effects of stimulants on real-life emotional events have not been studied in humans. In this study, we examined the effect of d-amphetamine on responses to acute psychosocial stress using a public speaking task. Healthy volunteers (N=56) participated in two experimental sessions, one with a psychosocial stressor (the Trier Social Stress Test) and one with a non-stressful control task...
July 2016: Journal of Psychopharmacology
Henrik H Hansen, Katrine Fabricius, Pernille Barkholt, Jens D Mikkelsen, Jacob Jelsing, Charles Pyke, Lotte Bjerre Knudsen, Niels Vrang
Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, have been demonstrated to promote neuroprotection in the rat 6-hydroxydopamine (6-OHDA) neurotoxin model of Parkinson's disease (PD), a neurodegenerative disorder characterized by progressive nigrostriatal dopaminergic neuron loss. In this report, we characterized the effect of a long-acting GLP-1 receptor agonist, liraglutide (500µg/kg/day, s.c.) in the context of a partial or advanced (full) 6-OHDA induced nigral lesion in the rat. Rats received a low (3µg, partial lesion) or high (13...
September 1, 2016: Brain Research
Herbert M Himmel, Michael Hoffmann
INTRODUCTION: Compound X is a new proprietary antihypertensive agent that induces its pharmacodynamic effect at an approximate plasma Cmax.u of 0.6nmol/L (rat hypertension model). However, Compound X also shows potent off-target activity at PDE-10a (IC50~12nmol/L). Since PDE-10a is expressed predominantly in brain (striatum) and inhibition/knockout of PDE-10a have been reported to result in anti-psychotic effects, we have established the "induced hyperactivity" test for CNS de-risking of Compound X...
September 2016: Journal of Pharmacological and Toxicological Methods
Christopher T Smith, Linh C Dang, Ronald L Cowan, Robert M Kessler, David H Zald
Subjective responses to psychostimulants vary, the basis of which is poorly understood, especially in relation to possible cortical contributions. Here, we tested for relationships between participants' positive subjective responses to oral d-amphetamine (dAMPH) versus placebo and variability in striatal and extrastriatal dopamine (DA) receptor availability and release, measured via positron emission tomography (PET) with the radiotracer (18)F-fallypride. Analyses focused on 35 healthy adult participants showing positive subjective effects to dAMPH measured via the Drug Effects Questionnaire (DEQ) Feel, Like, High, and Want More subscales (Responders), and were repeated after inclusion of 11 subjects who lacked subjective responses...
September 2016: Neuropharmacology
David J Heal, Simon Goddard, Richard J Brammer, Peter H Hutson, Steven P Vickers
Compulsive and perseverative behaviour in binge-eating, female, Wistar rats was investigated in a novel food reward/punished responding conflict model. Rats were trained to perform the conditioned avoidance response task. When proficient, the paradigm was altered to a food-associated conflict test by placing a chocolate-filled jar (empty jar for controls) in one compartment of the shuttle box. Entry into the compartment with the jar triggered the conditioning stimulus after a variable interval, and foot-shock 10 seconds later if the rat did not leave...
July 2016: Journal of Psychopharmacology
Li-Li Zhang, Hong-Qi Liu, Xu-Hong Yu, Ying Zhang, Jia-Sheng Tian, Xu-Rui Song, Bing Han, Ai-Jun Liu
BACKGROUND AND AIMS: Severe motion sickness is a huge obstacle for people conducting precise aviation, marine or emergency service tasks. The combination of scopolamine and d-amphetamine is most effective in preventing severe motion sickness. However, this combination is not included in any present pharmacopoeia due to the abuse liability of d-amphetamine. We wanted to find a combination to replace it for the treatment of severe motion sickness. METHODS AND RESULTS: We compared the efficacy of scopolamine, diphenhydramine, and granisetron (representing three classes of drugs) with different doses, and found that scopolamine was the most effective one...
August 2016: CNS Neuroscience & Therapeutics
Maria Moscoso-Castro, Irene Gracia-Rubio, Francisco Ciruela, Olga Valverde
Schizophrenia is a chronic severe mental disorder with a presumed neurodevelopmental origin, and no effective treatment. Schizophrenia is a multifactorial disease with genetic, environmental and neurochemical etiology. The main theories on the pathophysiology of this disorder include alterations in dopaminergic and glutamatergic neurotransmission in limbic and cortical areas of the brain. Early hypotheses also suggested that nucleoside adenosine is a putative affected neurotransmitter system, and clinical evidence suggests that adenosine adjuvants improve treatment outcomes, especially in poorly responsive patients...
July 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Eloisa Comiran, Félix Henrique Kessler, Pedro Eduardo Fröehlich, Renata Pereira Limberger
Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) symptoms. The in vivo pharmacodynamics of LDX is the same as that of its active product d-AMPH, although there are a few qualitative and quantitative differences due to pharmacokinetics. Due to the specific pharmacokinetics of the long-acting stimulants, this article revises the pharmacokinetic studies on LDX, the newest amphetamine pro-drug. The Medline/Pubmed, Science Direct and Biblioteca Virtual em Saúde (Lilacs and Ibecs) (2007-2016) databases were searched for articles and their list of references...
June 30, 2016: European Journal of Pharmaceutical Sciences
Stephanie Collins Reed, Suzette M Evans
BACKGROUND: Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor...
June 1, 2016: Drug and Alcohol Dependence
Scott A Wong, Raj Thapa, Cecilia A Badenhorst, Alicia R Briggs, Justan A Sawada, Aaron J Gruber
Amphetamine and other drugs of abuse have both short-term and long-lasting effects on brain function, and drug sensitization paradigms often result in chronic impairments in behavioral flexibility. Here we show that acute amphetamine administration temporarily renders rats less sensitive to reward omission, as revealed by a decrease in lose-shift responding during a binary choice task. Intracerebral infusions of amphetamine into ventral striatum did not affect lose-shift responding but did increase errant behavior in which rats chose to check both reward feeders before beginning the next trial...
April 22, 2016: Neuroscience
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