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https://www.readbyqxmd.com/read/28091572/a-computational-psychiatry-approach-identifies-how-alpha-2a-noradrenergic-agonist-guanfacine-affects-feature-based-reinforcement-learning-in-the-macaque
#1
S A Hassani, M Oemisch, M Balcarras, S Westendorff, S Ardid, M A van der Meer, P Tiesinga, T Womelsdorf
Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073796/comparative-efficacy-and-tolerability-of-pharmacological-interventions-for-attention-deficit-hyperactivity-disorder-in-children-adolescents-and-adults-protocol-for-a-systematic-review-and-network-meta-analysis
#2
Samuele Cortese, Nicoletta Adamo, Christina Mohr-Jensen, Adrian J Hayes, Sahar Bhatti, Sara Carucci, Cinzia Del Giovane, Lauren Z Atkinson, Tobias Banaschewski, Emily Simonoff, Alessandro Zuddas, Corrado Barbui, Marianna Purgato, Hans-Christoph Steinhausen, Farhad Shokraneh, Jun Xia, Andrea Cipriani, David Coghill
INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles...
January 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28063948/cytokine-il-10-activators-of-pi3-kinase-agonists-of-%C3%AE-2-adrenoreceptor-and-antioxidants-prevent-ischemia-induced-cell-death-in-rat-hippocampal-cultures
#3
Egor A Turovsky, Maria V Turovskaya, Sergei G Gaidin, Valery P Zinchenko
In the present work we compared the protective effect of anti-inflammatory cytokine IL-10 with the action of a PI3-kinase selective activator 740 Y-P, selective agonists of alpha-2 adrenoreceptor, guanfacine and UK-14,304, and compounds having antioxidant effect: recombinant human peroxiredoxin 6 and B27, in hippocampal cell culture during OGD (ischemia-like conditions). It has been shown that the response of cells to OGD in the control includes two phases. The first phase was accompanied by an increase in the frequency of spontaneous synchronous Ca(2+)-oscillations (SSCO) in neurons and Ca(2+)-pulse in astrocytes...
January 4, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28028603/guanfacine-alters-the-effect-of-stress-and-smoking-on-heart-rate-variability-in-regular-daily-smokers
#4
Terril L Verplaetse, Philip H Smith, Kathryn M Z Smith, Lindsay M Oberleitner, Sherry A McKee
BACKGROUND: We had previously demonstrated that guanfacine, an α2a-adrenergic agonist, attenuated the effect of stress on smoking-lapse behavior in regular daily smokers. Heart rate variability (HRV), a measure of vagal activity, may be a potential mechanism underlying the relationship between stress, smoking, and relapse. METHODS: We examined whether guanfacine (0 mg/day vs. 3 mg/day; n = 26) altered changes in high-frequency heart rate variability (HF-HRV) following stress and ad-lib smoking using a validated laboratory analogue of smoking-lapse behavior...
December 27, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/28001002/the-effects-of-guanfacine-and-phenylephrine-on-a-spiking-neuron-model-of-working-memory
#5
Peter Duggins, Terrence C Stewart, Xuan Choo, Chris Eliasmith
We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate two drugs that affect WM: guanfacine (GFC) and phenylephrine (PHE). In this model, the loss of information over time results from changes in the spiking neural activity through recurrent connections. We reproduce the standard forgetting curve and then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating functional, neural, and biophysical properties of the model...
December 21, 2016: Topics in Cognitive Science
https://www.readbyqxmd.com/read/27972888/a-cost-effectiveness-analysis-of-guanfacine-extended-release-treatment-in-pediatric-attention-deficit-hyperactivity-disorder
#6
S Maeda, K Shimozuma, Y Takeda
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27828696/current-and-investigational-medication-delivery-systems-for-treating-attention-deficit-hyperactivity-disorder
#7
Rakesh Jain, Alain Katic
OBJECTIVE: To review currently available formulations and emphasize unmet needs in the pharmacologic management of attention-deficit/hyperactivity disorder (ADHD). DATA SOURCES: Publications and clinical trials were identified through PubMed and ClinicalTrials.gov, respectively. A Web-based search identified prescribing information for approved agents for treating ADHD, along with relevant guidelines and diagnostic criteria. STUDY SELECTION: The following search terms were used: (1) ADHD or attention-deficit/hyperactivity disorder or ADD or attention deficit hyperactivity disorder and/or (2) amphetamine or methylphenidate or atomoxetine or guanfacine or clonidine...
August 18, 2016: Primary Care Companion to CNS Disorders
https://www.readbyqxmd.com/read/27738872/an-evaluation-on-the-efficacy-and-safety-of-treatments-for-attention-deficit-hyperactivity-disorder-in-children-and-adolescents-a-comparison-of-multiple-treatments
#8
Ying Li, Jie Gao, Shu He, Yan Zhang, Qiwei Wang
Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders. We carried out this comparison of multiple treatments based on sufficient data in attempt to evaluate the efficacy and safety of ADHD medication for children and adolescents. PubMed, Embase and the Cochrane Database were used to search for relevant articles. Changes in the ADHD Rating Scale (ADHD-RS) scores and the Conners' Parent Rating Scale-Revised (CPRS) scores were used as outcomes for efficacy. Withdrawals due to all-cause, adverse effects and lack of efficacy were defined as primary outcomes evaluating the safety of such medications...
October 13, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27677308/ahr-cyp1a1-interplay-triggers-lymphatic-barrier-breaching-in-breast-cancer-spheroids-by-inducing-12-s-hete-synthesis
#9
Chi Huu Nguyen, Stefan Brenner, Nicole Huttary, Atanas Georgiev Atanasov, Verena Maria Dirsch, Waranya Chatuphonprasert, Sivio Holzner, Serena Stadler, Juliane Riha, Sigurd Krieger, Rainer de Martin, Zsuzsanna Bago-Horvath, Georg Krupitza, Walter Jäger
A causal link between overexpression of aryl hydrocarbon receptor (AHR) and its target cytochrome P450 1A1 (CYP1A1) and metastatic outgrowth of various cancer entities has been established. Nevertheless, the mechanism how AHR/CYP1A1 support metastasis formation is still little understood. In vitro we discovered a potential mechanism facilitating tumour dissemination based on the production of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). Utilising a three-dimensional lymph endothelial cell (LEC) monolayer & MDA-MB231 breast cancer cell spheroid co-culture model in combination with knock-down approach allowed elucidation of the molecular/biochemical basis of AHR/CYP1A1-induced tumour breaching through the LEC barrier...
September 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27669299/vasoactivity-and-vasoconstriction-changes-in-cattle-related-to-time-off-toxic-endophyte-infected-tall-fescue
#10
James L Klotz, Glen E Aiken, Jessica R Bussard, Andrew P Foote, David L Harmon, Ben M Goff, F Neal Schrick, James R Strickland
Previous research has indicated that serotonergic and α-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichlöe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time necessary for the vascular effects of ergot alkaloids to subside. Two experiments were conducted to investigate changes in vascular contractile response and vasoconstriction over time relative to removal from an ergot alkaloid-containing E+ tall fescue pasture...
2016: Toxins
https://www.readbyqxmd.com/read/27620206/evaluating-matching-adjusted-indirect-comparisons-in-practice-a-case-study-of-patients-with-attention-deficit-hyperactivity-disorder
#11
Jason Shafrin, Anshu Shrestha, Amitabh Chandra, M Haim Erder, Vanja Sikirica
Differences in patient characteristics across trials may bias efficacy estimates from indirect treatment comparisons. To address this issue, matching-adjusted indirect comparison (MAIC) measures treatment efficacy after weighting individual patient data to match patient characteristics across trials. To date, however, there is no consensus on how best to implement MAIC. To address this issue, we applied MAIC to measure how two attention-deficit/hyperactivity disorder (ADHD) treatments (guanfacine extended release and atomoxetine hydrochloride) affect patients' ADHD symptoms, as measured by the ADHD Rating Scale IV score...
September 13, 2016: Health Economics
https://www.readbyqxmd.com/read/27509312/pharmacological-investigations-of-a-yohimbine-impulsivity-interaction-in-rats
#12
Megan K Mahoney, John H Barnes, David Wiercigroch, Mary C Olmstead
Both impulsivity and stress are risk factors for substance abuse, but it is not clear how these two processes interact to alter susceptibility for the disorder. The aim of this project was to examine the pharmacology of a stress-impulsivity interaction in rats. To do so, we tested the effects of yohimbine on impulsive action and then assessed whether behavioural changes could be reduced by antagonists at different receptor subtypes. Male Long-Evans rats were injected with various doses of yohimbine (0-5.0 mg/kg) before testing in the response-inhibition task...
October 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27483130/acute-and-long-term-cardiovascular-effects-of-stimulant-guanfacine-and-combination-therapy-for-attention-deficit-hyperactivity-disorder
#13
Gregory R Sayer, James J McGough, Jennifer Levitt, Jennifer Cowen, Alexandra Sturm, Edward Castelo, James T McCracken
OBJECTIVES: This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder. METHODS: Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response...
December 2016: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/27453081/effects-of-d-methylphenidate-guanfacine-and-their-combination-on-electroencephalogram-resting-state-spectral-power-in-attention-deficit-hyperactivity-disorder
#14
Sandra K Loo, Robert M Bilder, Alexander L Cho, Alexandra Sturm, Jennifer Cowen, Patricia Walshaw, Jennifer Levitt, Melissa Del'Homme, John Piacentini, James J McGough, James T McCracken
OBJECTIVE: Psychostimulant medications are the gold standard of treatment for attention-deficit/hyperactivity disorder (ADHD); however, a significant minority (∼30%) of individuals with ADHD fail to respond favorably. Noradrenergic agents are increasingly used as ADHD monotherapies or adjuncts for suboptimal stimulant response, yet knowledge of their cortical effects is limited. This study is the first to examine comparative effects of guanfacine (an α adrenergic 2A agonist), psychostimulant, and their combination on resting state cortical activity in ADHD...
August 2016: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/27453080/cognitive-effects-of-stimulant-guanfacine-and-combined%C3%A2-treatment-in-child-and-adolescent-attention-deficit-hyperactivity-disorder
#15
Robert M Bilder, Sandra K Loo, James J McGough, Fiona Whelan, Gerhard Hellemann, Catherine Sugar, Melissa Del'Homme, Alexandra Sturm, Jennifer Cowen, Grant Hanada, James T McCracken
OBJECTIVE: Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. METHOD: Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB)...
August 2016: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/27453079/combined-stimulant-and-guanfacine-administration-in-attention-deficit-hyperactivity-disorder-a-controlled-comparative-study
#16
James T McCracken, James J McGough, Sandra K Loo, Jennifer Levitt, Melissa Del'Homme, Jennifer Cowen, Alexandra Sturm, Fiona Whelan, Gerhard Hellemann, Catherine Sugar, Robert M Bilder
OBJECTIVE: Because models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses. This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH) with guanfacine (GUAN), an α2A receptor agonist, would be clinically superior to either monotherapy and would have equal tolerability...
August 2016: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/27384184/alpha-2a-adrenoceptor-agonist-guanfacine-restores-diuretic-efficiency-in-experimental-cirrhotic-ascites-comparison-with-clonidine
#17
Giovanni Sansoè, Manuela Aragno, Raffaella Mastrocola, Giulio Mengozzi, Maurizio Parola
BACKGROUND: In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites. AIM: To compare clonidine (aspecific α2-adrenoceptor agonist) to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist), both associated with diuretics, in experimental cirrhotic ascites. METHODS AND RESULTS: Six groups of 12 rats were studied: controls (G1); controls receiving furosemide and potassium canrenoate (G2); rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3); cirrhotic rats treated (over the 11th-14th CCl4 weeks) with furosemide and canrenoate (G4), furosemide, canrenoate and clonidine (G5), or diuretics and SSP002021R (G6)...
2016: PloS One
https://www.readbyqxmd.com/read/27357497/sleep-problems-in-children-with-attention-deficit-hyperactivity-disorder-current-status-of-knowledge-and-appropriate-management
#18
REVIEW
Ming-Horng Tsai, Jen-Fu Hsu, Yu-Shu Huang
Attention deficit hyperactivity disorder (ADHD) affects approximately 5 % of children and adolescents, and sleep problems are common in these patients. There is growing evidence informing the significant importance of sleep problems in youth with ADHD. The sleep problems in children with ADHD include specific sleep disorders and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. The specific sleep disorders of ADHD children include behaviorally based insomnia, sleep-disordered breathing, and restless legs syndrome/periodic limb movement disorder...
August 2016: Current Psychiatry Reports
https://www.readbyqxmd.com/read/27254403/mechanism-of-action-of-guanfacine-a-postsynaptic-differential-approach-to-the-treatment-of-attention-deficit-hyperactivity-disorder-adhd
#19
Cecilio Alamo, Francisco López-Muñoz, Javier Sánchez-García
The treatment of ADHD has focused on the use of psychostimulants drugs such as methylphenidate or amphetamine and derivatives, or not stimulants agents, such as atomoxetine. These agents act mainly on catecholaminergic presynaptic mechanisms. Recently the European Medicines Agency (EMA) has approved another not psychostimulant drug, guanfacine extended release (ER), as a new option to the treatment of ADHD, which acts at postsynaptic level. Guanfacine stimulates postsynaptic alfa-2A adrenergic receptors so it inhibits the production of cAMP and closes HCN channels enhancing the effectiveness of the signal of the pyramidal neurons of the prefrontal cortex (PFC), thus improving working memory and attention...
May 2016: Actas Españolas de Psiquiatría
https://www.readbyqxmd.com/read/27236168/treating-adhd-in-prison-focus-on-alpha-2-agonists-clonidine-and-guanfacine
#20
Jeffrey A Mattes
Attention deficit/hyperactivity disorder (ADHD) is prevalent in prison populations, but optimal treatment recommendations in prison are uncertain. Stimulants are problematic because of the potential for abuse. This article is a review of medication options for ADHD, focusing on the α2 agonists clonidine and guanfacine, which, in their extended-release (ER) forms, are U.S. Food and Drug Administration (FDA) approved for the treatment of ADHD, although they are probably less efficacious, overall, than stimulants...
June 2016: Journal of the American Academy of Psychiatry and the Law
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