List of Depression Spirits for MD Abuse of All Types, Child Abuse
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Antinociceptive Effects of Monoamine Reuptake Inhibitors in Assays of Pain-Stimulated and Pain-Depressed Behaviors
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2012 Antinociceptive Effects of Monoamine Reuptake Inhibitors in Assays of Pain-Stimulated and Pain-Depressed Behaviors Marisa Rosenberg Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Medical Pharmacology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2715 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. ANTINOCICEPTIVE EFFECTS OF MONOAMINE REUPTAKE INHIBITORS IN ASSAYS OF PAIN-STIMULATED AND PAIN-DEPRESSED BEHAVIOR A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University By Marisa B. Rosenberg Bachelor of Science, Temple University, 2008 Advisor: Sidney Stevens Negus, Ph.D. Professor, Department of Pharmacology/Toxicology Virginia Commonwealth University Richmond, VA May, 2012 Acknowledgement First and foremost, I’d like to thank my advisor Dr. Steven Negus, whose unwavering support, guidance and patience throughout my graduate career has helped me become the scientist I am today. His dedication to education, learning and the scientific process has instilled in me a quest for knowledge that I will continue to pursue in life. His thoroughness, attention to detail and understanding of pharmacology has been exemplary to a young person like me just starting out in the field of science. I’d also like to thank all of my committee members (Drs. -
Dopamine Reuptake Transporter (DAT) “Inverse Agonism” E Anovel 66 2 67 3 Hypothesis to Explain the Enigmatic Pharmacology of Cocaine 68 4 * 69 5 Q5 David J
NP5526_proof ■ 24 June 2014 ■ 1/22 Neuropharmacology xxx (2014) 1e22 55 Contents lists available at ScienceDirect 56 57 Neuropharmacology 58 59 60 journal homepage: www.elsevier.com/locate/neuropharm 61 62 63 64 65 1 Dopamine reuptake transporter (DAT) “inverse agonism” e Anovel 66 2 67 3 hypothesis to explain the enigmatic pharmacology of cocaine 68 4 * 69 5 Q5 David J. Heal , Jane Gosden, Sharon L. Smith 70 6 71 RenaSci Limited, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK 7 72 8 73 9 article info abstract 74 10 75 11 76 Article history: The long held view is cocaine's pharmacological effects are mediated by monoamine reuptake inhibition. 12 Available online xxx However, drugs with rapid brain penetration like sibutramine, bupropion, mazindol and tesofensine, 77 13 which are equal to or more potent than cocaine as dopamine reuptake inhibitors, produce no discernable 78 14 Keywords: subjective effects such as drug “highs” or euphoria in drug-experienced human volunteers. Moreover 79 15 Cocaine they are dysphoric and aversive when given at high doses. In vivo experiments in animals demonstrate 80 16 Dopamine reuptake inhibitor that cocaine's monoaminergic pharmacology is profoundly different from that of other prescribed 81 Dopamine releasing agent 17 monoamine reuptake inhibitors, with the exception of methylphenidate. These findings led us to 82 Dopamine transporter fi 18 Inverse agonist conclude that the highly unusual, stimulant pro le of cocaine and related compounds, eg methylphe- 83 19 DAT inverse agonist nidate, is not mediated by monoamine reuptake inhibition alone. 84 We describe the experimental findings which suggest cocaine serves as a negative allosteric 20 Novel mechanism 85 21 modulator to alter the function of the dopamine reuptake transporter (DAT) and reverse its direction of fi 86 22 transport. -
Withdrawing Benzodiazepines in Primary Care
PC\/ICU/ ADTiriC • CNS Drugs 2009,-23(1): 19-34 KtVltW MKIIWLC 1172-7047/I»/O(X)1«119/S4W5/C1 © 2009 Adis Dato Intocmation BV. All rights reserved. Withdrawing Benzodiazepines in Primary Care Malcolm Luder} Andre Tylee^ and ]ohn Donoghue^ 1 Institute of Psychiatry, King's College London, London, England 2 John Moores University, Liverpool, Scotland Contents Abstract ' 19 1. Benzodiazepine Usage 22 2. Interventions 23 2.1 Simple interventions 23 2.2 Piiarmacoiogicai interventions 25 2.3 Psychoiogical Interventions 26 2.4 Meta-Anaiysis ot Various interventions 27 3. Outcomes 28 4. Practicai Issues 29 5. Otiier Medications 30 5.1 Antidepressants 30 5.2 Symptomatic Treatments 30 6. Conciusions 31 Abstract The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. The adverse effects of these drugs have been extensively documented and their effectiveness is being increasingly questioned. Discontinua- tion is usually beneficial as it is followed by improved psychomotor and cognitive functioning, particularly in the elderly. The potential for dependence and addic- tion have also become more apparent. The licensing of SSRIs for anxiety disorders has widened the prescdbers' therapeutic choices (although this group of medications also have their own adverse effects). Melatonin agonists show promise in some forms of insomnia. Accordingly, it is now even more imperative that long-term benzodiazepine users be reviewed with respect to possible discon- tinuation. Strategies for discontinuation start with primary-care practitioners, who are still the main prescdbers. -
(19) United States (12) Patent Application Publication (10) Pub
US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist. -
Strategisk Regnskabsanalyse Og Værdiansættelse Af H. Lundbeck A/S
Copenhagen Business School Hovedopgave 2011 Institut for Regnskab HD-R (Regnskab og og Revision Økonomistyring) Strategisk regnskabsanalyse og værdiansættelse af H. Lundbeck A/S Vejleder: Udarbejdet af: Ole Sørensen Mikael Thaarup Robertsen Institut for Regnskab og Revision Cpr. nr. 300880-XXXX Copenhagen Business School Afleveret 16. maj 2011 EXECUTIVE SUMMARY H. Lundbeck A/S is an international pharmaceutical company focused on development and marketing of treatment for diseases within the central nerve system (CNS). Lundbeck has in the last few years had an outstanding financial performance, but in the same period the value of the company’s stock are at a historical low. On top of that the largest Nordic bank Nordea had a sell recommendation and a target price of 85 DKK as late as end of 2010. Has the sell recommendation and the low target price a justification due to the fact that Lundbeck’s blockbuster product Cipralex®/Lexapro® will lose patent protection in 2012 in the US and 2014 in the remaining of the world? The derived objective of the thesis has been to create a reliable valuation of Lundbeck taking into account the current business, including products and research pipeline, the historic financial performance and the financial outlook for the future. The objective of the strategic analysis has been to obtain the required knowledge about the business, the industry and the society that all influence the future growth scenario. The conclusion on this underlying strategic analysis was that the industry is under pressure from both public health service providers and generic competitors. At the same time the potential marked for CNS products is increasing due to demographic changes and increasing income levels in more recent developed countries. -
Compositions and Methods for Selective Delivery of Oligonucleotide Molecules to Specific Neuron Types
(19) TZZ ¥Z_T (11) EP 2 380 595 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 26.10.2011 Bulletin 2011/43 A61K 47/48 (2006.01) C12N 15/11 (2006.01) A61P 25/00 (2006.01) A61K 49/00 (2006.01) (2006.01) (21) Application number: 10382087.4 A61K 51/00 (22) Date of filing: 19.04.2010 (84) Designated Contracting States: • Alvarado Urbina, Gabriel AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Nepean Ontario K2G 4Z1 (CA) HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL • Bortolozzi Biassoni, Analia Alejandra PT RO SE SI SK SM TR E-08036, Barcelona (ES) Designated Extension States: • Artigas Perez, Francesc AL BA ME RS E-08036, Barcelona (ES) • Vila Bover, Miquel (71) Applicant: Nlife Therapeutics S.L. 15006 La Coruna (ES) E-08035, Barcelona (ES) (72) Inventors: (74) Representative: ABG Patentes, S.L. • Montefeltro, Andrés Pablo Avenida de Burgos 16D E-08014, Barcelon (ES) Edificio Euromor 28036 Madrid (ES) (54) Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types (57) The invention provides a conjugate comprising nucleuc acid toi cell of interests and thus, for the treat- (i) a nucleic acid which is complementary to a target nu- ment of diseases which require a down-regulation of the cleic acid sequence and which expression prevents or protein encoded by the target nucleic acid as well as for reduces expression of the target nucleic acid and (ii) a the delivery of contrast agents to the cells for diagnostic selectivity agent which is capable of binding with high purposes. -
The Role of A6 Subunit-Containing GABAA Receptors in Behavioral
OLGA Yu VEKOVISCHEVA The Role of a6 Subunit-containing GABA Receptors in Behavioral Effects of A Alcohol and Drug Treatments ACADEMIC DISSERTATION To be presented, with the permission of the Faculty of Medicine of the University of Tampere, for public discussion in the auditorium of Tampere School of Public Health, Medisiinarinkatu 3, Tampere, on May 23rd, 2003, at 12 oclock Acta Universitatis Tamperensis 928 University of Tampere Tampere 2003 ACADEMIC DISSERTATION University of Tampere, Medical School University of Turku, Department of Pharmacology and Clinical Pharmacology Finland Supervised by Reviewed by Professor Esa R& Korpi Professor Sture Liljequist University of Helsinki Karolinska Institutet Docent Mikko Uusi-Oukari Docent Tomi Taira University of Turku University of Helsinki Professor Simo Oja University of Tampere Distribution University of Tampere Bookshop TAJU Tel +358 3 215 6055 PO Box 617 Fax +358 3 215 7685 33014 University of Tampere taju@utafi Finland http://granumutafi Cover design by Juha Siro Printed dissertation Electronic dissertation Acta Universitatis Tamperensis 928 Acta Electronica Universitatis Tamperensis 251 ISBN 951-44-5662-9 ISBN 951-44-5663-7 ISSN 1455-1616 ISSN 1456-954X http://actautafi Tampereen yliopistopaino Oy Juvenes Print Tampere 2003 3 CONTENTS CONTENTS 4 LIST OF ORIGINAL PUBLICATIONS 6 ABBREVIATIONS 7 ABSTRACT 8 1. INTRODUCTION 9 2. REVIEW OF THE LITERATURE 11 2.1. The inhibitory γ-aminobutyric acid system. General overview 11 2.2. GABAA receptors 12 2.2.1. Molecular biology of GABAA receptors 12 2.2.2. Diazepam as a classical benzodiazepine modulator of 14 GABAA receptors 2.2.3. Ethanol as a modulator of GABAA receptor function 15 2.3. -
Study of CNS Depressant and Behavioral Effects of Cyclopyrrolone Compound Zopiclone in Different Animal Models
id10341328 pdfMachine by Broadgun Software - a great PDF writer! - a great PDF creator! - http://www.pdfmachine.com http://www.broadgun.com ISSN : 0974 - 7532 Volume 4 Issue 4 Research & Reviews in Trade Science Inc. BBiiooSScciieenncceess Regular Paper RRBS, 4(4), 2010 [173-176] Study of CNS depressant and behavioral effects of cyclopyrrolone compound zopiclone in different animal models Uma A.Bhosale*1, Anand A.Bhosale2 1Dept. of Pharmacology SKNMC, Narhe (Ambegaon) Pune-41, (INDIA) 2Dept. of Pathology SKNMC, Narhe (Ambegaon) Pune-41, (INDIA) E-mail : [email protected] Received: 10th September, 2010 ; Accepted: 20th September, 2010 ABSTRACT KEYWORDS Objectives: To evaluate CNS depressant and behavioral effects of zopiclone Incline plane; in comparison with BZD (lorazepam) by using different animal models. Pentobarbitone Methods: Pharmacological assays used for evaluating CNS Depressant sleeping time; activity are righting reflex test, pentobarbitone sleeping time potentiation, Rota rod apparatus; Rota rod apparatus and Incline plane performance test in albino mice. Open Zopiclone. field apparatus (OFT) was used to study behavioral effects. Data analyzed ’s unpaired-‘t’ test and p<0.05 considered significant. by student Results: Zopiclone (7.5mg/kg p.o.) did not inhibit the Righting reflex however sig- nificant (p<0.001) potentiation of Pentobarbitone sleeping time and de- creased fall off time in Rota rod as well as inclined plane test (P<0.05, P<0.02 respectively) were observed. In OFT increased in exploration (P<0.001) suggestive of anxiolysis was observed. Conclusions: Zopiclone (7.5mg/kg p.o.) has weak CNS Depressant activity and more selective behavioral activity compared to BZDs. -
Benzodiazepine Withdrawal - Does This Lead to an Increase in the Use of Antipsychotics?
The Open Drug Safety Journal, 2012, 3, 1-6 1 Open Access Benzodiazepine Withdrawal - Does This Lead to an Increase in the Use of Antipsychotics? Viggo Rask Kragh Jørgensen* Lægehuset Thyborøn, Ærøvej 1b, 7680 Thyborøn, Denmark Abstract: Introduction: In 2004, two Danish GPs in the town of Thyborøn introduced a more restrictive approach to the prescription of benzodiazepines (BD) and cyclopyrrolones (CP). A prescription could only be renewed following personal consultation, and medication could only be prescribed for one month at a time. Every month, the practitioner and the pa- tient had to consider whether current levels of consumption were appropriate or whether a reduction was to be imple- mented. This approach reduced the consumption of anxiolytics and hypnotics by 87% and 92%, respectively, over a 3- year period. There is a general paucity of knowledge as to whether an intervention such as the one described above actu- ally reduces drug consumption, or merely transfers consumption to other drugs, where especially antipsychotics (AP) are in the spotlight. Materials and Methods: The current article describes the consumption of AP before and after the intervention. Consump- tion was followed via the Danish Medicines Agency's website Ordiprax, where one can determine the amount of prescrip- tion medications sold in pharmacies by individual medical practices. Results: In both practices, a non-significant increase in the overall consumption of AP was observed during the course of the intervention against BD and CP. Although the consumption of some AP subgroups experienced a significant increase, no specific pattern could be observed. Conclusion: The intervention against BD and CP did not result in a significant increase in total prescription volumes of AP. -
Expansion of a Cheminformatic Database of Spectral Data for Forensic Chemists and Toxicologists
The author(s) shown below used Federal funds provided by the U.S. Department of Justice and prepared the following final report: Document Title: Expansion of a Cheminformatic Database of Spectral Data for Forensic Chemists and Toxicologists Author(s): Peter Stout, Katherine Moore, Megan Grabenauer, Jeri Ropero-Miller Document No.: 241444 Date Received: March 2013 Award Number: 2010-DN-BX-K177 This report has not been published by the U.S. Department of Justice. To provide better customer service, NCJRS has made this Federally- funded grant report available electronically. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Award Number: 2010-DN-BX-K177 July 16, 2012 Expansion of a Cheminformatic Database of Spectral Data for Forensic Chemists and Toxicologists Final Report Authors: Peter Stout Katherine Moore Megan Grabenauer Jeri Ropero-Miller This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Expansion of a Cheminformatic Database of Spectral Data for Forensic Chemists and Toxicologists Table of Contents Abstract ........................................................................................................................................... 1 Executive Summary ....................................................................................................................... -
Affinity of Compounds for the Benzodiazepine Site (Neurotransmitter/Mutagenesis/Channel/Inhibitory) DOLAN B
Proc. Nati. Acad. Sci. USA Vol. 88, pp. 1421-1425, February 1991 Neurobiology y-Aminobutyric acid type A receptor point mutation increases the affinity of compounds for the benzodiazepine site (neurotransmitter/mutagenesis/channel/inhibitory) DOLAN B. PRITCHETT*tt AND PETER H. SEEBURGt *Departments of Pediatrics and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104; and tLaboratory of Molecular Neuroendocrinology, Center for Molecular Biology, University of Heidelberg, 6900 Heidelberg, Federal Republic of Germany Communicated by Erminio Costa, November 13, 1990 ABSTRACT Recombinantly expressed y-aminobutyric benzodiazepine agonists. The a, subunit imparts high-affinity acid type A (GABAA) receptors consisting of a,, P2, and 72 binding for CL 218872 (15, 19), while a2, a3, and a5 subunits subunits contain a binding site for benzodiazepines that differs create sites with 10-fold lower affinities for this triazolopy- in its properties from that of ac3%2y2 receptors. Amino acid ridozine (8, 15). Several other compounds, including the substitutions between the GABAA receptor a subunits were benzodiazepines quazepam and 2-oxoquazepam (20), the analyzed for their effect on the binding of compounds to the f3-carbolines f8-CCM and 3-CCE (21), and the imidazolpy- benzodiazepine site. By converting ever smaller regions of the ridines zolpidem, alpidem, and AHR-14479 (22, 23) show a3 subunit sequence to that of the a, subunit, we show that a similar pharmacological profiles, with the notable exception single substitution (glycine for glutamic acidj increases the that the three last-named compounds fail to bind to ternary affinity for several compounds approximately 10-fold without receptors containing the a5 subunit (8). -
Director's Report 2/01
Director's Report 2/01 Director's Report to the National Advisory Council on Drug Abuse February, 2001 Index Research Findings Basic Research Behavioral Research Treatment Research and Development Research on AIDS and Other Medical Consequences of Drug Abuse Epidemiology, Etiology and Prevention Research Services Research Intramural Research Program Activities Extramural Policy and Review Activities Congressional Affairs International Activities Meetings and Conferences Media and Education Activities Planned Meetings Publications Staff Highlights Grantee Honors [Office of Director] [First Report Section] Archive Home | Accessibility | Privacy | FOIA (NIH) | Current NIDA Home Page The National Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , a component of the U.S. Department of Health and Human Services. Questions? _ See our Contact Information. https://archives.drugabuse.gov/DirReports/DirRep201/DirectorRepIndex.html[11/17/16, 9:48:57 PM] Director's Report 2/01 - Basic Research Director's Report to the National Advisory Council on Drug Abuse February, 2001 Research Findings Basic Research Role for GDNF in Biochemical and Behavioral Adaptations to Drugs of Abuse Drs. David Russell and Eric Nestler and their research team at the Yale University examined a role for Glial-Derived Neurotrophic Factor (GDNF) in adaptations to drugs of abuse. Infusion of GDNF into the ventral tegmental area (VTA), a dopaminergic brain region important for addiction, blocks certain biochemical adaptations to chronic cocaine or morphine as well as the rewarding effects of cocaine. Conversely, responses to cocaine are enhanced in rats by intra-VTA infusion of an anti-GDNF antibody and in mice heterozygous for a null mutation in the GDNF gene.