DOCSLIB.ORG

Drug Discrimination: Applications to Drug Abuse Research

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Drug Discrimination: Applications to Drug Abuse Research 116 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Drug Discrimination: Applications to Drug Abuse Research Editors: Richard A. Glennon, Ph.D. Medical College of Virginia Virginia Commonwealth University Torbjörn U.C. Järbe, Ph.D. Department of Psychology University of Uppsala Jerry Frankenheim, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Research Monograph 116 1991 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGMENT This monograph is based on the papers from the “International Drug Discrimination Symposium” held from June 25 to June 27, 1990, in Noordwijkerhout, The Netherlands. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the US. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names appearing in this publication are used only because they are considered essential in the context of the studies reported herein. NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of American Statistics Index, Biosciences information Service, Chemical Abstracts, Current Contents, Psychological Abstracts, and Psychopharmacology Abstracts. DHHS publication number (ADM)92-1878 Printed 1991 ii Contents Introduction . .1 Richard A. Glennon A Historical Perspective on Drug Discrimination . .5 Donald A. Overton Discriminative Stimulus Properties of Hallucinogens and Related Designer Drugs . 25 Richard A. Glennon Discriminative Stimulus Properties of Amphetamine, Cathinone, and Related Agents . 45 A.J. Goudie Discriminative Stimulus Effects of Cocaine . .61 William L. Woolverton Discriminative Stimulus Functions of Cannabinoids/Cannabimimetics . .75 Torbjörn U.C. Järbe and Diane A. Mathis Discriminative Stimulus Properties of Nicotine: Mechanisms of Transduction . .101 John A. Rosecrans and Heidi F. Villanueva Discriminative Stimulus Properties of Benzodiazepines and Several New Anxiolytics . 117 Richard Young iii Distinctive Discriminative Effects of Ethanol . 131 Herbert Barry III Training Dose: Influences in Opioid Drug Discrimination . 145 Sandra D. Comer, Charles P. France, and James H. Woods Discriminative Stimulus Properties of Phencyclidine and Other NMDA Antagonists . 163 Robert L. Balster Discriminative Stimulus Effects of Psychomotor Stimulants and Benzodiazepines in Humans . 181 Chris-Ellyn Johanson Tolerance to Drugs Acting as Discriminative Stimuli . 197 Alice M. Young Tolerance: Role of Conditioning Processes . 213 Shepard Siegel Responding to Drug-Related Stimuli in Humans as a Function of Drug-Use History . 231 Ronald N. Ehrman, Steven J. Robbins, Anna Rose Childress, A. Thomas McLellan. and Charles P. O’Brien State Dependency as a Mechanism of Central Nervous System Drug Action . 245 Francis C. Colpaert State-Dependent Learning With Social Drugs . 267 Geoff Lowe Discriminative Stimulus Effects of Drug Mixtures in Rats . 277 I.P. Stolerman, E.A. Mariathasan, and H. S. Garcha iv Application of Drug Discrimination With Drugs of Abuse To Develop New Therapeutic Agents . 307 Theo Frans Meert Intracranial Stimulation as Reinforcer for Neuropeptide Discrimination . 325 Muriel Gewiss, Christian Heidbreder, and Philippe De Witte Drug Discrimination Used To Study Drug Withdrawal . 337 M. W. Emmett-Oglesby and G.A. Rowan Schedule-Induced Self-Injection of Drugs . 359 George Singer Use of Drug Discrimination in Drug Abuse Research . 369 James B. Appel, Lisa E. Baker, Rita L. Barrett, Julie Broadbent, Elizabeth M. Michael, Elizabeth E. Riddle, and Bette J. Van Groll Symposium Critique . 399 L.S. Harris v For sale by the U.S. Government Printing Office Superintendent of Documents, Mail Stop: SSOP, Washington, DC 20402-9328 ISBN 0-16-036035-8 Introduction Richard A. Glennon The drug discrimination (DD) paradigm is essentially a drug detection procedure whereby animals are trained to recognize or discriminate the stimulus effects of a given dose of a particular training drug from those of (1) a different dose of the same training drug, (2) a different training drug, or, more commonly, (3) saline/vehicle (i.e., a nondrug condition). The most commonly employed apparatus for conducting drug discrimination studies is a two-lever operant chamber; however, several other types of test procedures, including three-lever chambers, are also being used. Several species of animals are quite popular, primarily rat, pigeon, and monkey; the use of other species, including human, is now becoming more common. The DD paradigm, by itself, cannot be used to completely characterize a novel agent. This is true of any pharmacological procedure. However, the DD paradigm can be used to investigate a wide variety of pharmacological aspects relating to the stimulus properties of a drug. These aspects include, for example, time of onset and duration of action, mechanism of action, similarity of effect to other agents, structure-activity relationships, activity of metabolites, and identification and development of potential antagonists. Recently, the paradigm has been used to investigate the processes of tolerance and withdrawal. There have already been several international drug discrimination symposia. For the most part, these symposia were concerned more with the technique itself than with the application of the technique for the investigation of a particular problem. Prior emphasis has been on, for example, the use of drug discrimination in central nervous system pharmacology and on the transduction mechanisms involved in the stimulus effects of drugs. Because many of the drugs used in DD studies have a potential for abuse or, indeed, are already noted for their abuse, we felt the time was right to address the application of DD in drug abuse research. 1 This monograph presents selected papers from the 1990 International Drug Discrimination Symposium held in Noordwijkerhout, The Netherlands, June 25-27,1990. The symposium was cosponsored by the European Behavioral Pharmacology Society and the Society for the Stimulus Properties of Drugs. The theme for the 1990 symposium was “Drug Discrimination: Applications in Drug Abuse Research.” The meeting consisted of a number of invited presentations on drug abuse research; it was also open to a general poster session. Abstracts for most of the presentations were published as a supplement to Psychopharmacology volume 101,1990. Unlike previous symposia, this meeting brought together members of the international academic, industrial, government, and drug enforcement communities to discuss the relevance and application of the paradigm to a single health-related issue: drug abuse. Presentations ranged from the basic science, such as mechanisms of action and structure-activity relationships, to DD studies involving human subjects, to the role of DD in the legal control of abused substances. Another topic of interest was the use of abused substances as training drugs for developing new therapeutic agents. The consensus of the symposium participants was that the DD paradigm is an important, useful, and very versatile tool for investigating drugs of abuse. However, the committee invited several speakers to address this issue in a formal sense. A separate session devoted to this topic was entitled “Invited Perspectives.” The committee selected a member of the U.S. Drug Enforcement Administration (Dr. F. Sapienza) to address the issue from a law enforcement perspective. Two additional speakers were also requested to critique the DD paradigm and/or the symposium per se. To obtain a balanced viewpoint, one speaker (Dr. J. Appel) was selected because of his contributions to the field of DD research and because he could address the issues as an informed insider. The other speaker (Dr. L. Harris) has had extensive experience in the field of drug abuse research and is familiar with the technique of DD but does not actively conduct such studies in his own laboratory; his comments may be taken as those of an unbiased outsider. Dr. Harris was given the difficult task of critiquing the entire symposium. The Scientific Organizing Committee for the symposium was composed of Dr. Richard A. Glennon (United States, chair), Dr. Toby Järbe (Sweden, cochair), Dr. John A. Rosecrans (United States), Dr. Ian P. Stolerman (United Kingdom), and Dr. Alice M. Young (United States). The Scientific Organizing Committee was assisted by a local organizing committee without whose help the symposium would have been impossible. The
Recommended publications
  • Chemicals in the Fourth Report and Updated Tables Pdf Icon[PDF

    Chemicals in the Fourth Report and Updated Tables Pdf Icon[PDF

    Chemicals in the Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, March 2021 CDC’s Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, March 2021 provides exposure data on the following chemicals or classes of chemicals. The Updated Tables contain cumulative data from national samples collected beginning in 1999–2000 and as recently as 2015-2016. Not all chemicals were measured in each national sample. The data tables are available at https://www.cdc.gov/exposurereport. An asterisk (*) indicates the chemical has been added since publication of the Fourth National Report on Human Exposure to Environmental Chemicals in 2009. Adducts of Hemoglobin Acrylamide Formaldehyde* Glycidamide Tobacco Alkaloids and Metabolites Anabasine* Anatabine* Cotinine Cotinine-n-oxide* Hydroxycotinine* Trans-3’-hydroxycotinine* 1-(3-Pyridyl)-1-butanol-4-carboxylic acid* Nicotine* Nicotine-N’-oxide* Nornicotine* Tobacco-Specific Nitrosamines (TSNAs) N’-Nitrosoanabasine (NAB)* N’-Nitrosoanatabine (NAT)* N’-Nitrosonornicotine (NNN)* Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL)* Volatile N-nitrosamines (VNAs) N-Nitrosodiethylamine (NDEA)* N-Nitrosoethylmethylamine (NMEA)* N-Nitrosomorpholine (NMOR)* N-Nitrosopiperidine (NPIP)* N-Nitrosopyrrolidine (NPYR)* Disinfection By-Products Bromodichloromethane Dibromochloromethane Tribromomethane (Bromoform) Trichloromethane (Chloroform) Personal Care and Consumer Product Chemicals and Metabolites Benzophenone-3 Bisphenol A Bisphenol F* Bisphenol
  • Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence

    Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence

    Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence Christie D. Fowler, Jill R. Turner, and M. Imad Damaj Contents 1 Introduction 2 Basic Neurocircuitry of Nicotine Addiction 3 Role of Nicotinic Receptors in Nicotine Dependence and Brain Function 4 Modulatory Factors That Influence nAChR Expression and Signaling 5 Genomics and Genetics of Nicotine Dependence 5.1 Overview 5.2 Human and Animal Genetic Studies 5.3 Transcriptionally Adaptive Changes 6 Other Constituents in Nicotine and Tobacco Products Mediating Dependence 7 Therapeutic Approaches for Tobacco and Nicotine Dependence 7.1 Nicotine Replacement Therapies 7.2 Varenicline and Bupropion 7.3 Novel Approaches 8 Conclusion References Abstract Tobacco dependence is a leading cause of preventable disease and death world- wide. Nicotine, the main psychoactive component in tobacco cigarettes, has also C. D. Fowler Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA J. R. Turner Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA M. Imad Damaj (*) Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA Translational Research Initiative for Pain and Neuropathy at VCU, Richmond, VA, USA e-mail: [email protected] # Springer Nature Switzerland AG 2019 Handbook of Experimental Pharmacology, https://doi.org/10.1007/164_2019_252 C. D. Fowler et al. been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms under- lying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field’s current understanding of nicotine’s actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence.
  • Sílvia Vilares Conde

    Sílvia Vilares Conde

    Sílvia Vilares Conde FUNCTIONAL SIGNIFICANCE OF ADENOSINE IN CAROTID BODY CHEMOSENSORY ACTIVITY IN CONTROL AND CHRONICALLY HYPOXIC ANIMALS Lisboa, 2007 a Dissertation presented to obtain the PhD degree in “Ciências da Vida – Especialidade Farmacologia” at the Faculdade de Ciências Médicas, Universidade Nova de Lisboa and Biotecnología: Aplicaciones Biomédicas at the Facultad de Medicina, Universidad de Valladolid Supervised by Profs. Constancio Gonzalez, Emília Monteiro and Ana Obeso. b Realizado com o apoio da Fundação para a Ciência e Tecnologia, SFRH/BD/14178/2003 financiada pelo POCI 2010 no âmbito da Formação avançada para a Ciência, Medida IV.3. c To my mum and dad d This work: Originated the following publications: - Conde S.V., Obeso A., Vicario I., Rigual R., Rocher A. and Gonzalez C. (2006), Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors, J. Neurochem., 98, 616-628. (Chapter 3) - Conde S.V. and Monteiro E.C. (2006), Activation of nicotinic ACh receptors with α4 subunits induces adenosine release at the rat carotid body, Br. J. Pharmacol., 147, 783-789. (Chapter 2) - Conde S.V. and Monteiro E.C. (2004), Hypoxia induces adenosine release from the rat carotid body, J. Neurochem., 89 (5), 1148-1156. (Chapter 1) - Conde S.V. and Monteiro E.C. (2003), Adenosine-acetylcholine interactions at the rat carotid body, In: “Chemoreception: From cellular signalling to functional plasticity”, JM Pequinot et al. (Eds), Klumer Academic Press London, 305-311. (Chapter 2) Won the following awards: - 1st Prize “De Castro-Heymans–Neil Award” awarded by ISAC (International Society for Arterial Chemoreception) to the best work presented by a Young Researcher each triennial ISAC Meeting, 2002 - Pfizer Honor Young Researcher Prize awarded by the Portuguese Society of Medical Sciences, 2002 e Functional significance of adenosine in carotid body chemoreception PhD thesis, Silvia Vilares Conde INDEX Page List of Figures and Tables………………………………………………………..
  • A Role for Sigma Receptors in Stimulant Self Administration and Addiction

    A Role for Sigma Receptors in Stimulant Self Administration and Addiction

    Pharmaceuticals 2011, 4, 880-914; doi:10.3390/ph4060880 OPEN ACCESS pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Review A Role for Sigma Receptors in Stimulant Self Administration and Addiction Jonathan L. Katz *, Tsung-Ping Su, Takato Hiranita, Teruo Hayashi, Gianluigi Tanda, Theresa Kopajtic and Shang-Yi Tsai Psychobiology and Cellular Pathobiology Sections, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, 21224, USA * Author to whom correspondence should be addressed; E-Mail: [email protected]. Received: 16 May 2011; in revised form: 11 June 2011 / Accepted: 13 June 2011 / Published: 17 June 2011 Abstract: Sigma1 receptors (σ1Rs) represent a structurally unique class of intracellular proteins that function as chaperones. σ1Rs translocate from the mitochondria-associated membrane to the cell nucleus or cell membrane, and through protein-protein interactions influence several targets, including ion channels, G-protein-coupled receptors, lipids, and other signaling proteins. Several studies have demonstrated that σR antagonists block stimulant-induced behavioral effects, including ambulatory activity, sensitization, and acute toxicities. Curiously, the effects of stimulants have been blocked by σR antagonists tested under place-conditioning but not self-administration procedures, indicating fundamental differences in the mechanisms underlying these two effects. The self administration of σR agonists has been found in subjects previously trained to self administer cocaine. The reinforcing effects of the σR agonists were blocked by σR antagonists. Additionally, σR agonists were found to increase dopamine concentrations in the nucleus accumbens shell, a brain region considered important for the reinforcing effects of abused drugs.
  • Withdrawing Benzodiazepines in Primary Care

    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.
  • Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report

    Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report

    Project No. TREN-05-FP6TR-S07.61320-518404-DRUID DRUID Driving under the Influence of Drugs, Alcohol and Medicines Integrated Project 1.6. Sustainable Development, Global Change and Ecosystem 1.6.2: Sustainable Surface Transport 6th Framework Programme Deliverable 4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Due date of deliverable: 21.07.2011 Actual submission date: 21.07.2011 Revision date: 21.07.2011 Start date of project: 15.10.2006 Duration: 48 months Organisation name of lead contractor for this deliverable: UVA Revision 0.0 Project co-funded by the European Commission within the Sixth Framework Programme (2002-2006) Dissemination Level PU Public PP Restricted to other programme participants (including the Commission x Services) RE Restricted to a group specified by the consortium (including the Commission Services) CO Confidential, only for members of the consortium (including the Commission Services) DRUID 6th Framework Programme Deliverable D.4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Page 1 of 243 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Authors Trinidad Gómez-Talegón, Inmaculada Fierro, M. Carmen Del Río, F. Javier Álvarez (UVa, University of Valladolid, Spain) Partners - Silvia Ravera, Susana Monteiro, Han de Gier (RUGPha, University of Groningen, the Netherlands) - Gertrude Van der Linden, Sara-Ann Legrand, Kristof Pil, Alain Verstraete (UGent, Ghent University, Belgium) - Michel Mallaret, Charles Mercier-Guyon, Isabelle Mercier-Guyon (UGren, University of Grenoble, Centre Regional de Pharmacovigilance, France) - Katerina Touliou (CERT-HIT, Centre for Research and Technology Hellas, Greece) - Michael Hei βing (BASt, Bundesanstalt für Straßenwesen, Germany).
  • Nitric Oxide and the Neurotoxic Effects of Methamphetamine and 3,4-Methylenedioxymethamphetamine1

    Nitric Oxide and the Neurotoxic Effects of Methamphetamine and 3,4-Methylenedioxymethamphetamine1

    0022-3565/97/2802-0941$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 280, No. 2 Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. JPET 280:941–947, 1997 Nitric Oxide and the Neurotoxic Effects of Methamphetamine and 3,4-Methylenedioxymethamphetamine1 TERRI TARASKA and KEVIN T. FINNEGAN Departments of Psychiatry (T.T., K.T.F.), Pharmacology and Toxicology (K.T.F.) and Neuroscience (K.T.F.), University of Utah School of Medicine and the Veterans Administration Medical Center, Salt Lake City, Utah Accepted for publication October 21, 1996 ABSTRACT The role of nitric oxide (NO) in the long-term, amine-depleting antagonized the hyperthermic effects of METH, reducing co- effects of methamphetamine (METH) and 3,4-methyl- lonic temperatures in mice by a mean of 3°C, in comparison enedioxymethamphetamine (MDMA) was investigated in the with control. Moreover, if the hypothermic effects of L-NAME in rodent central nervous system. The NO synthase inhibitor NG- METH-treated mice were prevented by raising the ambient nitro-L-arginine methyl ester (L-NAME) antagonized the dopa- room temperature, the dopamine-depleting actions of the stim- mine- and serotonin-depleting effects of both METH and ulant were fully restored. The latter findings suggest that it is the MDMA. The protective actions of L-NAME in METH-treated hypothermic actions of L-NAME, rather than its NO inhibitory mice were reversed by prior administration of the NO generator properties, that are responsible for the prevention of neurotox- G G isosorbide dinitrate. However, pretreatment with N -mono- icity.
  • Cerebellar Toxicity of Phencyclidine

    Cerebellar Toxicity of Phencyclidine

    The Journal of Neuroscience, March 1995, 75(3): 2097-2108 Cerebellar Toxicity of Phencyclidine Riitta N&kki, Jari Koistinaho, Frank Ft. Sharp, and Stephen M. Sagar Department of Neurology, University of California, and Veterans Affairs Medical Center, San Francisco, California 94121 Phencyclidine (PCP), clizocilpine maleate (MK801), and oth- Phencyclidine (PCP), dizocilpine maleate (MK801), and other er NMDA antagonists are toxic to neurons in the posterior NMDA receptor antagonistshave attracted increasing attention cingulate and retrosplenial cortex. To determine if addition- becauseof their therapeutic potential. These drugs have neuro- al neurons are damaged, the distribution of microglial ac- protective properties in animal studies of focal brain ischemia, tivation and 70 kDa heat shock protein (HSP70) induction where excitotoxicity is proposedto be an important mechanism was studied following the administration of PCP and of neuronal cell death (Dalkara et al., 1990; Martinez-Arizala et MK801 to rats. PCP (10-50 mg/kg) induced microglial ac- al., 1990). Moreover, NMDA antagonists decrease neuronal tivation and neuronal HSP70 mRNA and protein expression damage and dysfunction in other pathological conditions, in- in the posterior cingulate and retrosplenial cortex. In ad- cluding hypoglycemia (Nellgard and Wieloch, 1992) and pro- dition, coronal sections of the cerebellar vermis of PCP (50 longed seizures(Church and Lodge, 1990; Faingold et al., 1993). mg/kg) treated rats contained vertical stripes of activated However, NMDA antagonists are toxic to certain neuronal microglial in the molecular layer. In the sagittal plane, the populations in the brain. Olney et al. (1989) demonstratedthat microglial activation occurred in irregularly shaped patch- the noncompetitive NMDA antagonists,PCP, MK801, and ke- es, suggesting damage to Purkinje cells.
  • (19) United States (12) Patent Application Publication (10) Pub

    (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

    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.
  • A Bill to Repeal Criminal Drug Laws: Replacing Prohibition with Regulation Joseph L

    A Bill to Repeal Criminal Drug Laws: Replacing Prohibition with Regulation Joseph L

    Hofstra Law Review Volume 18 | Issue 3 Article 10 1990 A Bill to Repeal Criminal Drug Laws: Replacing Prohibition with Regulation Joseph L. Galiber Follow this and additional works at: http://scholarlycommons.law.hofstra.edu/hlr Part of the Law Commons Recommended Citation Galiber, Joseph L. (1990) "A Bill to Repeal Criminal Drug Laws: Replacing Prohibition with Regulation," Hofstra Law Review: Vol. 18: Iss. 3, Article 10. Available at: http://scholarlycommons.law.hofstra.edu/hlr/vol18/iss3/10 This document is brought to you for free and open access by Scholarly Commons at Hofstra Law. It has been accepted for inclusion in Hofstra Law Review by an authorized administrator of Scholarly Commons at Hofstra Law. For more information, please contact [email protected]. Galiber: A Bill to Repeal Criminal Drug Laws: Replacing Prohibition with R A BILL TO REPEAL CRIMINAL DRUG LAWS: REPLACING PROHIBITION WITH REGULATION Joseph L. Galiber* Conventional wisdom obliges elected officials to beat the narcodrums loudly and incessantly, and to demand increasingly harsh criminal penalties for the sale and use of illegal drugs.' It is reasonable to wonder why I, a senator, would dare submit a bill2 to the New York State Legislature which would regulate all drugs cur- rently proscribed as illegal in precisely the same manner as alcohol.3 The short answer is that the use of the criminal law to control drug use has not, and never will, have anything more than a costly and marginal impact on drug consumption.4 Despite all the public hyperventilation, drug consumption remains a private, consensual * New York State Senator; B.A.
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE

    )&F1y3x PHARMACEUTICAL APPENDIX to THE

    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE