Poster Session Imonday, December 7, 2015
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Treatment of Stimulant Use Disorders
UW PACC Psychiatry and Addictions Case Conference UW Medicine | Psychiatry and Behavioral Sciences TREATMENT OF STIMULANT USE DISORDERS Matt Iles-Shih, MD Addiction Psychiatry Fellow University Of Washington & VA Puget Sound Health Care System UW PACC ©2017 University of Washington GENERAL DISCLOSURES The University of Washington School of Medicine also gratefully acknowledges receipt of educational grant support for this activity from the Washington State Legislature through the Safety-Net Hospital Assessment, working to expand access to psychiatric services throughout Washington State. UW PACC ©2017 University of Washington SPEAKER DISCLOSURES No conflicts of interest/disclosures UW PACC ©2017 University of Washington OBJECTIVES 1. Brief overview of stimulant-related physiology & epidemiology 2. Recognizing & treating stimulant use disorders: . Diagnosis & management of acute effects (brief) . Psychotherapies (brief) . Pharmacotherapies 3. Special populations – ADHD in stimulant-abusing pts: to Rx, and how? UW PACC ©2017 University of Washington STIMULANTS: What Substances Are We Talking About? Cocaine Amphetamines: – Prescription Meds – Methamphetamine – Multiple other modified amphetamines MDMA (3,4-methylenedioxy-methamphetamine) [Note: mixed stimulant-psychodelic properties, w/↑serotonin > dopamine and abuse >> addiction.] Others: – Cathinones: Khat & Synthetics (e.g., “Bath Salts”) – Piperazine-like substances (various) – Phenylaklylpyrrolidines (various) UW PACC ©2017 University of Washington COMMONALITIES (WHAT MAKES A STIMULANT -
Determining the Role of Gabaergic Signaling in The
DETERMINING THE ROLE OF GABAERGIC SIGNALING IN THE CRANIOFACIAL DEVELOPMENT OF LARVAL ZEBRAFISH by LINDSEY L. BEEBE (Under the Direction of James D. Lauderdale) ABSTRACT Although best known as an inhibitory neurotransmitter, intriguing evidence has implicated GABA as a key signaling molecule in craniofacial development in mammals. Glutamate is converted to GABA by an enzyme called glutamic acid decarboxylase (GAD), which exists in two isoforms, GAD67 and GAD65. The GAD1 and GAD2 genes encode these isoforms, respectively. A decrease in GAD activity in the human brain is often associated with epilepsy, schizophrenia and related neurological disorders. In mice and humans, mutations in gad1, but not gad2, result in defects in palate development, and mutations in the Gabrb3 gene, which encodes the β3 subunit of the GABAA receptor, exhibit a comparable phenotype to gad1 mutations. These results suggest that GABA signaling, through the GABAA receptor, can play an important and conserved role in craniofacial development. However, the mechanism of this process is not known and cannot be easily investigated in a mammalian system. In this work, translation-blocking morpholinos against the GAD genes were used to alter expression within the larval zebrafish. While gad2 morphants looked phenotypically normal, gad1 morphant animals exhibited altered cranial structures at 1 and 7 dpf. Yet, both gad1 and gad2 morphants exhibited spontaneous seizure-like neural activity. Through the use of photoactivatable caged-morpholinos, the craniofacial deformities could be bypassed when photolysis was carried out at 24 hpf. Electrophysiological recordings showed that while dark-raised CyHQ-gad1 morphant animals looked phenotypically comparable to wild-type animals, they exhibited abnormal, seizure-like neural activity. -
Neurotransmitters-Drugs Andbrain Function.Pdf
Neurotransmitters, Drugs and Brain Function. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 Neurotransmitters, Drugs and Brain Function Neurotransmitters, Drugs and Brain Function. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 Neurotransmitters, Drugs and Brain Function Edited by R. A. Webster Department of Pharmacology, University College London, UK JOHN WILEY & SONS, LTD Chichester Á New York Á Weinheim Á Brisbane Á Singapore Á Toronto Neurotransmitters, Drugs and Brain Function. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 Copyright # 2001 by John Wiley & Sons Ltd. Bans Lane, Chichester, West Sussex PO19 1UD, UK National 01243 779777 International ++44) 1243 779777 e-mail +for orders and customer service enquiries): [email protected] Visit our Home Page on: http://www.wiley.co.uk or http://www.wiley.com All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1P0LP,UK, without the permission in writing of the publisher. Other Wiley Editorial Oces John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158-0012, USA WILEY-VCH Verlag GmbH, Pappelallee 3, D-69469 Weinheim, Germany John Wiley & Sons Australia, Ltd. -
GABA Receptors
D Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews Review No.7 / 1-2011 GABA receptors Wolfgang Froestl , CNS & Chemistry Expert, AC Immune SA, PSE Building B - EPFL, CH-1015 Lausanne, Phone: +41 21 693 91 43, FAX: +41 21 693 91 20, E-mail: [email protected] GABA Activation of the GABA A receptor leads to an influx of chloride GABA ( -aminobutyric acid; Figure 1) is the most important and ions and to a hyperpolarization of the membrane. 16 subunits with γ most abundant inhibitory neurotransmitter in the mammalian molecular weights between 50 and 65 kD have been identified brain 1,2 , where it was first discovered in 1950 3-5 . It is a small achiral so far, 6 subunits, 3 subunits, 3 subunits, and the , , α β γ δ ε θ molecule with molecular weight of 103 g/mol and high water solu - and subunits 8,9 . π bility. At 25°C one gram of water can dissolve 1.3 grams of GABA. 2 Such a hydrophilic molecule (log P = -2.13, PSA = 63.3 Å ) cannot In the meantime all GABA A receptor binding sites have been eluci - cross the blood brain barrier. It is produced in the brain by decarb- dated in great detail. The GABA site is located at the interface oxylation of L-glutamic acid by the enzyme glutamic acid decarb- between and subunits. Benzodiazepines interact with subunit α β oxylase (GAD, EC 4.1.1.15). It is a neutral amino acid with pK = combinations ( ) ( ) , which is the most abundant combi - 1 α1 2 β2 2 γ2 4.23 and pK = 10.43. -
Cell Surface Mobility of GABAB Receptors Saad Bin
Cell surface mobility of GABAB receptors Saad Bin Hannan September 2011 A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy of the University College London Department of Neuroscience, Physiology, and Pharmacology University College London Gower Street London WC1E 6BT UK Declaration ii ‘I, Saad Hannan confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis.' ____________________ Saad Hannan September 2011 To Ammu, Abbu, Polu Abstract ivi Abstract Type-B γ-aminobutyric acid receptors (GABABRs) are important for mediating slow inhibition in the central nervous system and the kinetics of their internalisation and lateral mobility will be a major determinant of their signalling efficacy. Functional GABABRs require R1 and R2 subunit co-assembly, but how heterodimerisation affects the trafficking kinetics of GABABRs is unknown. Here, an α- bungarotoxin binding site (BBS) was inserted into the N-terminus of R2 to monitor receptor mobility in live cells. GABABRs are internalised via clathrin- and dynamin- dependent pathways and recruited to endosomes. By mutating the BBS, a new technique was developed to differentially track R1a and R2 simultaneously, revealing the subunits internalise as heteromers and that R2 dominantly-affects constitutive internalisation of GABABRs. Notably, the internalisation profile of R1aR2 heteromers, but not R1a homomers devoid of their ER retention motif (R1ASA), is similar to R2 homomers in heterologous systems. The internalisation of R1aASA was slowed to that of R2 by mutating a di-leucine motif in the R1 C-terminus, indicating a new role for heterodimerisation, whereby R2 subunits slow the internalization of surface GABABRs. -
Cocaine Use Disorder
COCAINE USE DISORDER ABSTRACT Cocaine addiction is a serious public health problem. Millions of Americans regularly use cocaine, and some develop a substance use disorder. Cocaine is generally not ingested, but toxicity and death from gastrointestinal absorption has been known to occur. Medications that have been used as substitution therapy for the treatment of a cocaine use disorder include amphetamine, bupropion, methylphenidate, and modafinil. While pharmacological interventions can be effective, a recent review of pharmacological therapy for cocaine use indicates that psycho-social efforts are more consistent over medication as a treatment option. Introduction Cocaine is an illicit, addictive drug that is widely used. Cocaine addiction is a serious public health problem that burdens the healthcare system and that can be destructive to individual lives. It is impossible to know with certainty the extent of use but data from public health surveys, morbidity and mortality reports, and healthcare facilities show that there are millions of Americans who regularly take cocaine. Cocaine intoxication is a common cause for emergency room visits, and it is one drug that is most often involved in fatal overdoses. Some cocaine users take the drug occasionally and sporadically but as with every illicit drug there is a percentage of people who develop a substance use disorder. Treatment of a cocaine use disorder involves psycho-social interventions, pharmacotherapy, or a combination of the two. 1 ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com Pharmacology of Cocaine Cocaine is an alkaloid derived from the Erthroxylum coca plant, a plant that is indigenous to South America and several other parts of the world, and is cultivated elsewhere. -
DIAGNOSIS REFERENCE GUIDE A. Diagnostic Criteria for Substance
ALCOHOL & OTHER DRUG SERVICES DIAGNOSIS REFERENCE GUIDE A. Diagnostic Criteria for Substance Use Disorder See DSM-5 for criteria specific to the drugs identified as primary, secondary or tertiary. P S T (P=Primary, S=Secondary, T=Tertiary) 1. Substance is often taken in larger amounts and/or over a longer period than the patient intended. 2. Persistent attempts or one or more unsuccessful efforts made to cut down or control substance use. 3. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from effects. 4. Craving or strong desire or urge to use the substance 5. Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home. 6. Continued substance use despite having persistent or recurrent social or interpersonal problem caused or exacerbated by the effects of the substance. 7. Important social, occupational or recreational activities given up or reduced because of substance use. 8. Recurrent substance use in situations in which it is physically hazardous. 9. Substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance. 10. Tolerance, as defined by either of the following: a. Markedly increased amounts of the substance in order to achieve intoxication or desired effect; Which:__________________________________________ b. Markedly diminished effect with continued use of the same amount; Which:___________________________________________ 11. Withdrawal, as manifested by either of the following: a. The characteristic withdrawal syndrome for the substance; Which:___________________________________________ b. -
(12) Patent Application Publication (10) Pub. No.: US 2005/0215521 A1 Lalji Et Al
US 20050215521A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0215521 A1 Lalji et al. (43) Pub. Date: Sep. 29, 2005 (54) MODAFINIL COMBINATION THERAPY FOR Publication Classification IMPROVING SLEEP QUALITY (51) Int. Cl.' .................. A61K 31/724; A61K 31/7008; (76) Inventors: Karim Lalji, Sudbury, MA (US); A61K 31/4164; A61K 31/195; Timothy J. Barberich, Concord, MA A61K 31/165 (US) (52) U.S. Cl. ............................ 514/58; 514/221; 514/389; 514/561; 514/557; 514/23; Correspondence Address: 514/618; 514/469 FOLEY HOAG, LLP PATENT GROUP, WORLD TRADE CENTER WEST (57) ABSTRACT 155 SEAPORT BLVD One aspect of the present invention relates to pharmaceutical BOSTON, MA 02110 (US) compositions comprising a compound that modulates the orexin System and a Sedative agent. In a preferred embodi (21) Appl. No.: 11/018,869 ment, the compound that modulates the orexin System is (22) Filed: Dec. 21, 2004 modafinil and the Sedative agent is eSZopiclone. The phar maceutical compositions of the invention are useful in the Related U.S. Application Data treatment of various sleep disorders. In addition, the present invention relates to a method of treating a patient Suffering (60) Provisional application No. 60/531,822, filed on Dec. from a sleep abnormality or insomnia comprising adminis 22, 2003. Provisional application No. 60/541,684, tering a therapeutically effective amount of a pharmaceutical filed on Feb. 4, 2004. composition of the invention. Patent Application Publication Sep. 29, 2005 Sheet 1 of 2 US 2005/0215521 A1 Figure 1 (RS)-Zopiclone D-Malic Acid Acetone Mixing/Heating Methanol Methanol-DCooling/Crystallizatio (S)-Zopiclone D-Malate See Methanol Filtration/Washing Mother Liquors/Washes -Ge IPC (S)-Zopiclone D-Malate Patent Application Publication Sep. -
DSM-5 Diagnoses and New ICD-10-CM Codes
DSM-5 DiAgnoses And New ICD-10-CM Codes As Ordered in the DSM-5 Classification DSM-5 Recommended DSM-5 Recommended Disorder ICD-10-CM Code for use ICD-10-CM Code for use through September 30, 2017 beginning October 1, 2017 Avoidant/Restrictive Food Intake Disorder F50.89 F50.82 Alcohol Use Disorder, Mild F10.10 F10.10 Alcohol Use Disorder, Mild, In early or sustained remission F10.10 F10.11 Alcohol Use Disorder, Moderate F10.20 F10.20 Alcohol Use Disorder, Moderate, In early or sustained F10.20 F10.21 remission Alcohol Use Disorder, Severe F10.20 F10.20 Alcohol Use Disorder, Severe, In early or sustained F10.20 F10.21 remission Cannabis Use Disorder, Mild F12.10 F12.10 Cannabis Use Disorder, Mild, In early or sustained F12.10 F12.11 remission Cannabis Use Disorder, Moderate F12.20 F12.20 Cannabis Use Disorder, Moderate, In early or sustained F12.20 F12.21 remission Cannabis Use Disorder, Severe F12.20 F12.20 Cannabis Use Disorder, Severe, In early or sustained F12.20 F12.21 remission Phencyclidine Use Disorder, Mild F16.10 F16.10 Phencyclidine Use Disorder, Mild, In early or sustained F16.10 F16.11 remission Phencyclidine Use Disorder, Moderate F16.20 F16.20 Phencyclidine Use Disorder, Moderate, In early or F16.20 F16.21 sustained remission Phencyclidine Use Disorder, Severe F16.20 F16.20 Phencyclidine Use Disorder, Severe, In early or sustained F16.20 F16.21 remission Other Hallucinogen Use Disorder, Mild F16.10 F16.10 Other Hallucinogen Use Disorder, Mild, In early or F16.10 F16.11 sustained remission Other Hallucinogen Use Disorder, -
DAS Gabaerge SYSTEM
DIPLOMARBEIT Titel der Diplomarbeit „In vivo Untersuchung ausgewählter GABAA-Liganden auf das Verhalten von c57Bl/6N-Mäusen“ Verfasserin Sandra Maurer angestrebter akademischer Grad Magistra der Pharmazie (Mag.pharm.) Wien, 2013 Studienkennzahl lt. Studienblatt: A 449 Studienrichtung lt. Studienblatt: Diplomstudium Pharmazie Betreuer: Univ.-Prof. Dr. Steffen Hering DANKSAGUNG In erster Linie möchte ich mich bei Univ. Prof. Dr. Steffen Hering für die Ermöglichung dieser Diplomarbeit am Department für Pharmakologie und Toxikologie, sowie für die Bereitstellung dieses interessanten Themas bedanken. Ein Dankeschön gilt auch Mag. Dr. Sophia Khom für die hilfreichen und kompetenten Ratschläge zum Anfertigen dieser Arbeit. Herzlicher Dank gilt vor allem Mag. Juliane Hintersteiner, die mich bei allen praktischen Arbeiten begleitet, all meine Fragen geduldig beantwortet und mich mit großem Engagement unterstützt hat. Bedanken möchte ich mich weiters bei Mag. Barbara Strommer, die sich für mich eingesetzt hat, diesen Diplomarbeitsplatz zu bekommen. Auch bei meiner Familie möchte ich mich recht herzlich bedanken, dass sie mir das Studium der Pharmazie ermöglichten und mich auch in schwierigen Phasen des Studiums immer unterstützten. Besonderer Dank gilt auch meinem Freund Christoph, der immer an meiner Seite ist. INHALT A) ALLGEMEINER TEIL ................................................................................................................. 1 1. DAS GABAerge SYSTEM ..................................................................................................... -
Low Cerebral Exposure Cannot Hinder the Neuroprotective Effects of Panax Notoginsenosides
DMD Fast Forward. Published on October 23, 2017 as DOI: 10.1124/dmd.117.078436 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 78436 Low cerebral exposure cannot hinder the neuroprotective effects of panax notoginsenosides Haofeng Li, Jingcheng Xiao, Xinuo Li, Huimin Chen, Dian Kang, Yuhao Shao, Boyu Shen, Zhangpei Zhu, Xiaoxi Yin, Lin Xie, Guangji Wang, Yan Liang Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China Downloaded from dmd.aspetjournals.org at ASPET Journals on September 25, 2021 1 DMD Fast Forward. Published on October 23, 2017 as DOI: 10.1124/dmd.117.078436 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 78436 Running Title Page Panax notoginsenosides exert neuroprotective effects Corresponding author: Yan Liang Co- corresponding author: Guangji Wang Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China. Tel: +86-25-83271060 Email: [email protected] [email protected] H.L. and J.X. contributed equally to this work. Downloaded from Number of text pages: 39 Number of figures: 8 Number of references: 59 dmd.aspetjournals.org Number of words in the Abstract: 217 Number of words in the Introduction: 929 Number of words in the Discussion: 1327 at ASPET Journals on September 25, 2021 Abbreviations: -
Paired Pulse Depression in Cultured Hippocampal Neurons Is Due to a Presynaptic Mechanism Independent of GABA, Autoreceptor Activation
The Journal of Neuroscience, March 1994, 74(3): 1775-l 788 Paired Pulse Depression in Cultured Hippocampal Neurons Is Due to a Presynaptic Mechanism Independent of GABA, Autoreceptor Activation Karen S. Wilcoxi,a and Marc A. Dichter* ‘Department of Physiology and *Departments of Neurology and Pharmacology, University of Pennsylvania, School of Medicine, and Graduate Hospital, Philadelphia, PA 19104 Most rapid synaptic inhibition in the vertebrate forebrain is Under physiological conditions, synaptic inhibition in the mam- mediated by GABA acting via GABA, and GABA, postsyn- malian CNS is very labile and a downregulation of inhibitory aptic receptors. GABAergic neurotransmission exhibits fre- neurotransmissionappears to be critical for the development of quency-dependent modulation; sequential inhibitory post- someforms of synaptic plasticity, such as that occurring during synaptic currents (IPSCs) evoked with interstimulus intervals long-term potentiation. In addition, and perhaps even more between 25 msec and 4 set routinely result in the attenuation significantly, activity-dependent disinhibition is also associated of the amplitude of the second IPSC. This form of synaptic with the generation and spread of epileptic seizure activity plasticity is known as paired pulse depression (PPD). The (Dichter and Ayala, 1987). Therefore, an understanding of the mechanism of PPD is presently unknown and the experi- basic principles of inhibitory plasticity is vital to the under- ments performed in this study were designed to determine standing of both physiological and pathological synaptic plas- directly the location of the mechanism of PPD in hippocampal ticity in the CNS. neurons maintained in low-density tissue culture. Evoked Paired pulsedepression (PPD) of GABAergic inhibitory post- IPSCs were recorded between pairs of cultured neurons synaptic currents (IPSCs) is a robust example of synaptic plas- grown in relative isolation that were simultaneously being ticity in the mammalian CNS; depressionof the amplitude of recorded with the whole-cell, patch-clamp technique.