Neurotechnologies As Weapons in National Intelligence and Defense – an Overview James Giordano, Phd*1-3 and Rachel Wurzman, Phd(C)4
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(12) Patent Application Publication (10) Pub. No.: US 2017/0020892 A1 Thompson Et Al
US 20170020892A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0020892 A1 Thompson et al. (43) Pub. Date: Jan. 26, 2017 (54) USE OF NEGATIVE MODULATORS OF Related U.S. Application Data GABA RECEPTORS CONTAINING ALPHAS SUBUNITS AS FAST ACTING (60) Provisional application No. 61/972,446, filed on Mar. ANTDEPRESSANTS 31, 2014. (71) Applicant: University of Maryland, Baltimore, Publication Classification Baltimore, MD (US) (51) Int. Cl. A 6LX 3/557 (2006.01) (72) Inventors: Scott Thompson, Baltimore, MD (US); A6II 3/53 (2006.01) Mark D. Kvarta, Ellicott City, MD A6II 45/06 (2006.01) (US); Adam Van Dyke, Baltimore, MD (52) U.S. Cl. (US) CPC ........... A61 K3I/55.17 (2013.01); A61K 45/06 (2013.01); A61 K3I/53 (2013.01) (73) Assignee: University of Maryland, Baltimore, Baltimore, MD (US) (57) ABSTRACT Embodiments of the disclosure include methods and com (21) Appl. No.: 15/300,984 positions related to treatment of one or more medical conditions with one or more negative modulators of GABA (22) PCT Filed: Mar. 31, 2015 receptors. In specific embodiments, depression and/or Sui cidability is treated or ameliorated or prevented with one or (86) PCT No.: PCT/US2O15/023667 more negative modulators of GABA receptors, such as a S 371 (c)(1), partial inverse agonist of a GABA receptor comprising an (2) Date: Sep. 30, 2016 alpha5 subunit. Patent Application Publication Jan. 26, 2017. Sheet 1 of 12 US 2017/002O892 A1 ×1/ /|\ Patent Application Publication Jan. 26, 2017. Sheet 3 of 12 US 2017/002O892 A1 & Patent Application Publication Jan. -
Index Vol. 12-15
353 INDEX VOL. 12-15 Die Stichworte des Sachregisters sind in der jeweiligen Sprache der einzelnen Beitrage aufgefiihrt. Les termes repris dans la Table des matieres sont donnes selon la langue dans laquelle l'ouvrage est ecrit. The references of the Subject Index are given in the language of the respective contribution. 14 AAG (Alpha-acid glycoprotein) 120 14 Adenosine 108 12 Abortion 151 12 Adenosine-phosphate 311 13 Abscisin 12, 46, 66 13 Adenosine-5'-phosphosulfate 148 14 Absorbierbarkeit 317 13 Adenosine triphosphate 358 14 Absorption 309, 350 15 S-Adenosylmethionine 261 13 Absorption of drugs 139 13 Adipaenin (Spasmolytin) 318 14 - 15 12 Adrenal atrophy 96 14 Absorptionsgeschwindigkeit 300, 306 14 - 163, 164 14 Absorptionsquote 324 13 Adrenal gland 362 14 ACAI (Anticorticocatabolic activity in 12 Adrenalin(e) 319 dex) 145 14 - 209, 210 12 Acalo 197 15 - 161 13 Aceclidine (3-Acetoxyquinuclidine) 307, 13 {i-Adrenergic blockers 119 308, 310, 311, 330, 332 13 Adrenergic-blocking activity 56 13 Acedapsone 193,195,197 14 O(-Adrenergic blocking drugs 36, 37, 43 13 Aceperone (Acetabutone) 121 14 {i-Adrenergic blocking drugs 38 12 Acepromazin (Plegizil) 200 14 Adrenergic drugs 90 15 Acetanilid 156 12 Adrenocorticosteroids 14, 30 15 Acetazolamide 219 12 Adrenocorticotropic hormone (ACTH) 13 Acetoacetyl-coenzyme A 258 16,30,155 12 Acetohexamide 16 14 - 149,153,163,165,167,171 15 1-Acetoxy-8-aminooctahydroindolizin 15 Adrenocorticotropin (ACTH) 216 (Slaframin) 168 14 Adrenosterone 153 13 4-Acetoxy-1-azabicyclo(3, 2, 2)-nonane 12 Adreson 252 -
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. -
(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. -
The Effect of Diazepam on Neonatal Seizure: in Vivo 31Pand 'H NMR Study1
003 1-3998/89/2501-0027$02.00/0 PEDIATRIC RESEARCH Vol. 25, No. 1, 1989 Copyright O 1989 International Pediatric Research Foundation, Inc. Printed in U.S.A. The Effect of Diazepam on Neonatal Seizure: In Vivo 31Pand 'H NMR Study1 RICHARD S. K. YOUNG, BENJAMIN CHEN, OGNEN A. C. PETROFF, JOHN C. GORE, BARRETT E. COWAN, EDWARD J. NOVOTNY, JR., MABEL WONG, AND KAYE ZUCKERMAN Departments of Pediatrics [R.S.K. Y., M. W., K.Z.], Neurology [R.S.K. Y., O.A.C.P., E.J.N.], and Diagnostic Radiology [B.C., J.C.G.], Yale University School of Medicine, New Haven, Connecticut 06510-8064, and Department of Medicine [B.E.C.] Stanford University Medical School, Stanford, California 94305 ABSTRACI'. It is assumed that when anticonvulsants this study, four types of investigations were performed: in vivo arrest seizure, there is rapid return of brain high energy 31PNMR to follow brain high energy phosphate metabolism and phosphates and brain lactate to control values. To test this brain pH; in vivo 'H NMR to measure brain lactate; in vitro 'H hypothesis, diazepam was administered to neonatal dogs NMR spectroscopy to determine concentrations of brain excita- during flurothyl-induced seizure. In vivo 3'P nuclear mag- tory and inhibitory amino acids; and iodoantipyrine autoradi- netic resonance spectroscopy disclosed that diazepam ography to assess regional cerebral blood flow. quickly arrested electrographic seizure and restored brain phosphocreatine and inorganic phosphate to baseline val- ues. In contrast, in vivo 'H nuclear magnetic resonance MATERIALS AND METHODS spectroscopic measurements showed that arrest of seizure Animal preparation. -
Ion Channels
UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. -
Norepinephrine-Deficient Mice Have Increased Susceptibility to Seizure
The Journal of Neuroscience, December 15, 1999, 19(24):10985–10992 Norepinephrine-Deficient Mice Have Increased Susceptibility to Seizure-Inducing Stimuli Patricia Szot,1,6 David Weinshenker,2,5 Sylvia S. White,1 Carol A. Robbins,3 Nicole C. Rust,2,5 Philip A. Schwartzkroin,3,4 and Richard D. Palmiter2,5 Departments of 1Psychiatry and Behavioral Science, 2Biochemistry, 3Neurological Surgery, and 4Physiology/Biophysics and 5Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, and 6GRECC, Puget Sound Health Care System, Seattle, Washington 98108 Several lines of evidence suggest that norepinephrine (NE) can acid. c-Fos mRNA expression in the cortex, hippocampus (CA1 modulate seizure activity. However, the experimental methods and CA3), and amygdala was increased in Dbh 2/2 mice in used in the past cannot exclude the possible role of other association with flurothyl-induced seizures. Enhanced seizure neurotransmitters coreleased with NE from noradrenergic ter- susceptibility to flurothyl and increased seizure-induced c-fos minals. We have assessed the seizure susceptibility of geneti- mRNA expression were reversed by pretreatment with L-threo- cally engineered mice that lack NE. Seizure susceptibility was 3,4-dihydroxyphenylserine, which partially restores the NE con- determined in the dopamine b-hydroxylase null mutant (Dbh tent in Dbh 2/2 mice. These genetically engineered mice 2/2) mouse using four different convulsant stimuli: 2,2,2- confirm unambiguously the potent effects of the noradrenergic trifluroethyl ether (flurothyl), pentylenetetrazol (PTZ), kainic acid, system in modulating epileptogenicity and illustrate the unique and high-decibel sound. Dbh 2/2 mice demonstrated en- opportunity offered by Dbh 2/2 mice for elucidating the path- hanced susceptibility (i.e., lower threshold) compared with lit- ways through which NE can regulate seizure activity. -
Control of Epileptic Seizures by the Basal Ganglia: Clinical and Experimental Approaches Feddersen Berend
Control of epileptic seizures by the basal ganglia: clinical and experimental approaches Feddersen Berend To cite this version: Feddersen Berend. Control of epileptic seizures by the basal ganglia: clinical and experimental ap- proaches. Neurons and Cognition [q-bio.NC]. Université Joseph-Fourier - Grenoble I, 2009. English. tel-00413972 HAL Id: tel-00413972 https://tel.archives-ouvertes.fr/tel-00413972 Submitted on 7 Sep 2009 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Ecole Doctorale Chimie et Sciences du Vivant UNIVERSITE JOSEPH FOURIER GRENOBLE Thèse Neuroscience - Neurobiologie Berend Feddersen Control of epileptic seizures by the basal ganglia: clinical and experimental approaches Soutenue publiquement le: 10.07.2009 Membres du jury : Franck Semah (Rapporteur 1) Stephane Charpier (Rapporteur 2) Philippe Kahane Soheyl Noachtar Antoine Depaulis (Directeur de thèse) Colin Deransart 1 ACKNOWLEDGEMENTS Many fantastic people were inolved in this thesis, whom I want to thank deeply for all their help and support. I want to thank my supervisors Soheyl Noachtar, Antoine Depaulis and Colin Deransart for all their help and fruitfull discussions in every kind of situation. Sohyel Nochtar teached me in a perfect structured manner clinical epileptology and gave me always all the support I needed, especially for my stay in Grenoble. -
Neurochemical and Behavioral Features in Genetic Absence Epilepsy and in Acutely Induced Absence Seizures
Hindawi Publishing Corporation ISRN Neurology Volume 2013, Article ID 875834, 48 pages http://dx.doi.org/10.1155/2013/875834 Review Article Neurochemical and Behavioral Features in Genetic Absence Epilepsy and in Acutely Induced Absence Seizures A. S. Bazyan1 and G. van Luijtelaar2 1 Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, Russian Federation, 5A Butlerov Street, Moscow 117485, Russia 2 Biological Psychology, Donders Centre for Cognition, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands Correspondence should be addressed to G. van Luijtelaar; [email protected] Received 21 January 2013; Accepted 6 February 2013 Academic Editors: R. L. Macdonald, Y. Wang, and E. M. Wassermann Copyright © 2013 A. S. Bazyan and G. van Luijtelaar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The absence epilepsy typical electroencephalographic pattern of sharp spikes and slow waves (SWDs) is considered to be dueto an interaction of an initiation site in the cortex and a resonant circuit in the thalamus. The hyperpolarization-activated cyclic nucleotide-gated cationic Ih pacemaker channels (HCN) play an important role in the enhanced cortical excitability. The role of thalamic HCN in SWD occurrence is less clear. Absence epilepsy in the WAG/Rij strain is accompanied by deficiency of the activity of dopaminergic system, which weakens the formation of an emotional positive state, causes depression-like symptoms, and counteracts learning and memory processes. -
Ethanol Acts Directly on Extrasynaptic Subtypes of GABAA Receptors to Increase Tonic Inhibition Vijayalakshmi Santhakumara, Martin Wallnerb, Thomas S
Alcohol 41 (2007) 211e221 Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition Vijayalakshmi Santhakumara, Martin Wallnerb, Thomas S. Otisc,* aDepartment of Neurology, David Geffen School of Medicine, University of California, Box 951763, 63-314 CHS, Los Angeles, CA 90095-1763, USA bDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Box 951763, 63-314 CHS, Los Angeles, CA 90095-1763, USA cDepartment of Neurobiology, David Geffen School of Medicine, University of California, Box 951763, 63-314 CHS, Los Angeles, CA 90095-1763, USA Received 5 February 2007; received in revised form 20 April 2007; accepted 20 April 2007 Abstract Based on the similarity of ethanol intoxication to the behavioral effects of drugs known to target g-aminobutyric acid type A (GABAA) receptors (GABARs), it has been suspected for decades that ethanol facilitates the activity of GABA. Even so, it has been surprisingly dif- ficult to identify molecular targets of ethanol. Research conducted over the past several years suggests that a subclass of GABARs (those containing d subunits) responds in a relevant concentration range to ethanol. Although d subunit-containing GABARs are not ubiquitously expressed at inhibitory synapses like their g subunit-containing, synaptic counterparts, they are found in many neurons in extrasynaptic locations. Here, they give rise to a tonic form of inhibition that can potently suppress neuronal excitability. Studies have shown that both recombinant and native d subunit-containing GABARs (1) are modulated by behaviorally relevant (i.e., low millimolar) concentrations of ethanol, (2) directly bind ethanol over the same concentration range, (3) show altered function upon single amino substitutions linked to changes in behavioral responsiveness to ethanol, and (4) are a site of action of Ro15-4513, a competitive antagonist of ethanol binding and a drug which prevents many of the behavioral aspects of ethanol intoxication. -
Product Update Price List Winter 2014 / Spring 2015 (£)
Product update Price list winter 2014 / Spring 2015 (£) Say to affordable and trusted life science tools! • Agonists & antagonists • Fluorescent tools • Dyes & stains • Activators & inhibitors • Peptides & proteins • Antibodies hellobio•com Contents G protein coupled receptors 3 Glutamate 3 Group I (mGlu1, mGlu5) receptors 3 Group II (mGlu2, mGlu3) receptors 3 Group I & II receptors 3 Group III (mGlu4, mGlu6, mGlu7, mGlu8) receptors 4 mGlu – non-selective 4 GABAB 4 Adrenoceptors 4 Other receptors 5 Ligand Gated ion channels 5 Ionotropic glutamate receptors 5 NMDA 5 AMPA 6 Kainate 7 Glutamate – non-selective 7 GABAA 7 Voltage-gated ion channels 8 Calcium Channels 8 Potassium Channels 9 Sodium Channels 10 TRP 11 Other Ion channels 12 Transporters 12 GABA 12 Glutamate 12 Other 12 Enzymes 13 Kinase 13 Phosphatase 14 Hydrolase 14 Synthase 14 Other 14 Signaling pathways & processes 15 Proteins 15 Dyes & stains 15 G protein coupled receptors Cat no. Product name Overview Purity Pack sizes and prices Glutamate: Group I (mGlu1, mGlu5) receptors Agonists & activators HB0048 (S)-3-Hydroxyphenylglycine mGlu1 agonist >99% 10mg £112 50mg £447 HB0193 CHPG Sodium salt Water soluble, selective mGlu5 agonist >99% 10mg £59 50mg £237 HB0026 (R,S)-3,5-DHPG Selective mGlu1 / mGlu5 agonist >99% 10mg £70 50mg £282 HB0045 (S)-3,5-DHPG Selective group I mGlu receptor agonist >98% 1mg £42 5mg £83 10mg £124 HB0589 S-Sulfo-L-cysteine sodium salt mGlu1α / mGlu5a agonist 10mg £95 50mg £381 Antagonists HB0049 (S)-4-Carboxyphenylglycine Competitive, selective group 1 -
At the Gabaa Receptor
THE EFFECTS OF CHRONIC ETHANOL INTAKE ON THE ALLOSTERIC INTERACTION BE T WEEN GABA AND BENZODIAZEPINE AT THE GABAA RECEPTOR THESIS Presented to the Graduate Council of the University of North Texas in Partial Fulfillment of the Requirements For the Degree of MASTER OF SCIENCE By Jianping Chen, B.S., M.S. Denton, Texas May, 1992 Chen, Jianping, The Effects of Chronic Ethanol Intake on the Allsteric Interaction Between GABA and BenzodiazeDine at the GABAA Receptor. Master of Science (Biomedical Sciences/Pharmacology), May, 1992, 133 pp., 4 tables, 3.0 figures, references, 103 titles. This study examined the effects of chronic ethanol intake on the density, affinity, and allosteric modulation of rat brain GABAA receptor subtypes. In the presence of GABA, the apparent affinity for the benzodiazepine agonist flunitrazepam was increased and for the inverse agonist R015-4513 was decreased. No alteration in the capacity of GABA to modulate flunitrazepam and R015-4513 binding was observed in membranes prepared from cortex, hippocampus or cerebellum following chronic ethanol intake or withdrawal. The results also demonstrate two different binding sites for [3H]RO 15-4513 in rat cerebellum that differ in their affinities for diazepam. Chronic ethanol treatment and withdrawal did not significantly change the apparent affinity or density of these two receptor subtypes. ACKNOWLEDGEMENT I would like to express my sincere thanks to my major professor, Dr. Michael W. Martin. .I deeply appreciate his guidance and direction which initiated this study, and his kindness in sharing his laboratory facilities with me. His suggestions, patience, encouragement and support in the laboratory have contributed significantly to my understanding of the receptor mechanism of drug action.