Medications in Patients with Dementia and Behavioral Disturbance
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Interplay Between Gating and Block of Ligand-Gated Ion Channels
brain sciences Review Interplay between Gating and Block of Ligand-Gated Ion Channels Matthew B. Phillips 1,2, Aparna Nigam 1 and Jon W. Johnson 1,2,* 1 Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA; [email protected] (M.B.P.); [email protected] (A.N.) 2 Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA * Correspondence: [email protected]; Tel.: +1-(412)-624-4295 Received: 27 October 2020; Accepted: 26 November 2020; Published: 1 December 2020 Abstract: Drugs that inhibit ion channel function by binding in the channel and preventing current flow, known as channel blockers, can be used as powerful tools for analysis of channel properties. Channel blockers are used to probe both the sophisticated structure and basic biophysical properties of ion channels. Gating, the mechanism that controls the opening and closing of ion channels, can be profoundly influenced by channel blocking drugs. Channel block and gating are reciprocally connected; gating controls access of channel blockers to their binding sites, and channel-blocking drugs can have profound and diverse effects on the rates of gating transitions and on the stability of channel open and closed states. This review synthesizes knowledge of the inherent intertwining of block and gating of excitatory ligand-gated ion channels, with a focus on the utility of channel blockers as analytic probes of ionotropic glutamate receptor channel function. Keywords: ligand-gated ion channel; channel block; channel gating; nicotinic acetylcholine receptor; ionotropic glutamate receptor; AMPA receptor; kainate receptor; NMDA receptor 1. Introduction Neuronal information processing depends on the distribution and properties of the ion channels found in neuronal membranes. -
(12) United States Patent (10) Patent No.: US 8,603,526 B2 Tygesen Et Al
USOO8603526B2 (12) United States Patent (10) Patent No.: US 8,603,526 B2 Tygesen et al. (45) Date of Patent: Dec. 10, 2013 (54) PHARMACEUTICAL COMPOSITIONS 2008. O152595 A1 6/2008 Emigh et al. RESISTANT TO ABUSE 2008. O166407 A1 7/2008 Shalaby et al. 2008/0299.199 A1 12/2008 Bar-Shalom et al. 2008/0311205 A1 12/2008 Habib et al. (75) Inventors: Peter Holm Tygesen, Smoerum (DK); 2009/0022790 A1 1/2009 Flath et al. Jan Martin Oevergaard, Frederikssund 2010/0203129 A1 8/2010 Andersen et al. (DK); Karsten Lindhardt, Haslev (DK); 2010/0204259 A1 8/2010 Tygesen et al. Louise Inoka Lyhne-versen, Gentofte 2010/0239667 A1 9/2010 Hemmingsen et al. (DK); Martin Rex Olsen, Holbaek 2010, O291205 A1 11/2010 Downie et al. (DK); Anne-Mette Haahr, Birkeroed 2011 O159100 A1 6/2011 Andersen et al. (DK); Jacob Aas Hoellund-Jensen, FOREIGN PATENT DOCUMENTS Frederikssund (DK); Pemille Kristine Hoeyrup Hemmingsen, Bagsvaerd DE 20 2006 014131 1, 2007 (DK) EP O435,726 8, 1991 EP O493513 7, 1992 EP O406315 11, 1992 (73) Assignee: Egalet Ltd., London (GB) EP 1213014 6, 2002 WO WO 89,09066 10, 1989 (*) Notice: Subject to any disclaimer, the term of this WO WO91,040 15 4f1991 patent is extended or adjusted under 35 WO WO95/22962 8, 1995 U.S.C. 154(b) by 489 days. WO WO99,51208 10, 1999 WO WOOOf 41704 T 2000 WO WO 03/024426 3, 2003 (21) Appl. No.: 12/701,429 WO WOO3,O24429 3, 2003 WO WOO3,O24430 3, 2003 (22) Filed: Feb. -
Review Memorandum
510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k062165 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Qualitative and semi-quantitative enzyme immunoassay E. Applicant: Ortho-Clinical Diagnostics, Inc. F. Proprietary and Established Names: VITROS Chemistry Products BARB Reagent VITROS Chemistry Products Calibrator 26 VITROS Chemistry Products FS Calibrator 1 VITROS Chemistry Products DAT Performance Verifiers I, II, III, IV and V G. Regulatory Information: 1. Regulation section: 21 CFR 862.3150, Barbiturates test system 21 CFR 862.3200, Clinical Toxicology Calibrator 21 CFR 862.3180, Clinical Toxicology Control 2. Classification: Class II, (reagent, calibrator) Class I, reserved (control) 3. Product code: DIS, DLJ and DIF 4. Panel: Toxicology (91) 1 H. Intended Use: 1. Intended use(s): See Indications for use. 2. Indication(s) for use: VITROS Chemistry Products BARB Reagent: For in vitro diagnostic use only. VITROS Chemistry Products BARB Reagent is used on VITROS 5,1 FS Chemistry Systems for the semi- quantitative or qualitative determination of barbiturates (BARB) in human urine using a cutoff of 200 ng/mL or 300 ng/mL. Measurements obtained with the VITROS BARB method are used in the diagnosis and treatment of barbiturates use or overdose. The VITROS Chemistry Products BARB assay is intended for use by professional laboratory personnel. It provides only a preliminary test result. A more specific alternative chemical method must be used to confirm a result with this assay. Gas Chromatograpy/Mass Spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when evaluating a preliminary positive result. -
Simultaneous Rapid HPLC Determination of Anticonvulsant Drugs in Plasma and Correlation with EMIT®
ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 1 Copyright© 1980, Institute for Clinical Science, Inc. Simultaneous Rapid HPLC Determination of Anticonvulsant Drugs in Plasma and Correlation with EMIT® RAYMOND S. RYDZEWSKI, M.S., RICHARD H. GADSDEN, P h .D.,* and CONSTANCE A. PHELPS, A.S.M.T. Division of Clinical Chemistry, Department of Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29403 ABSTRACT A method is presented for measuring simultaneously five anti-convulsants (primidone, ethosuximide, phénobarbital, carbamazepine and diphenyl- hydantoin) in serum and plasma by high-performance liquid chroma tography (H PLC) usingalphenal (5 - allyl - 5 - phenyl - barbituric acid) as the internal standard. All five drugs are separated from each other and, in the case of primidone, from its metabolite, 2 - phenyl - 2 - ethyl - malondiamide. Total HPLC time for the separation is seven minutes. The chromatography is performed on a C-8 reverse phase column with a mobile phase consisting of acetonitrile/phosphate buffer (35/65) at 25°C. The eluted drugs are detected at 220 nm and quantitated from their peak heights relative to that of the internal standard. The lower limits of detection for each drug is 200 ng per ml for primidone, 1000 ng per ml for ethosuximide, 200 ng per ml for phéno barbital, 100 ng per ml for carbamazepine and 200 ng per ml for diphenyl- hydantoin. Analytical recoveries for the five drugs ranged from 97 to 107 percent. Correlation of results for 187 specimens by enzyme-immunoassay (EMIT) was 0.981 for primidone, 0.827 for ethosuximide, 0.975 for phéno barbital, 0.889 for carbamazepine and 0.990 for diphenylhydantoin. -
Förordning Om Ändring I Förordningen (1992:1554) Om Kontroll Av Narkotika;
Príloha 11 k rozhodnutiu švédskych úradov vlády 22. februára 2018 § 79 1. ------IND- 2018 0079 S-- SK- ------ 20180302 --- --- PROJET Zbierka zákonov Švédska SFS Published on issued on 1 March 2018. The government hereby lays down1 that Annex 1 to the Ordinance (1992:1554) on the control of narcotic drugs2 shall read as set out below. This ordinance shall enter into force on 10 April 2018. On behalf of the Government ANNIKA STRANDHÄLL Lars Hedengran (Ministry of Health and Social Affairs) 1 See Directive (EU) 2015/1535 of the European Parliament and of the Council of 9 September 2015 laying down a procedure for the provision of information in the field of technical regulations and of rules on Information Society services. 2 Ordinance reprinted as 1993:784. 1 SFS Annex 13 List of substances to be considered narcotic drugs according to the Narcotic Drugs Punishments Act Stimulants of the central nervous system ethylamphetamine (2-ethylamino-1-phenylpropane) fenethylline [1-phenyl-1-piperidyl-(2)-methyl]acetate 1-phenyl-2-butylamine N-hydroxyamphetamine propylhexedrine 4-methylthioamphetamine (4-MTA) modafinil 4-methoxy-N-methylamphetamine (PMMA, 4-MMA) 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) 4-iodo-2,5-dimethoxyphenethylamine (2C-I) 2,4,5-trimethoxyamphetamine (TMA-2) 4-methylmethcathinone (mephedrone) 4-fluoramphetamine 1-(4-methoxyphenyl)-2-(methylamino)propan-1-one (methedrone) 1-(1,3-benzodioxol-5-yl)-2-pyrrolidin-1-yl-pentan-1-one (MDPV) 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butan-1-one -
Marrakesh Agreement Establishing the World Trade Organization
No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX -
Pharmaceutical Appendix to the Harmonized Tariff Schedule
Harmonized Tariff Schedule of the United States Basic Revision 3 (2021) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States Basic Revision 3 (2021) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 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. -
Abstracts Monday August 26
ABSTRACTS MONDAY AUGUST 26 KEYNOTES, SYMPOSIA, ORAL PRESENTATION SESSIONS, POSTER DISCUSSION SESSIONS, THEMATIC POSTER SESSIONS “On Air Table of contents Monday August 26, 9:00 AM – 10:00 AM ............................................................................................... 23 Keynote Lectures .................................................................................................................................. 23 Cities as unequal opportunities for good health ........................................................................................... 23 Challenges and Prospects of Environmental Epidemiology in Africa ............................................................ 24 Monday August 26 10:30 AM – 12:00 PM .............................................................................................. 25 S01: Mapping the Air Pollution Metabolome: Applications, Limitations, and the Path Forward ............... 25 Metabolic perturbations following exposures to traffic-related air pollution in a panel of commuters with and without asthma ...................................................................................................................................... 25 Traffic-Related Air Pollution Exposure and Altered Fatty Acid Oxidation Among Adolescents and Young Adults – the Interplay with Obesity .............................................................................................................. 26 The Maternal Serum Metabolome and Ambient Air Pollution Exposure during Pregnancy ....................... -
Georgia State Forensic Drugs
Comprehensive Forensic FT-IR Collection Library Listing – 4,286 spectra This extensive library contains materials not only of forensic interest but also for general problem solving and identification of unknown substances in industry and academia. The wide range of items include drugs, clandestine lab chemicals, explosives, paints, fabrics, dyes, polymers, inorganic compounds, pigments, adhesives, and other common materials. The library consists of 4,286 spectra that were acquired from a wide range of laboratories involved in forensic investigations. The collection includes the following classes of compounds: • Drugs of abuse, scheduled materials • Pharmaceuticals, vitamins and excipients • Clandestine lab materials and intermediates • Solvents, organic chemicals and hazardous chemicals • Accelerants • Lubricants and natural oils • Explosives, pyrotechnics, primers, powders and boosters • Herbal and plant material and fibers • Automobile paint vehicles, pigments, primers and clear coats • Textiles, natural and man-made fibers, carpet materials • Paints, coatings, varnishes, oils • Dyes and stains • Polymers, monomers, copolymers, plasticizers and rubbers • Inorganics, pigments, minerals and clays • Tape, adhesives, sealants, glues, caulks and putties • Crystal test derivatives and intermediates • Household chemicals, cleaning agents, surfactants and pesticide All spectra were measured using micro or macro Diamond ATR, thin films on salt windows or KBr pellets at 4 cm-1 spectral resolution. Comprehensive Forensic FT-IR Collection Index -
FOOD and DRUGS Is Composed of Nine Volumes
Food and Drugs of 21 code PART 1300 TO END Revised as of April 1, 1996 CONTAINING A CODIFICATION OF DOCUMENTS OF GENERAL APPLICABILITY AND FUTURE EFFECT AS OF APRIL 1, 1996 regulations With Ancillaries Published by the Office of the Federal Register National Archives and Records Administration as a Special Edition of the Federal Register federal VerDate 20<JUN>96 10:04 Jul 12, 1996 Jkt 167073 PO 00000 Frm 00001 Fmt 8091 Sfmt 8091 C:\CFR\21V9.FRT pfrm13 1 U.S. GOVERNMENT PRINTING OFFICE WASHINGTON : 1996 For sale by U.S. Government Printing Office Superintendent of Documents, Mail Stop: SSOP, Washington, DC 20402±9328 VerDate 20<JUN>96 10:04 Jul 12, 1996 Jkt 167073 PO 00000 Frm 00002 Fmt 8092 Sfmt 8092 C:\CFR\21V9.FRT pfrm13 ?ii Table of Contents Page Explanation ................................................................................................ v Title 21: Chapter IIÐDrug Enforcement Administration, Department of Jus- tice .................................................................................................. 3 Chapter IIIÐOffice of National Drug Control Policy .......................... 271 Finding Aids: Table of CFR Titles and Chapters ....................................................... 325 Alphabetical List of Agencies Appearing in the CFR ......................... 341 List of CFR Sections Affected ............................................................. 351 iii VerDate 20<JUN>96 10:04 Jul 12, 1996 Jkt 167073 PO 00000 Frm 00003 Fmt 8092 Sfmt 8092 C:\CFR\21V9.FRT pfrm13 Cite this Code: CFR To cite the regulations in this volume use title, part and section num- ber. Thus, 21 CFR 1301.01 refers to title 21, part 1301, section 01. iv VerDate 20<JUN>96 10:04 Jul 12, 1996 Jkt 167073 PO 00000 Frm 00004 Fmt 8092 Sfmt 8092 C:\CFR\21V9.FRT pfrm13 Explanation The Code of Federal Regulations is a codification of the general and permanent rules published in the Federal Register by the Executive departments and agen- cies of the Federal Government. -
Basic Analytical Toxicology
The World Health Organization is a specialized agency of the United Nations with primary responsibility for international health matters and public health. Through this organization, which was created in 1948, the health professions of some 190 countries exchange their knowledge and experience with the aim of making possible the attainment by all citizens of the world by the year 2000 of a level of health that will permit them to lead a socially and economically productive life. By means of direct technical cooperation with its Member States, and by stimulating such coopera tion among them, WHO promotes the development of comprehensive health services, the prevention and control of diseases, the improvement of environmental conditions, the development of human resources for health, the coordination and development of biomedical and health services research, and the planning and implementation of health programmes. These broad fields of endeavour encompass a wide variety of activities, such as developing systems of primary health care that reach the whole population of Member countries; promoting the health of mothers and children; combating malnutrition, controlling malaria and other communicable diseases including tuberculosis and leprosy; coordinating the global strategy for the prevention and control of AIDS; having achieved the eradication of smallpox, promoting mass immunization against a number of other preventable diseases; improving mental health; providing safe water supplies; and training health personnel of all categories. Progress towards better health throughout the world also demands international cooperation in such matters as establishing international standards for biological substances, pesticides and pharma ceuticals; formulating environmental health criteria; recommending international nonproprietary names for drugs; administering the International Health Regulations; revising the International Statistical Classification of Diseases and Related Health Problems and collecting and disseminating healih statistical information. -
Early Drug Discovery and the Rise of Pharmaceutical Chemistry in a Classic Monograph (Figure 5)
Drug Testing Historical and Analysis Received: 15 April 2011 Revised: 28 April 2011 Accepted: 28 April 2011 Published online in Wiley Online Library (www.drugtestinganalysis.com) DOI 10.1002/dta.301 Early drug discovery and the rise of pharmaceutical chemistry Alan Wayne Jones∗ Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature’s pharmaceuticals were all that were available to relieve man’s pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin, the first blockbuster drug.