Pharmacological Aspects
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Preliminary Effects of Pagoclone, a Partial GABA Agonist, On
ORIGINAL RESEARCH Preliminary effects of pagoclone, a partial GABAA agonist, on neuropsychological performance 1 Angela F Caveney Abstract: Pagoclone is a novel cyclopyrrolone that acts as a partial GABAA receptor agonist. Bruno Giordani1 Preclinical studies suggest that pagoclone may have clinical utility as an anxiolytic agent, as George M Haig2 well as a reduced incidence of side-effects. The present study was conducted to determine whether pagoclone would affect healthy individuals’ performances on neuropsychological 1Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA; measures as a function of dose within the projected therapeutic range. Twelve healthy adult 2Neurosciences Development, Abbott subjects were randomly assigned to dosage groups in a 3-way crossover study. Participants Laboratories, Abbott Park, IL, USA were administered neuropsychological measures six hours following dosing on Day 1 and Day 6 of administration of the drug. Dose effects were noted on measures of alertness, learning, and memory and movement time. Signifi cant effects were also noted on measures of alertness, learning and memory, information processing and psychomotor speed. Overall, the results of this small, preliminary study do not support a fi nding of behavioral toxicity for these doses of pagoclone. Rather, a pattern was found of transient and mild negative effects on learning and memory scores at the highest dose administered, though these changes were small and no longer evident by the sixth day of use. Keywords: pagoclone, cyclopyrrolone, neuropsychological, memory, generalized anxiety disorder Introduction Behavioral toxicity refers to the extent to which a drug affects an individual’s ability to perform the psychomotor and cognitive tasks of everyday life (Ramaekers 1998). -
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. -
Zolpidem Tartrate) Orally Disintegrating Tablets CIV
NDA 21-412 FDA Approved Labeling Text dated April 25, 2007 Page 1 TOVALT™ ODT (zolpidem tartrate) Orally Disintegrating Tablets CIV Rx Only LB Rev. 04/07 DESCRIPTION TOVALT™ ODT (zolpidem tartrate) Orally Disintegrating Tablets is a non- benzodiazepine hypnotic of the imidazopyridine class and is available in 5 mg and 10 mg tablet strengths for oral administration. Chemically, zolpidem is N,N,6-trimethyl-2-p-tolyl-imidazo[1,2-a]pyridine-3-acetamide L-( + )-tartrate (2:1). It has the following structure: Zolpidem tartrate is a white to off-white crystalline powder that is sparingly soluble in water, alcohol, and propylene glycol. It has a molecular weight of 764.88. Each TOVALT ODT includes the following inactive ingredients: Acesulfame Potassium, Glyceryl Monostearate, Hypromellose, Stearoyl Macrogolglycerides Polyacrylate Dispersion (30%), Talc, Mannitol, Microcrystalline Cellulose, Low Substituted Hydroxypropyl Cellulose, Crospovidone, Sodium Stearyl Fumarate, Silicon Dioxide, Monoammonium Glycyrrhizinate, Natural Intense Peppermint Flavour, FD&C Blue #2 (for 10mg only). CLINICAL PHARMACOLOGY Pharmacodynamics Subunit modulation of the GABAA receptor chloride channel macromolecular complex is hypothesized to be responsible for sedative, anticonvulsant, anxiolytic, and myorelaxant NDA 21-412 FDA Approved Labeling Text dated April 25, 2007 Page 2 drug properties. The major modulatory site of the GABAA receptor complex is located on its alpha (α) subunit and is referred to as the benzodiazepine (BZ) or omega (ω) receptor. At least three subtypes of the (ω) receptor have been identified. While zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. -
Original Research Article
Original Research Article IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS ABSTRACT Objectives: At the beginning of the 20th century, Peptic Ulcer became the most prevalent disease as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) proved ineffective. Researches proved proton pump inhibitors as most successful drugs for the treatment of peptic ulcer. Hence, a ligand based pharmacophore was generated on LigandScout based on fifteen selected H+/K+ ATPase inhibitors. Methods: A pharmacophore model with three Hydrogen bond acceptors, one Hydrogen bond donor and one Hydrophobic Domain was developed. The distance between these features was estimated on Visual Molecular Dynamics (VMD) software. Results: The range between HBA-HBD was found to be 1.89-2.96A. The range between HBD-HP was 4.00-5.46A and range between HP-HBA was 1.89-2.96A. Conclusion: This research study will thus help in designing new and effective drugs for the treatment of peptic ulcer disease. Key words: Peptic Ulcer, NSAIDs, ligand, pharmacophore, Visual Molecular Dynamics INTRODUCTION Gastric H+/K+ ATPase pump is located in the parietal cells [1] and plays a crucial role in the formation of ulcers in the stomach. H pylori transmission occurs in 50% of the people worldwide [2]. A peptic ulcer is caused by Helicobacter pylori (H. pylori) infection in the gastric mucosal lining. This bacterium causes inflammation in the lining of the stomach. In response to this, gastrin hormone stimulates the gastric acid production. High levels of gastrin cause the enhance release of acid through H+/K+ ATPase pump and lead to the formation of the ulcer. -
WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 36/84 (2006.01) A61K 31/5513 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/045 (2006.01) A61P 31/22 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/522 (2006.01) A61K 45/06 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/NL20 14/050780 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 13 November 2014 (13.1 1.2014) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/903,430 13 November 2013 (13. 11.2013) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: RJG DEVELOPMENTS B.V. -
Name of Clinician Who Filled out This Form
HOME HEALTH RE-REGISTRATION/CONCURRENT REVIEW TEMPLATE ALL FIELDS WITH * ARE REQUIRED Provider EDS/CMAP ID # (Medicaid 9-digit ID) Name of clinician who filled out this form Credentials/Title Contact number _________________________________Ext: _________________ Facility/Provider Name Telephone Number Facility/Provider Service Location Member Name Medicaid/Consumer ID# DOB: AND/OR SSN: ________________ 1) *Is this a new registration for a client already in outpatient treatment within your agency/practice? YES NO If APPLICABLE, PLEASE INDICATE IF ANY OF THE FOLLOWING NEED TO BE UPDATED 2) *Behavioral Diagnoses (Primary is Required) *Diagnosis Code: _______________ *Description_________________________________________________ *Diagnostic Category: _____________________________________________________________________ Diagnosis Code: _______________ Description_________________________________________________ Diagnostic Category: _______________________________________________________________________ 3) *Primary Medical Diagnoses (Primary is required or indicate “None” or “Unknown”) *Diagnosis Code: _______________ *Description_________________________________________________ *Diagnostic Category: _____________________________________________________________________ Diagnosis Code: _______________ Description_________________________________________________ Diagnostic Category: _____________________________________________________________________ 4) *Social Elements Impacting Diagnoses (Required - Check all that apply) None Educational problems -
Handbook of Medical Psychiatry
I II III Handbook of Medical Psychiatry SECOND EDITION David P. Moore M.D. Associate Clinical Professor of Psychiatry, University of Louisville School of Medicine; Frazier Rehab Institute, Louisville, Kentucky James W. Jefferson M.D. Distinguished Senior Scientist, Madison Institute of Medicine, Inc.; Clinical Professor of Psychiatry, University of Wisconsin Medical School, Madison IV ELSEVIER MOSBY An Affiliate of Elsevier 170 S Independence Mall W. 300E. Philadelphia, PA 19106-3399 HANDBOOK OF MEDICAL PSYCHIATRY, 2nd Edition•ISBN 0-323-02911-6 Copyright © 2004, 1996,Mosby, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Health Sciences Rights Department in Philadelphia, PA, USA: phone: (+1) 215 238 7869, fax: (+1) 215 238 2239, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://www.elsevier.com.proxy.hsclib. sunysb.edu), by selecting ‘Customer Support’ and then ‘Obtaining Permissions’. NOTICE Medicine is an ever-changing field. Standard safety precautions must be followed, but as new research and clinical experience broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the method and duration of administration, and contraindications. It is the responsibility of the licensed physician, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual patient. -
Herbal Remedies and Their Possible Effect on the Gabaergic System and Sleep
nutrients Review Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep Oliviero Bruni 1,* , Luigi Ferini-Strambi 2,3, Elena Giacomoni 4 and Paolo Pellegrino 4 1 Department of Developmental and Social Psychology, Sapienza University, 00185 Rome, Italy 2 Department of Neurology, Ospedale San Raffaele Turro, 20127 Milan, Italy; [email protected] 3 Sleep Disorders Center, Vita-Salute San Raffaele University, 20132 Milan, Italy 4 Department of Medical Affairs, Sanofi Consumer HealthCare, 20158 Milan, Italy; Elena.Giacomoni@sanofi.com (E.G.); Paolo.Pellegrino@sanofi.com (P.P.) * Correspondence: [email protected]; Tel.: +39-33-5607-8964; Fax: +39-06-3377-5941 Abstract: Sleep is an essential component of physical and emotional well-being, and lack, or dis- ruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. -
Drug Points BMJ: First Published As 10.1136/Bmj.318.7192.1179 on 1 May 1999
Papers Drug points BMJ: first published as 10.1136/bmj.318.7192.1179 on 1 May 1999. Downloaded from Hepatotoxicity associated with zolpidem respectively. Retrograde endoscopic cholangiography had treatment shown no abnormality. David Karsenti, Pascal Blanc, Yannick Bacq, Etienne-Henry Metman, Six months later, in April 1997, she had had another Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire episode of abdominal pain. Eleven days later alanine Trousseau, and Service de Pharmacologie Clinique, Centre aminotransferase and ã-glutamyl transpeptidase activities Hospitalier Universitaire Bretonneau, F-37044 Tours Cedex, France had been 50 IU/l and 89 IU/l respectively. Zolpidem is a hypnotic drug of the imidazopyridine In June 1997 ultrasound examination of the biliary group. Another imidazopyridine, alpidem, has been with- tract gave normal results. On questioning she remem- 12 drawn from the market because of its hepatotoxicity. bered that zolpidem had been reintroduced because her Hepatoxicity has been suspected in association with zolpi- insomnia had recurred (she had taken 20 mg two days dem, but it has not been clearly established because of before the last acute episode). Viral hepatitis and concur- 34 concomitant drug treatment. We report a case of acute rent infections with Epstein-Barr virus and cytomegalovi- hepatitis mimicking biliary lithiasis after treatment with rus were excluded. No antibodies against smooth muscle, zolpidem alone at a therapeutic dose, with reappearance liver and kidney microsomes, or liver cytosol or mitochon- of the hepatoxicity after the drug was reintroduced. dria were detected in serum. Five months later the results A 53 year old woman was admitted in June 1997 for of liver function tests remained within normal limits and investigation of recurrent abdominal pain. -
HS 172 R5/13 Briefly Review the Objectives, Content and Activities of This Session
HS 172 R5/13 Briefly review the objectives, content and activities of this session. Upon successfully completing this session the participant will be able to: • Explain a brief history of the CNS Depressant category of drugs. • Identify common drug names and terms associated with this category. • Identify common methods of administration for this category. • Describe the symptoms, observable signs and other effects associated with this category. CONTENT SEGMENTS LEARNING ACTIVITIES A. Overview of the Category Instructor-Led Presentations B. Possible Effects Instructor Led Demonstrations C. OtdDtifEfftOnset and Duration of Effects RdiAiReading Assignmen ts D. Overdose Signs and Symptoms Video Presentations E. Expected Results of the Evaluation Slide Presentations F. Classification Exemplar HS 172 R5/13 9-2 • Explain the typical time parameters, i.e. onset and duration of effects, associated with this category. • List the clues that are likely to emerge when the drug influence evaluation is conducted for a person under the influence of this category of drugs. • Correctly answer the “topics for study” questions at the end of this session. HS 172 R5/13 9-3 A. Overview of the Category CNS Depressants Central Nervous System Depressants slow down the operations of the brain. Point out that other common names for CNS Depressants are “downers” and “sedative-hypnotics.” • Depressants first affect those arareaseas of the brain that control a person’ s conscious, voluntary actions. • Judgment, inhibitions and reaction time are some of the things that CNS Depressants affect first. • As the dose is increased, depressants begin to affect the parts of the brain that control the body’s automatic processes, heartbeat, respiration, etc. -
The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. -
Social Phobia and Personality Disorders: Comorbidity and Treatment Issues
Social phobia and personality disorders: comorbidity and treatment issues Van Velzen, Catharina, Johanna, Maria Social phobia and personality disorders: comorbidity and treatment issues/ Catharina, Johanna, Maria (Carol) van Velzen Thesis Groningen – With ref. – With summary in Dutch. ISBN: 90-901-5987-8 Subject headings: social phobia / personality disorder/ exposure in vivo/ comorbidity Cover design: Marbles on Ruby Red Carol van Velzen & Robert Mijdendorp Printed by: Grafisch centrum, Rijksuniversiteit Groningen RIJKSUNIVERSITEIT GRONINGEN Social Phobia and Personality Disorders: Comorbidity and Treatment Issues PROEFSCHRIFT ter verkrijging van het doctoraat in de Psychologische, Pedagogische en Sociologische Wetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op donderdag 12 september 2002 om 16.00 uur door Catharina Johanna Maria van Velzen geboren op 10 maart 1967 te Schipluiden Promotor : Prof. dr. P.M.G. Emmelkamp Co-promotor : Dr. A. Scholing Referent : Dr. F. Luteijn Beoordelingscommissie : Prof. dr. A.R. Arntz : Prof. dr. C.P.D.R. Schaap : Prof. dr. Ph. Spinhoven Dankwoord Bij mijn afscheid van de afdeling Klinische Psychologie, inmiddels alweer zeven jaar geleden, heb ik gezegd dat ik zeer veel geleerd had, zowel professioneel als persoonlijk, en dat niemand me dat meer kon afnemen, ook al zou het proefschrift er nooit komen. Nu kan ik zeggen: het proefschrift is er wel gekomen! Aan zowel dit resultaat als aan mijn “leerproces” hebben een groot aantal mensen een bijdrage geleverd. Dit is de plek om ze te bedanken. Allereerst wil ik Agnes Scholing en Paul Emmelkamp bedanken voor de eerste – prettige - kennismaking met het doen van onderzoek.