DOCSLIB.ORG

Inventory of the Most Important Pharmaceutical Compounds

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Inventory of the Most Important Pharmaceutical Compounds 018530 - SWITCH Sustainable Water Management in the City of the Future Integrated Project Global Change and Ecosystems Deliverable 4.1.2 Listing the most important pharmaceutical compounds from various therapeutic groups and the testing and validation of analytical methods for the selected compounds 4.1.2 A. Pre-selection of representative compounds for laboratory degradation tests 4.1.2 B Survey of the mostly used pharmaceutical compounds and hormones in the West Bank/Palestine 4.1.2 C. Estrogens in aquatic environment: A review. Due date of deliverable: 14 th February 2007 Actual submission date: 14 th February 2007 Start date of project: 1 February 2006 Duration: 60 months Authors : Katarzyna Kujawa-Roeleveld, Ime Akanyeti WU, Environmental Technology, Wageningen, The Netherlands Nidal Mahmoud, Water Studies Institute (WSI), Birzeit University, The West Bank, Palestine Wenxin Shi, IHE-UNESCO, Delft, The Netherlands Final Version Reviewer: Adriaan Mels Project co-funded by the European Commission within the Sixth Framework Programme (2002-2006) Dissemination Level PU Public Pu PP Restricted to other programme participants (including the Commission 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) 1 SWITCH Deliverable Briefing Note (months 0-12) SWITCH Document Deliverable 4.1.2 consists of three parts: (A) Pharmaceutical compounds in environment Pre-selection of representative compounds for laboratory degradation tests (B) Survey of the mostly used pharmaceutical compounds and hormones in the West Bank/ Palestine (C) Estrogens in aquatic environment: A review Audience This document is targeted at scientists, engineers and policy makers. Purpose The purpose of this document was to give: - a general overview on a variety and nature of human pharmaceutical compounds and their pathways into the environment; - a overview of the characteristics of the compounds in relation to their possible behaviour in a wastewater treatment system; - to make a pre-selection of a few representative compounds deserving special attention in further SWITCH laboratory research aiming at the removal potential of pharmaceutical compounds and their metabolites from concentrated domestic wastewater streams using proven biological, chemical-physical treatment technologies. Background Human pharmaceuticals are consumed in high quantities world wide; the consumption is in the range of tons per year per one pharmaceutical compound depending on the size of a country. The expectations are that these amounts will only keep increasing because of improving health care systems worldwide and longer life expectations of people. Conventional, sewer-based, sanitation systems are characterised by a high degree of dilution and many pharmaceutical compounds are not sufficiently removed. Discharge of these compound to surface water may form a threat to aquatic life and in the worst case may re-enter the water cycle through raw water intake from surface water or ground water. To minimise these risks source control is an interesting option. Applying separation of wastewater streams of different origin (black water, grey water) and their target treatment enables to keep pharmaceuticals concentrated in black water and urine and provide for effective removal. The reason that pharmaceutical compounds in the environment receive much attention is that they have been developed to perform a specific biological effect in human (and other) organisms. Next to, they possessed several common features like e.g. polarity or persistence to prevent their inactivation before they pose a therapeutic effect. This already indicates that if these substances are not eliminated prior to discharge they may enter aquatic and terrestrial ecosystems resulting in bioaccumulation and provoking environmental effects. The knowledge on the fate of pharmaceuticals during a variety of treatment technologies is, despite of significant scientific efforts, limited. To design an optimal treatment system that is able to eliminate the majority, if not all, of entering pharmaceutical micro-pollutants has not been possible yet. 2 Potential Impact Retrofit of existing treatment plants- or source control by implementation of source separated based sanitation system to remove human pharmaceutical would eliminate or minimize the potential risk of these compounds entering essential water resources, the risk of exposure of aquatic organisms to these micro-pollutants and the potential effect and accumulation of specific compounds in environment. Examples of proven effects have been already reported in different parts of the world. Since retrofit of the whole sanitation is not possible on a short term, the attention can focus in the first instance on significant point sources of emissions such as hospitals, nursery houses etc. For instance target treatment of (whole) hospital pharmaceuticals containing wastewater (black water = toilet water) would reduce total emission of certain, specific antibiotics even up to 80% (examples: Ampicillin, Penicillin G., Vancomycin). Issues - although the issue of the pharmaceuticals in the environment attracts a lot of attention, especially, of the scientific world. Within the EU there are no policies and standards yet that define which compounds should be removed and to which level. - analytical methods to determine pharmaceuticals in a complex matrix are complex, time-consuming and costly; for many pharmaceutical compounds they have not even been developed/validated yet - the fate of excretion, next to the parent compound, of (active) metabolites/conjugates in wastewater treatment systems is generally unclear. Recommendations The problem of pharmaceuticals in the environment requires wider recognition. Adequate measures are needed to minimize the emissions of human pharmaceuticals to the environment, such as: • technical (upgrading of existing treatment systems, • introduction of source separation and application of appropriate techniques for degradation of persistent pharmaceutical compounds, • on-site treatment for significant point sources like hospitals, elderly houses and • non-technical (increase public awareness, justified use of certain compound (e.g. avoid excessive use of anti-biotics and of very persistent pharmaceuticals), limit sell over the counter, etc.) For technical measures comprehensive knowledge on degradation and removal pathways (biological, chemical, physical) is necessary to establish. 3 Table of content Preface....................................................................................................................................................................6 1 Introduction ...................................................................................................................................................7 2 General characteristics of pharmaceuticals....................................................................................................8 3 Pharmaceutical metabolism and excretion...................................................................................................10 4 Sources of emission of pharmaceutical compounds ....................................................................................12 5 Variety of pharmaceutical compounds ........................................................................................................13 5.1 Group A: alimentary tract and metabolism .......................................................................................13 5.2 Group B: blood and blood forming organs........................................................................................13 5.3 Group C: cardiovascular system........................................................................................................13 5.4 Group J: antibiotics ...........................................................................................................................15 5.5 Group N: nervous system ..................................................................................................................15 5.6 Group pain relievers, antiphlogistics, analgesics, anti-inflammatories, non-steroidal drugs.............17 5.7 Group V: contrast media ...................................................................................................................18 6 Properties of pharmaceuticals......................................................................................................................19 7 Quantities of pharmaceuticals used (Dutch situation) .................................................................................21 8 Occurrence in aquatic environment .............................................................................................................25 8.1 Wastewater........................................................................................................................................25 8.2 Hospital wastewater ..........................................................................................................................25 8.3 Surface water.....................................................................................................................................25 8.4 Ground water.....................................................................................................................................27 8.5 Drinking water...................................................................................................................................27
Load more

Recommended publications
  • Additions and Deletions to the Drug Product List
    Prescription and Over-the-Counter Drug Product List 40TH EDITION Cumulative Supplement Number 09 : September 2020 ADDITIONS/DELETIONS FOR PRESCRIPTION DRUG PRODUCT LIST ACETAMINOPHEN; BUTALBITAL; CAFFEINE TABLET;ORAL BUTALBITAL, ACETAMINOPHEN AND CAFFEINE >A> AA STRIDES PHARMA 325MG;50MG;40MG A 203647 001 Sep 21, 2020 Sep NEWA ACETAMINOPHEN; CODEINE PHOSPHATE SOLUTION;ORAL ACETAMINOPHEN AND CODEINE PHOSPHATE >D> AA WOCKHARDT BIO AG 120MG/5ML;12MG/5ML A 087006 001 Jul 22, 1981 Sep DISC >A> @ 120MG/5ML;12MG/5ML A 087006 001 Jul 22, 1981 Sep DISC TABLET;ORAL ACETAMINOPHEN AND CODEINE PHOSPHATE >A> AA NOSTRUM LABS INC 300MG;15MG A 088627 001 Mar 06, 1985 Sep CAHN >A> AA 300MG;30MG A 088628 001 Mar 06, 1985 Sep CAHN >A> AA ! 300MG;60MG A 088629 001 Mar 06, 1985 Sep CAHN >D> AA TEVA 300MG;15MG A 088627 001 Mar 06, 1985 Sep CAHN >D> AA 300MG;30MG A 088628 001 Mar 06, 1985 Sep CAHN >D> AA ! 300MG;60MG A 088629 001 Mar 06, 1985 Sep CAHN ACETAMINOPHEN; HYDROCODONE BITARTRATE TABLET;ORAL HYDROCODONE BITARTRATE AND ACETAMINOPHEN >A> @ CEROVENE INC 325MG;5MG A 211690 001 Feb 07, 2020 Sep CAHN >A> @ 325MG;7.5MG A 211690 002 Feb 07, 2020 Sep CAHN >A> @ 325MG;10MG A 211690 003 Feb 07, 2020 Sep CAHN >D> AA VINTAGE PHARMS 300MG;5MG A 090415 001 Jan 24, 2011 Sep DISC >A> @ 300MG;5MG A 090415 001 Jan 24, 2011 Sep DISC >D> AA 300MG;7.5MG A 090415 002 Jan 24, 2011 Sep DISC >A> @ 300MG;7.5MG A 090415 002 Jan 24, 2011 Sep DISC >D> AA 300MG;10MG A 090415 003 Jan 24, 2011 Sep DISC >A> @ 300MG;10MG A 090415 003 Jan 24, 2011 Sep DISC >D> @ XIROMED 325MG;5MG A 211690
    [Show full text]
  • 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).
    [Show full text]
  • Comparison of the Anti-Inflammatory Effects of Cilomilast, Budesonide
    Ratcliffe and Dougall BMC Pharmacology and Toxicology 2012, 13:15 http://www.biomedcentral.com/2050-6511/13/15 RESEARCH ARTICLE Open Access Comparison of the anti-inflammatory effects of Cilomilast, Budesonide and a p38 Mitogen activated protein kinase inhibitor in COPD lung tissue macrophages Marianne Jennifer Ratcliffe1* and Iain Gordon Dougall2 Abstract Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by a largely irreversible airflow obstruction and a persistent, excessive inflammatory response. Alveolar macrophages (AMs) are increased in the lungs of COPD patients, and act as orchestrators of the inflammatory response, releasing a range of mediators to coordinate recruitment and activation of leukocytes. Attempts to treat the inflammatory component of COPD with anti-inflammatory drugs such as steroids has met with limited success. In this study, we compared the ability of the phosphodiesterase IV (PDEIV) inhibitor Cilomilast, the steroid Budesonide, and the p38 mitogen activated protein kinase inhibitor BIRB-796 to inhibit tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) releases from AMs isolated from COPD lung transplant tissue. All studies were carried out with appropriate ethical approval and written, informed consent was obtained from each subject. Cilomilast had little effect on cytokine release from AMs. There was considerable variability in the responsiveness of AMs to Budesonide, with a subset of AMs responding poorly to Budesonide. BIRB-796 inhibited TNFα release from all AM donors, including those that responded poorly to steroids. Treatment with BIRB-796 and Budesonide together gave an additive decrease in TNFa release. These results suggest that a p38 inhibitor may provide advantages over existing anti-inflammatory treatments for COPD, either as an add-on to existing therapy, or to treat patients who respond poorly to steroids.
    [Show full text]
  • Health Reports for Mutual Recognition of Medical Prescriptions: State of Play
    The information and views set out in this report are those of the author(s) and do not necessarily reflect the official opinion of the European Union. Neither the European Union institutions and bodies nor any person acting on their behalf may be held responsible for the use which may be made of the information contained therein. Executive Agency for Health and Consumers Health Reports for Mutual Recognition of Medical Prescriptions: State of Play 24 January 2012 Final Report Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Acknowledgements Matrix Insight Ltd would like to thank everyone who has contributed to this research. We are especially grateful to the following institutions for their support throughout the study: the Pharmaceutical Group of the European Union (PGEU) including their national member associations in Denmark, France, Germany, Greece, the Netherlands, Poland and the United Kingdom; the European Medical Association (EMANET); the Observatoire Social Européen (OSE); and The Netherlands Institute for Health Service Research (NIVEL). For questions about the report, please contact Dr Gabriele Birnberg ([email protected] ). Matrix Insight | 24 January 2012 2 Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Executive Summary This study has been carried out in the context of Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients’ rights in cross- border healthcare (CBHC). The CBHC Directive stipulates that the European Commission shall adopt measures to facilitate the recognition of prescriptions issued in another Member State (Article 11). At the time of submission of this report, the European Commission was preparing an impact assessment with regards to these measures, designed to help implement Article 11.
    [Show full text]
  • Guanidine-Containing Polyhydroxyl Macrolides: Chemistry, Biology, and Structure-Activity Relationship
    molecules Review Guanidine-Containing Polyhydroxyl Macrolides: Chemistry, Biology, and Structure-Activity Relationship Xiaoyuan Song 1, Ganjun Yuan 1,* , Peibo Li 2 and Sheng Cao 1 1 College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang 330045, China; [email protected] (X.S.); [email protected] (S.C.) 2 School of Life Sciences, Sun Yat-sen University, 135 Xingang Road, Guangzhou 510275, China; [email protected] * Correspondence: [email protected]; Tel.: +86-0791-83813459 Academic Editor: Jesus Simal-Gandara Received: 7 October 2019; Accepted: 29 October 2019; Published: 30 October 2019 Abstract: Antimicrobial resistance has been seriously threatening human health, and discovering new antimicrobial agents from the natural resource is still an important pathway among various strategies to prevent resistance. Guanidine-containing polyhydroxyl macrolides, containing a polyhydroxyl lactone ring and a guanidyl side chain, can be produced by many actinomycetes and have been proved to possess many bioactivities, especially broad-spectrum antibacterial and antifungal activities. To explore the potential of these compounds to be developed into new antimicrobial agents, a review on their structural diversities, spectroscopic characterizations, bioactivities, acute toxicities, antimicrobial mechanisms, and the structure-activity relationship was first performed based on the summaries and analyses of related publications from 1959 to 2019. A total of 63 guanidine-containing polyhydroxyl macrolides were reported, including
    [Show full text]
  • Mediated Pulmonary Hypertension in Neonatal Rats: a Role for Products of Lipid Peroxidation
    0031-3998/00/4803-0289 PEDIATRIC RESEARCH Vol. 48, No. 3, 2000 Copyright © 2000 International Pediatric Research Foundation, Inc. Printed in U.S.A. Endothelin-1 and O2-Mediated Pulmonary Hypertension in Neonatal Rats: A Role for Products of Lipid Peroxidation ROBERT P. JANKOV, XIAOPING LUO, JUDY CABACUNGAN, ROSETTA BELCASTRO, HELENA FRNDOVA, STEPHEN J. LYE, AND A. KEITH TANSWELL Medical Research Council Group in Lung Development and Lung Biology Programme [R.P.J., X.L., J.C., R.B., H.F., A.K.T.], Hospital for Sick Children Research Institute, the MRC Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital [S.J.L.], and the Departments of Obstetrics and Gynaecology [S.J.L.], Paediatrics [A.K.T.] and Physiology [A.K.T., S.J.L.], University of Toronto, Toronto, Ontario, M5S 1A8 Canada. ABSTRACT We hypothesized that reactive O2 species, or their interme- lung cell cultures. We conclude that reactive O2 species, or their diary products, generated during exposure to elevated O2 lead to bioactive intermediaries, are causative in O2-mediated pulmo- pathologic endothelin-1 expression in the newborn lung. Endo- nary hypertension and endothelin-1 up-regulation. It is likely that thelin-1 expression and 8-isoprostane content (an in vivo marker the bioactive lipid peroxidation product, 8-isoprostane, plays a of lipid peroxidation) were examined and found to be elevated key role in pathologic endothelin-1 expression and pulmonary (p Ͻ 0.05) in the lungs of newborn rats with abnormal lung hypertension during oxidant stress. (Pediatr Res 48: 289–298, morphology and pulmonary hypertension, as assessed by right 2000) ventricular hypertrophy, after a 14-d exposure to 60% O2.
    [Show full text]
  • Basic Concepts in Medicinal Chemistry, 2Nd Edition
    APP ANSWERS TO CHAPTER QUESTIONS CHAPTER 2 STRUCTURE ANALYSIS CHECKPOINT Checkpoint Drug 1: Venetoclax 1. Answers provided in table below. Functional Group Name Contribution to Water and/or Lipid Solubility A Halogen (chlorine atom) Lipid Solubility B Alicyclic ring, alkyl ring, cycloalkane Lipid Solubility C Tertiary amine (piperazine) Water Solubility D Heterocyclic ring system (pyrrolopyridine) Hydrocarbons: Lipid Solubility Nitrogen atoms: Water Solubility E Aromatic ring; phenyl ring; aromatic hydrocarbon Lipid Solubility F Sulfonamide Water Solubility G Secondary aromatic amine/aniline Water Solubility H Ether Hydrocarbons: Lipid Solubility Oxygen atom: Water Solubility 2. The sulfonamide and tertiary amine will be primarily ionized in most physiological environments and can participate in ion-dipole interactions (as the ion) with water. In the event that they are unionized, they could participate in hydrogen bonding interactions with water. The nitrogen atoms of the heterocyclic ring system, as well as the secondary aromatic amine, and the oxygen atom of the ether will not be appreciably ionized, but can participate in hydrogen bonding interactions with water. Thus, all of these functional groups contribute to the water solubility of venetoclax. The halogen as well as the hydrocarbon chains and rings are not able to ionize or form hydrogen bonds with water and thus contribute to the lipid solubility of venetoclax. 477 Unauthenticated | Downloaded 09/26/21 09:50 PM UTC 478 BASIC CONCEPTS IN MEDICINAL CHEMISTRY 3. Answers provided in table below. Electron Donating or Withdrawing Resonance or Induction A Electron Withdrawing Induction B Both Donates electrons into the aromatic ring through resonance. Withdraws electrons from adjacent methylene groups through induction.
    [Show full text]
  • Sustained-Release Compositions Containing Cation Exchange Resins and Polycarboxylic Polymers
    ~" ' Nil II II II II Ml Ml INI MINI II J European Patent Office *»%r\ n » © Publication number: 0 429 732 B1 Office_„. europeen des brevets © EUROPEAN PATENT SPECIFICATION © Date of publication of patent specification: 16.03.94 © Int. CI.5: A61 K 9/06, A61 K 9/1 8, A61 K 47/32 © Application number: 89312590.6 @ Date of filing: 01.12.89 © Sustained-release compositions containing cation exchange resins and polycarboxylic polymers. @ Date of publication of application: (73) Proprietor: ALCON LABORATORIES, INC. 05.06.91 Bulletin 91/23 6201 South Freeway Fort Worth Texas 76107(US) © Publication of the grant of the patent: 16.03.94 Bulletin 94/11 @ Inventor: Janl, Rajni 4621 Briarhaven Road © Designated Contracting States: Fort Worth, Texas 76109(US) AT BE CH DE FR GB IT LI LU NL SE Inventor: Harris, Robert Gregg 3224 Westcliff Road W. © References cited: Fort Worth, Texas 76109(US) EP-A- 0 254 822 J.Pharm. SCI., vol. 60, no. 9, September 1971, © Representative: Jump, Timothy John Simon et pages 1343-1345 A. HEYD:"Polymer-drug in- al teraction: stability of aqueous gels contain- Venner Shipley & Co. ing neomycin sulfate" 20 Little Britain London EC1A 7DH (GB) 00 CM CO o> CM Note: Within nine months from the publication of the mention of the grant of the European patent, any person ® may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition CL shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee LU has been paid (Art.
    [Show full text]
  • Educationally Intervening the Use of Potentially Harmful Medication Among Residents in Institutional Settings
    Department of General Practice and Primary Health Care Faculty of Medicine University of Helsinki Finland EDUCATIONALLY INTERVENING THE USE OF POTENTIALLY HARMFUL MEDICATION AMONG RESIDENTS IN INSTITUTIONAL SETTINGS Anna-Liisa Juola Academic dissertation To be presented, with the permission of the Faculty of Medicine, University of Helsinki, for public examination in Auditorium XII, Fabianinkatu 33, on 2nd February 2018, at 12 noon Helsinki, Finland 2018 Supervisors Professor Kaisu Pitkälä, MD, PhD University of Helsinki, Department of General Practice and Primary Health Care Helsinki, Finland Mikko Björkman, MD, PhD University of Helsinki, Department of Medicine, Division of Geriatrics Helsinki, Finland Reviewers Professor Esa Leinonen, MD, PhD University of Tampere, Department of Psychiatry Tampere, Finland Adjunct Professor Juha Puustinen, MD, PhD University of Helsinki, Division of Pharmacology and Pharmacotherapy Helsinki, Finland Satakunta Hospital District, Unit of Neurology Pori, Finland Opponent Adjunct Professor Raimo Isoaho, MD, MPH, PhD University of Turku, Department of General Practice Turku, Finland City of Vaasa, Social and Health Services Vaasa, Finland Cover graphics Vesa Juola Untitled 2017 ISBN 978-951-51-4032-6 (nid.) ISBN 978-951-51-4033-3 (PDF) Unigrafia Helsinki 2018 To Vesa with love Contents Abbreviations 7 Definitions 8 List of original publications 9 Abstract 10 Tiivistelmä (Finnish Abstract) 13 1 Introduction 17 2 Review of the literature 19 2.1 Ageing and medication 19 2.1.1 Pharmacokinetics
    [Show full text]
  • Drug and Medication Classification Schedule
    KENTUCKY HORSE RACING COMMISSION UNIFORM DRUG, MEDICATION, AND SUBSTANCE CLASSIFICATION SCHEDULE KHRC 8-020-1 (11/2018) Class A drugs, medications, and substances are those (1) that have the highest potential to influence performance in the equine athlete, regardless of their approval by the United States Food and Drug Administration, or (2) that lack approval by the United States Food and Drug Administration but have pharmacologic effects similar to certain Class B drugs, medications, or substances that are approved by the United States Food and Drug Administration. Acecarbromal Bolasterone Cimaterol Divalproex Fluanisone Acetophenazine Boldione Citalopram Dixyrazine Fludiazepam Adinazolam Brimondine Cllibucaine Donepezil Flunitrazepam Alcuronium Bromazepam Clobazam Dopamine Fluopromazine Alfentanil Bromfenac Clocapramine Doxacurium Fluoresone Almotriptan Bromisovalum Clomethiazole Doxapram Fluoxetine Alphaprodine Bromocriptine Clomipramine Doxazosin Flupenthixol Alpidem Bromperidol Clonazepam Doxefazepam Flupirtine Alprazolam Brotizolam Clorazepate Doxepin Flurazepam Alprenolol Bufexamac Clormecaine Droperidol Fluspirilene Althesin Bupivacaine Clostebol Duloxetine Flutoprazepam Aminorex Buprenorphine Clothiapine Eletriptan Fluvoxamine Amisulpride Buspirone Clotiazepam Enalapril Formebolone Amitriptyline Bupropion Cloxazolam Enciprazine Fosinopril Amobarbital Butabartital Clozapine Endorphins Furzabol Amoxapine Butacaine Cobratoxin Enkephalins Galantamine Amperozide Butalbital Cocaine Ephedrine Gallamine Amphetamine Butanilicaine Codeine
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,828,437 B2 Sundberg Et Al
    USOO8828437B2 (12) United States Patent (10) Patent No.: US 8,828,437 B2 Sundberg et al. (45) Date of Patent: *Sep. 9, 2014 (54) THERMOGELLING ANAESTHETIC USPC .......................................................... 424/484 COMPOSITIONS (58) Field of Classification Search None (71) Applicant: Pharmanest AB, Solna (SE) See application file for complete search history. (72) Inventors: Mark Sundberg, Arsta (SE); Arne (56) References Cited Brodin, Sodertalje (SE); Nils Kallberg, Taby (SE) U.S. PATENT DOCUMENTS (73) Assignee: Pharmanest AB, Solna (SE) 8,663,688 B2* 3/2014 Fernandez et al. ............ 424/487 2004/O220283 A1 11/2004 Zhang et al. 2005/0O27.019 A1 2/2005 Zhang et al. (*) Notice: Subject to any disclaimer, the term of this 2007/0298.005 A1 12, 2007 Thibault patent is extended or adjusted under 35 2008. O15421.0 A1 6/2008 Jordan et al. U.S.C. 154(b) by 0 days. 2012fO294907 A1 11/2012 Zhang et al. This patent is Subject to a terminal dis claimer. FOREIGN PATENT DOCUMENTS AU 2006201233 B2 10, 2007 (21) Appl. No.: 14/172,794 EP O517160 A1 12, 1992 EP 1629852 A2 3, 2006 (22) Filed: Feb. 4, 2014 KR 2002OO13248 A 2, 2002 (65) Prior Publication Data (Continued) OTHER PUBLICATIONS US 2014/O155.434 A1 Jun. 5, 2014 Written Opinion, Intellectual Property Office of Singapore, from the Related U.S. Application Data corresponding Singapore Application No. 201206824-3, Jul. 19. (63) Continuation of application No. 13/638.511, filed as 2013. application No. PCT/EP2011/055009 on Mar. 31, Notification of First Office Action, China Intellectual Property 2011. Office, from the corresponding Chinese Application No.
    [Show full text]
  • 2-Adrenergic Receptor Is Determined by Conformational Equilibrium in the Transmembrane Region
    ARTICLE Received 21 Mar 2012 | Accepted 2 Aug 2012 | Published 4 Sep 2012 DOI: 10.1038/ncomms2046 Efficacy of theβ 2-adrenergic receptor is determined by conformational equilibrium in the transmembrane region Yutaka Kofuku1,2, Takumi Ueda1, Junya Okude1, Yutaro Shiraishi1, Keita Kondo1, Masahiro Maeda3, Hideki Tsujishita3 & Ichio Shimada1,4 Many drugs that target G-protein-coupled receptors (GPCRs) induce or inhibit their signal transduction with different strengths, which affect their therapeutic properties. However, the mechanism underlying the differences in the signalling levels is still not clear, although several structures of GPCRs complexed with ligands determined by X-ray crystallography are available. Here we utilized NMR to monitor the signals from the methionine residue at position 82 in neutral antagonist- and partial agonist-bound states of β2-adrenergic receptor (β2AR), which are correlated with the conformational changes of the transmembrane regions upon activation. We show that this residue exists in a conformational equilibrium between the inverse agonist- bound states and the full agonist-bound state, and the population of the latter reflects the signal transduction level in each ligand-bound state. These findings provide insights into the multi-level signalling of β2AR and other GPCRs, including the basal activity, and the mechanism of signal transduction mediated by GPCRs. 1 Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. 2 Japan Biological Informatics Consortium (JBIC), Tokyo 135-0064, Japan. 3 Shionogi Co., Ltd., Discovery Research Laboratories, Osaka 561-0825, Japan. 4 Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), Aomi 2-41-6, Koto-ku, Tokyo 135-0064, Japan.
    [Show full text]