DOCSLIB.ORG

Grastilleur Sebastien Phd 2019.Pdf (10.90Mb)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Grastilleur Sebastien Phd 2019.Pdf (10.90Mb) Université de Sherbrooke Caractérisation de l’internalisation constitutive du récepteur aux opioïdes de type delta Par Sébastien Grastilleur Programme de physiologie Thèse présentée à la Faculté de médecine et des sciences de la santé en vue de l’obtention du grade de philosophiae doctor (Ph.D.) en physiologie Sherbrooke, Québec, Canada Novembre, 2019 Membres du jury d’évaluation Ahmed Chraïbi Ph.D; Programme de physiologie, président du jury Louis Gendron Ph.D; Programme de physiologie, directeur de recherche Christine Lavoie Ph.D; Programme de pharmacologie, co-directrice de recherche Stéphane Laporte Ph.D; Department of Endocrinology & Metabolism, McGill University, évaluateur externe à l’Université de Sherbrooke Steve Jean Ph.D; Département d’anatomie, évaluateur externe au programme © Grastilleur Sébastien, 2019 À mes proches et à Valmy Vérité. « Impossible est un mot difficile à prononcer pour un scientifique ». Yves Coppens iii Résumé Caractérisation de l’internalisation constitutive du récepteur aux opioïdes de type delta Par Sébastien Grastilleur Programme de physiologie Thèse présentée à la Faculté de médecine et des sciences de la santé en vue de l’obtention du diplôme de philosophiae doctor (Ph.D.) en physiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada, J1H 5N4 Le récepteur opioïde delta (DOP), un récepteur couplé aux protéines G (RCPG), est impliqué dans la régulation de nombreux processus physiologiques et physiopathologiques (nociception, anxiété, dépression, etc.). En ce sens, il suscite de plus en plus d’intérêt de la part du milieu académique et des compagnies pharmaceutiques. DOP est exprimé de façon ubiquitaire mais est essentiellement présent à l’intérieur des cellules avec une faible expression à la surface cellulaire. Cette localisation particulière pourrait expliquer pourquoi les agonistes du DOP génèrent peu d'effets analgésiques in vivo. Toutefois, il est possible sous certaines conditions (inflammation ou traitement chronique à la morphine) de potentialiser les effets de ces agonistes chez l’animal. Ces effets s’accompagnent d’une augmentation de la densité du récepteur à la surface des cellules. Bien que DOP soit internalisé suivant son activation par un agoniste, il a été observé qu’il était également constitutivement internalisé dans les cellules. Cependant, la caractérisation et régulation de cette voie d’internalisation de DOP est encore peu décrite. Dans le cadre de mes travaux, nous proposons l’hypothèse que l’internalisation constitutive serait un mécanisme capable de moduler l’expression de DOP à la surface cellulaire. Dans des cellules HEK293, exprimant de façon stable Flag DOP, nous avons tout d’abords confirmé l’internalisation constitutive du récepteur. Des expériences d'immunofluorescences avec des marqueurs de Rab ont montré qu’après son internalisation, DOP colocaliserait avec des marqueurs d’endosome précoce Rab5 et de recyclage rapide Rab4. De plus, des co-immunoprécipitations ont révélé une possible interaction entre DOP et ces Rab. D’autre part, l’utilisation d’un mutant inactif de Rab5 a montré une altération de l’internalisation du DOP. Ces résultats suggèrent que l’internalisation constitutive du DOP serait Rab5-dépendante. Enfin, les niveaux de DOP à la surface des cellules ont été diminués à la suite de la déplétion de Rab4A par un DsiARN, suggérant un recyclage constitutif Rab4- dépendant. La déplétion de Rab4A atténuerait également la signalisation du DOP à la suite de son activation par un agoniste. En parallèle, pour identifier de nouveaux partenaires d’interaction du DOP, nous avons utilisé la technologie de biotinylation de proximité (Bio- ID) par la biotine ligase BirA*. De nombreux candidats ont pu ainsi être identifiés. À plus long terme, nos résultats pourraient permettre le développement de nouvelles stratégies pour limiter l’internalisation ou augmenter le recyclage constitutif du DOP. Cela permettrait d’augmenter les niveaux membranaires du DOP et ainsi potentialiser les effets des agonistes delta dans le traitement de pathologies, incluant le traitement de la douleur. Mots clés : DOP, Rab5, Rab4, internalisation et recyclage constitutif, Bio-ID. iv Summary Characterization of delta opioid receptor, DOP, constitutive internalization By Sébastien Grastilleur Physiology program Thesis presented at the Faculty of medicine and health sciences for the obtention of Doctor degree diploma philosophiae doctor (Ph.D.) in physiology, Faculty of medicine and health sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada, J1H 5N4 The delta opioid receptor (DOP), a G protein-coupled receptor (GPCR) is involved in the regulation of many physiological and physio-pathological processes (nociception, stress response, neuroprotection, neurodegenerative diseases, anxiety, depression, etc.) and thus raises more and more interest from academia and pharmaceutical companies. DOP is ubiquitously expressed but mainly localized to intracellular sites, with only a small subset expressed at the cell surface. This specific localization could explain why DOP agonists generate few analgesics effects in vivo. On the other hand, it is possible, under certain conditions (inflammation or chronic treatment with morphine) to potentiate the effects of DOP agonists in animals. This effect was paralleled by an increased density of DOP at the plasma membrane. In addition to the agonist-induced internalization, DOP was previously shown to be constitutively internalized. However, the mechanisms involved in this internalization pathway of DOP is still poorly characterized. In the current study, we investigated and characterized the constitutive internalization of DOP as a potential mechanism controlling its cell surface expression. In HEK293 cells stably expressing Flag-tagged DOP, we first confirmed that DOP is constitutively internalized. Immunofluorescence experiments with selected Rab protein markers indicated that internalized DOP was mainly co-localized with the early endosome marker Rab5 and the rapid recycling endosome marker Rab4. Co-immunoprecipitation assays revealed a potential interaction between DOP and these two Rab proteins. Transfection with Rab5 dominant negative mutant inhibits the internalization of DOP. These results indicate that constitutive endocytosis is Rab5-dependent. Furthermore, DOP cell surface expression was strongly reduced following Rab4A DsiRNA treatment, indicating that DOP constitutive recycling is Rab4-dependent. Rab4A depletion also attenuates agonist-induced DOP signaling. In parallel, we used a proximity-dependent biotinylation (Bio-ID) approach with BirA* to identify novel partners of DOP. Many candidates have been identified. In the long term, our results could allow the development of new strategies to limit constitutive internalization or increase constitutive recycling of DOP. This would increase the cell-surface levels of DOP and thus potentiate the effects of DOP agonists in the treatment of pathologies, including pain management. Keywords: DOP, Rab5, Rab4, constitutive internalization and recycling, Bio-ID. v TABLE DES MATIERES Résumé .................................................................................................................................. iv Summary ................................................................................................................................ v Liste des figures ..................................................................................................................... x Liste des tableaux ................................................................................................................. xi Liste des abréviations ........................................................................................................ xii Introduction ........................................................................................................................... 1 Le système opioïdergique. ................................................................................................ 2 Les récepteurs couplés aux protéines G (RCPG). .......................................................... 2 Les protéines G hétérotrimériques. ................................................................................. 4 Les protéines Gαs. ......................................................................................................... 6 Les protéines Gαi. ......................................................................................................... 7 Les protéines Gαq. ......................................................................................................... 7 Les protéines Gα12/13. .................................................................................................... 8 Le complexe Gβγ. .......................................................................................................... 8 Les récepteurs aux opioïdes. ............................................................................................ 9 Le récepteur mu, MOP. .............................................................................................. 11 Le récepteur kappa, KOP. ......................................................................................... 12 Le récepteur delta, DOP. ............................................................................................ 13 Régulation du récepteur aux opioïdes de type delta, DOP. ........................................ 16 Modifications
Load more

Recommended publications
  • (Ph OH N N Me O YO O YO
    US 20070265293A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0265293 A1 Boyd et al. (43) Pub. Date: Nov. 15, 2007 (54) (S)-N-METHYLNALTREXONE Publication Classification (76) Inventors: Thomas A. Boyd, Grandview, NY (51) Int. Cl. (US); Howard Wagoner, Warwick, NY A6II 3L/4355 (2006.01) (US); Suketu P. Sanghvi, Kendall Park, A6M II/00 (2006.01) NJ (US); Christopher Verbicky, A6M I5/08 (2006.01) Broadalbin, NY (US); Stephen 39t. 35O C Andruski, Clifton Park, NY (US) (2006.01) A6IP 3L/00 (2006.01) Correspondence Address: St. 4. CR WOLF GREENFIELD & SACKS, P.C. (2006.01) 6OO ATLANTIC AVENUE 3G (i. 308: BOSTON, MA 02210-2206 (US) A6IP 33/02 (2006.01) C07D 489/00 (2006.01) (21) Appl. No.: 11/441,452 (52) U.S. Cl. .............. 514/282; 128/200.23; 128/202.17; (22) Filed: May 25, 2006 546/45 Related U.S. Application Data (57) ABSTRACT This invention relates to S-MNTX, methods of producing (60) Provisional application No. 60/684,570, filed on May S-MNTX, pharmaceutical preparations comprising 25, 2005. S-MNTX and methods for their use. O G M Br Br e (pH OH N N Me O YO O YO OH OH R-MNTX S-MNTX Patent Application Publication Nov. 15, 2007 Sheet 1 of 6 US 2007/0265293 A1 Fig. 1 OH OH Me-N Me-N D / O O -----BBr, O O CHCI NMP, 3 AUTOCLAVE, 70'C OMe OH 1 2 Br OH As GE) G As 69 GOH Me-N ION Me-N -lass O SO EXCHANGE O SO OH OH 3 S-MNTX 1 - OXYCODONE 2 - OXYMORPHONE 3 - ODIDE SALT OF S-MNTX Fig.
    [Show full text]
  • The Organic Chemistry of Drug Synthesis
    THE ORGANIC CHEMISTRY OF DRUG SYNTHESIS VOLUME 3 DANIEL LEDNICER Analytical Bio-Chemistry Laboratories, Inc. Columbia, Missouri LESTER A. MITSCHER The University of Kansas School of Pharmacy Department of Medicinal Chemistry Lawrence, Kansas A WILEY-INTERSCIENCE PUBLICATION JOHN WILEY AND SONS New York • Chlchester • Brisbane * Toronto • Singapore Copyright © 1984 by John Wiley & Sons, Inc. All rights reserved. Published simultaneously in Canada. Reproduction or translation of any part of this work beyond that permitted by Section 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to the Permissions Department, John Wiley & Sons, Inc. Library of Congress Cataloging In Publication Data: (Revised for volume 3) Lednicer, Daniel, 1929- The organic chemistry of drug synthesis. "A Wiley-lnterscience publication." Includes bibliographical references and index. 1. Chemistry, Pharmaceutical. 2. Drugs. 3. Chemistry, Organic—Synthesis. I. Mitscher, Lester A., joint author. II. Title. [DNLM 1. Chemistry, Organic. 2. Chemistry, Pharmaceutical. 3. Drugs—Chemical synthesis. QV 744 L473o 1977] RS403.L38 615M9 76-28387 ISBN 0-471-09250-9 (v. 3) Printed in the United States of America 10 907654321 With great pleasure we dedicate this book, too, to our wives, Beryle and Betty. The great tragedy of Science is the slaying of a beautiful hypothesis by an ugly fact. Thomas H. Huxley, "Biogenesis and Abiogenisis" Preface Ihe first volume in this series represented the launching of a trial balloon on the part of the authors. In the first place, wo were not entirely convinced that contemporary medicinal (hemistry could in fact be organized coherently on the basis of organic chemistry.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley Et Al
    US 2014O144429A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley et al. (43) Pub. Date: May 29, 2014 (54) METHODS AND DEVICES FOR COMPOUND (60) Provisional application No. 61/887,045, filed on Oct. DELIVERY 4, 2013, provisional application No. 61/831,992, filed on Jun. 6, 2013, provisional application No. 61/794, (71) Applicant: E-NICOTINE TECHNOLOGY, INC., 601, filed on Mar. 15, 2013, provisional application Draper, UT (US) No. 61/730,738, filed on Nov. 28, 2012. (72) Inventors: Martin Wensley, Los Gatos, CA (US); Publication Classification Michael Hufford, Chapel Hill, NC (US); Jeffrey Williams, Draper, UT (51) Int. Cl. (US); Peter Lloyd, Walnut Creek, CA A6M II/04 (2006.01) (US) (52) U.S. Cl. CPC ................................... A6M II/04 (2013.O1 (73) Assignee: E-NICOTINE TECHNOLOGY, INC., ( ) Draper, UT (US) USPC ..................................................... 128/200.14 (21) Appl. No.: 14/168,338 (57) ABSTRACT 1-1. Provided herein are methods, devices, systems, and computer (22) Filed: Jan. 30, 2014 readable medium for delivering one or more compounds to a O O Subject. Also described herein are methods, devices, systems, Related U.S. Application Data and computer readable medium for transitioning a Smoker to (63) Continuation of application No. PCT/US 13/72426, an electronic nicotine delivery device and for Smoking or filed on Nov. 27, 2013. nicotine cessation. Patent Application Publication May 29, 2014 Sheet 1 of 26 US 2014/O144429 A1 FIG. 2A 204 -1 2O6 Patent Application Publication May 29, 2014 Sheet 2 of 26 US 2014/O144429 A1 Area liquid is vaporized Electrical Connection Agent O s 2.
    [Show full text]
  • ATP, 489 Absolute Configuration Benzomotphans, 204 Levotphanol
    Index AIDA, 495 Affinity labeling, analogs of (Cont.) cAMP, 409, 489 motphine,448 ATP, 409, 489 naltrexone, 449 [3H] ATP, 489 norlevotphanol,449 Absolute configuration normetazocine, 181 benzomotphans, 204 norpethidine, 232 levotphanol, 115 oripavine, 453 methadone and analogs, 316 oxymotphone, 449 motphine, 86 K-Agonists, 179,405,434 phenoperidine, 234 Aid in Interactive Drug Analysis, 495 piperazine derivatives, 399 [L-Ala2] dermotphin, 363 prodines and analogs, 272 [D-Ala, D-Leu] enkephalin (DADL), 68, 344 sinomenine, 28, 115 [D-Ala2 , Bugs] enkephalinamide, 347, 447 viminol, 400 [D-Ala2, Met'] enkephalinamide, 337, 346, Ac 61-91,360 371,489 Acetylcholine, 5, 407 [D-Ala2]leu-enkephalin, 344, 346, 348 Acetylcholine analogs, 186, 191 [D-Ala2] met-enkephalin, 348 l-Acetylcodeine, 32 [D-Ala2] enkephalins, 347 Acetylmethadols (a and (3) Alfentanil, 296 maintenance of addicts by a-isomer, 304, 309 (±)-I1(3-Alkylbenzomotphans, 167, 170 metabolism, 309 11(3-Alkylbenzomotphans, 204 N-allyl and N-CPM analogs, 310, 431 7-Alkylisomotphinans, 146 stereochemistry, 323 N-Alkylnorketobemidones, 431 synthesis, 309 N-Alkylnorpethidines, 233 X-ray crystallography, 327 N-Allylnormetazocine, 420 6-Acetylmotphine, receptor binding, 27 N-Allylnormotphine, 405 Acetylnormethadol, 323 N-Allylnorpethidine, 233 8(3-Acyldihydrocodeinones, 52 3-Allylprodines (a and (3), 256 14-Acyl-4,5-epoxymotphinans, 58 'H-NMR and stereochemistry, 256 7-Acylhydromotphones, 128 X-ray crystallography, 256 Addiction, 4 N-Allylnormetazocine, 420 Adenylate cyclase, 6, 409, 413, 424,
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • (S)-N-Methylnaltrexone
    (19) & (11) EP 2 450 360 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 09.05.2012 Bulletin 2012/19 C07D 489/08 (2006.01) A61K 31/485 (2006.01) A61P 1/12 (2006.01) A61P 25/04 (2006.01) (21) Application number: 11180242.7 (22) Date of filing: 25.05.2006 (84) Designated Contracting States: • Sanghvi, Suketu. P AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Kendall Park, NJ New Jersey 18824 (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Boyd, Thomas. A SK TR Grandview, NY New York 10960 (US) • Verbicky, Christopher (30) Priority: 25.05.2005 US 684570 P Broadalbin, NY New York 12025 (US) • Andruski, Stephen (62) Document number(s) of the earlier application(s) in Clifton Park, NY New York 12065 (US) accordance with Art. 76 EPC: 06771162.2 / 1 928 882 (74) Representative: Jump, Timothy John Simon et al Venner Shipley LLP (71) Applicant: Progenics Pharmaceuticals, Inc. 200 Aldersgate Tarrytown, NY 10591 (US) London EC1A 4HD (GB) (72) Inventors: • Wagoner, Howard Warwick, NY New York 10990 (US) (54) (S)-N-Methylnaltrexone (57) This invention relates to S-MNTX, methods of producing S-MNTX, pharmaceutical preparations comprising S- MNTX and methods for their use. EP 2 450 360 A2 Printed by Jouve, 75001 PARIS (FR) EP 2 450 360 A2 Description FIELD OF THE INVENTION 5 [0001] This invention relates to (S)-N-methylnaltrexone (S-MNTX), stereoselective synthetic methods for the prepa- ration of S-MNTX, pharmaceutical preparations comprising S-MNTX and methods for their use.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • WO 2009/143297 Al
    (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 26 November 2009 (26.11.2009) WO 2009/143297 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every AOlN 57/00 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, PCT/US2009/044746 EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (22) International Filing Date: HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, 20 May 2009 (20.05.2009) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, (25) Filing Language: English NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, (26) Publication Language: English SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/054,765 20 May 2008 (20.05.2008) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): NEU- GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ROGESX, INC. [US/US]; 2215 Bridgepointe Parkway, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Suite 200, San Mateo, CA 94404 (US).
    [Show full text]
  • List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify
    List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify, abnormal basal ganglia function, abuse of medicines, Aceperone, Acepromazine, Aceprometazine, Acetildenafil, Aceto phenazine, Acetoxy Dipt, Acetyl morphone, Acetyl propionyl morphine, Acetyl psilocin, Activation syndrome, acute anxiety, acute hypertension, acute panic attacks, Adderall, Addictions to drugs, Addictions to medicines, Addictions to substances, Adrenorphin, Adverse effects of psychoactive drugs, adverse reactions to medicines, aggression, aggressive, aggressiveness, agitated depression, Agitation and restlessness, Aildenafil, Akuammine, alcohol abuse, alcohol addiction, alcohol withdrawl, alcohol-related brain damage, alcohol- related liver damage, alcohol mix with medicines for adverse reaction, Alcoholism, Alfetamine, Alimemazine, Alizapride, Alkyl nitrites, allergic breathing reactions to meds, choking to anaphallectic shock, & death; allergic skin reactions to meds, rash, itchyness, hives, welts, etc, Alletorphine, Almorexant, Alnespirone, Alpha Ethyltryptamine, Alpha Neoendorphin, alterations in brain hormones, alterations in mental status, altered consciousness, altered mind, Altoqualine, Alvimopan, Ambien, Amidephrine, Amidorphin, Amiflamine, Amisulpride, Amphetamines, Amyl nitrite, Anafranil, Analeptic, Anastrozole, Anazocine, Anilopam, Antabuse, anti anxiety meds, anti dopaminergic activity, anti seizure meds, Anti convulsants, Anti depressants, Anti emetics, Anti histamines, anti manic meds, anti parkinsonics, Anti psychotics, Anxiety disorders,
    [Show full text]
  • Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes
    Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 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. Product CAS No. Product CAS No. ABACAVIR 136470-78-5 ACEXAMIC ACID 57-08-9 ABAFUNGIN 129639-79-8 ACICLOVIR 59277-89-3 ABAMECTIN 65195-55-3 ACIFRAN 72420-38-3 ABANOQUIL 90402-40-7 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABCIXIMAB 143653-53-6 ACITEMATE 101197-99-3 ABECARNIL 111841-85-1 ACITRETIN 55079-83-9 ABIRATERONE 154229-19-3 ACIVICIN 42228-92-2 ABITESARTAN 137882-98-5 ACLANTATE 39633-62-0 ABLUKAST 96566-25-5 ACLARUBICIN 57576-44-0 ABUNIDAZOLE 91017-58-2 ACLATONIUM NAPADISILATE 55077-30-0 ACADESINE 2627-69-2 ACODAZOLE 79152-85-5 ACAMPROSATE 77337-76-9 ACONIAZIDE 13410-86-1 ACAPRAZINE 55485-20-6 ACOXATRINE 748-44-7 ACARBOSE 56180-94-0 ACREOZAST 123548-56-1 ACEBROCHOL 514-50-1 ACRIDOREX 47487-22-9 ACEBURIC ACID 26976-72-7
    [Show full text]
  • (12) United States Patent (Lo) Patent No.: US 8,480,637 B2
    111111111111111111111111111111111111111111111111111111111111111111111111 (12) United States Patent (lo) Patent No.: US 8,480,637 B2 Ferrari et al. (45) Date of Patent : Jul. 9, 2013 (54) NANOCHANNELED DEVICE AND RELATED USPC .................. 604/264; 907/700, 902, 904, 906 METHODS See application file for complete search history. (75) Inventors: Mauro Ferrari, Houston, TX (US); (56) References Cited Xuewu Liu, Sugar Land, TX (US); Alessandro Grattoni, Houston, TX U.S. PATENT DOCUMENTS (US); Daniel Fine, Austin, TX (US); 5,651,900 A 7/1997 Keller et al . .................... 216/56 Randy Goodall, Austin, TX (US); 5,728,396 A 3/1998 Peery et al . ................... 424/422 Sharath Hosali, Austin, TX (US); Ryan 5,770,076 A 6/1998 Chu et al ....................... 210/490 5,798,042 A 8/1998 Chu et al ....................... 210/490 Medema, Pflugerville, TX (US); Lee 5,893,974 A 4/1999 Keller et al . .................. 510/483 Hudson, Elgin, TX (US) 5,938,923 A 8/1999 Tu et al . ........................ 210/490 5,948,255 A * 9/1999 Keller et al . ............. 210/321.84 (73) Assignees: The Board of Regents of the University 5,985,164 A 11/1999 Chu et al ......................... 516/41 of Texas System, Austin, TX (US); The 5,985,328 A 11/1999 Chu et al ....................... 424/489 Ohio State University Research (Continued) Foundation, Columbus, OH (US) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this WO WO 2004/036623 4/2004 WO WO 2006/113860 10/2006 patent is extended or adjusted under 35 WO WO 2009/149362 12/2009 U.S.C. 154(b) by 612 days.
    [Show full text]
  • Benefits and Risks of Pharmaceutical Opioids
    Benefits and risks of pharmaceutical opioids: Essential treatment and diverted medication A global review of availability, extra-medical use, injection and the association with HIV Louisa Degenhardt, Briony Larance, Bradley Mathers, Tasnim Azim, Adeeba Kamarulzaman, Richard Mattick, Samiran Panda, Abdalla Toufik, Mark Tyndall, Lucas Wiessing and Alex Wodak on behalf of the Reference Group to the United Nations on HIV and injecting drug use National Drug and Alcohol Research Centre UNIVERSITY OF NEW SOUTH WALES Sydney, Australia i ISBN: 978-0-7334-2707-7 This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use or use within your organisation. All other rights are reserved. Requests and enquiries concerning reproduction and rights should be addressed to the information manager, National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052, Australia. ii Acknowledgements This report is a product of the Reference Group to the United Nations on HIV and injecting drug use and was reviewed by the 2007 members of the Reference Group and also the Secretariat of the Reference Group. In 2007 the Reference Group members were Tasnim Azim, Mauro Guarinieri, Matthew Hickman, Adeeba Kamarulzaman, Kasia Malinowska-Sempruch, Fabio Mesquita, Azarakhsh Mokri, Olanrewaju Olusola Onigbogi, Fred Owiti, Samiran Panda, Steffanie A. Strathdee, Fayzal Sulliman, Abdalla Toufik, Jallal Toufiq, Mark Tyndall and Lucas Wiessing. In 2007 the Secretariat consisted of Richard Mattick, Louisa Degenhardt, Bradley Mathers, Benjamin Phillips, Kate Dolan and Alex Wodak. The following individuals assisted with the compilation of the literature: • Laura Kemmis, United Kingdom • Gabrielle Campbell, NDARC, University of NSW • Eva Congreve, NDARC, University of NSW • Benjamin Phillips, NDARC, University of NSW • Jessica Singleton, NDARC.
    [Show full text]