DOCSLIB.ORG

Determination of the Receptor Selectivity of Opioid Agonists in The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Determination of the Receptor Selectivity of Opioid Agonists in The Br. J. Pharmac. (1985), 86, 899-904 Determination ofthe receptor selectivity of opioid agonists in the guinea-pig ileum and mouse vas deferens by use of 3-funaltrexamine A.G. Hayes, M.J. Sheehan & M.B. Tyers Department ofNeuropharmacology, Glaxo Group Research Ltd, Ware, Herts 1 The irreversible inhibitor of p-opioid receptor-mediated effects, P-funaltrexamine (P-FNA), was used to investigate the selectivity of various opioid agonists at gi-opioid receptors in the electrically stimulated guinea-pig ileum and mouse vas deferens preparations in vitro. 2 In the guinea-pig ileum, pretreatment with P-FNA (3 x 10-8-3 x 10-6M) produced a concentra- tion-dependent antagonism of the inhibitory effect produced by the pt-opioid receptor agonist [D-Ala2, MePhe4, Gly(ol)5]enkephalin (DAGO). High concentrations of P-FNA (3 x 10-6_ X 10-5M) also antagonized the inhibitory effects of the c-opioid agonist U50488. 3 Pretreatment of guinea-pig ileum with P-FNA at I x 10-6M resulted in blockade of the effect of some opioid agonists. The compounds which showed the largest rightward shifts in their concentra- tion-response curves, and hence the greatest i/K opioid receptor selectivity, were nalbuphine, [D-Ser2, Leu5]enkephalinyl-Thr6(DSLET), morphine, DAGO and normophine. Responses to tifluadom, Mr 2034, ethylketocyclazocine, butorphanol, nalorphine, proxorphan and U50488 were not inhibited by P-FNA. 4 In the mouse vas deferens, pre-treatment with P-FNA (I x 10-6M) produced a similar shift in the dose-response curves for normophine as in the guinea-pig ileum. The concentration-response curves for the 6-receptor agonists [D-Ala2, D-Leu'] enkephalin (DADLE) and DSLET were, however, also shifted, indicating that P-FNA will also block 6-opioid receptors. 5 Since P-FNA does not block K-opioid receptor-mediated effects, it can be used in the guinea-pig ileum preparation as a selective is-receptor inhibitor. However, its lack of selectivity between JL- and 6- opioid receptors should be taken into account in many other isolated tissues and experiments in vivo. Introduction The alkylating analogue of naltrexone, P-funaltrex- possible to produce a guinea-pig ileum preparation in amine (f-FNA), was first synthesized by Portoghese et vitro that may be devoid of functional ti-opioid al. (1980). In isolated tissue preparations and in vivo, receptors. Furthermore, by measuring the change in P-FNA initially causes a reversible opioid agonist potency of a series of opioid agonists that occurs after effect, but on prolonged contact a selective irreversible P-FNA pretreatment, we have made an estimate of blockade of responses mediated by p-opioid receptors their relative ;./x-receptor selectivity ratio. develops (Ward et al., 1982a,b); the precise site and The mouse vas deferens is a tissue that possesses 6- mechanism ofaction ofP-FNA are uncertain. Ward et opioid receptors in addition to p- and K-opioid al. (1982a) suggested that P-FNA could thus be used to receptors (Lord et al., 1977). Similar experiments in characterize the receptor selectivity of opioid agonists this tissue were carried out to study the effect of P- by measuring the reduction in potency that occurs FNA on 6-receptors. after inhibition of the r-receptor component of their action. The guinea-pig ileum contains opioid receptors only Methods ofthe pt- and K-types (Ward & Takemori, 1976; Lord et al., 1977) and so treatment with P-FNA should leave it Guinea-pig ileum responsive only to K-opioid agonists. We have exten- ded the findings ofWard et al. (1982a) to show that it is The terminal ileum was removed from male Dunkin- ) The Macmillan Press Ltd 1985 900 A.G.HAYES et al. Hartley guinea-pigs (225-275 g), and the 15 cm sec- Laboratories; clonidine hydrochloride, Boehringer tion closest to the caecum discarded. After gently Ingelheim; dihydrocodeine bitartate, Duncan Flock- flushing out the contents, 1.5 cm sections were suspen- hart; ethylketocyclazocine methane sulphonate, Ster- ded in 5 ml organ baths containing a modified Krebs- ling Winthrop; [D-Ala2, N-MePhe4, Met-(0)-ol5]enke- Henseleit solution ofthe following composition (mM): phalin (FK 33824), Sandoz; fentanyl citrate, Janssen; NaCI 118, NaHCO3 29, glucose I 1.1, KCl 4.7, CaCI2 ketocyclazocine, Sterling Winthrop; morphine 2.6, KH2PO4 1.18 and MgSO4 4, gassed with 95% 02 hydrochloride, Macfarlan Smith; Mr 2034 ((- and 5% CO2 and maintained at 37 ± 0.5°C. Each (1 R,5R,9R)-5,9-dimethyl-2-(L-tetrahydrofuryl)-2'- section of ileum was field-stimulated by two coaxial hydroxy-6,7-benzomorphan), Boehringer Ingelheim; ring electrodes using rectangular pulses of 0.5 ms nalbuphine hydrochloride, Endo; nalorphine hy- duration at IV less than maximal voltage at a drobromide, Wellcome; naloxone hydrochloride, frequency of 0.1 Hz. Drugs were added to the bath in Sterling Winthrop; normorphine base, Wellcome; volumes of 10-50 pl. Non-cumulative concentration- pentazocine hydrochloride, Sterling Winthrop; prox- response curves were constructed for an agonist and orphan tartrate, Bristol Laboratories; [D-Ser2, the reference drug, normorphine, and an IC50 concen- Leu5]enkephalinyl-Thr6 (DSLET), Universal tration for 50% inhibition of twitch height was Biologicals; tifluadom hydrochloride, Sandoz; determined. U50488 (trans-3,4-dichloro -N-methyl-N-[2-(1-pyrro- Tissues which were to be pretreated with P-FNA llidinyl)cyclohexyl]benzeneacetamide methane sul- were incubated with it for 30 min. During this time the phonate), Upjohn; Win 42610 (D-4-(cyclopropyl- twitch height was depressed due to the agonist action methyl) - 3,4,5,6 - tetrahydro - 1,5 - methano - 1,4- ben- of f3-FNA. The tissues were then extensively washed zodiazocine-9-amine), Sterling Winthrop. with drug-free bathing medium for at least 60 min until the twitch height recovered and all non-covalent- ly bound P-FNA was removed. Agonist concentra- Results tion-response curves were then re-determined, and dose-ratios were calculated as (IC50 after P-FNA/IC50 As reported by Ward et al. (1982a), P-FNA produced a before P-FNA). reversible inhibition of evoked contractions of the For pA2 determinations, four sections of ileum guinea-pig ileum. The IC50 for this opioid agonist (normal or P-FNA-treated) from the same animal effect was 9 x 10-9M. More prolonged pretreatment were incubated with naloxone for 30 min at a range of of the ileum with ,-FNA (3 x 10-8-3 x 10-6M, concentrations, each preparation being exposed to one 30 min, followed by a 60 min period of frequent concentration only. From the dose-ratio for agonist intermittent washout) produced concentration-depen- before and after 13-FNA treatment, the pA2 was dent parallel rightward shifts of the concentration- calculated according to the method of Arunlakshana response curve for the inhibitory effect ofthe pt-opioid & Schild (1959). The statistical significance of the receptor selective agonist, DAGO, ranging from 4.7 difference between the pA2 values obtained in control fold to 42 fold (Figure 1). The response to the selective and P-FNA-pretreated tissues was determined by use K-receptor agonist, U50488, was unaffected by of Student's t test for unpaired samples. pretreatment of the ileum with concentrations of P- FNA up to I x 10-6M, but concentrations greater Mouse vas deferens than 1 x 10-6M did cause a parallel rightward shift of the dose-response curve (Figure 1). Such tissues took Vasa deferentia were taken from male Glaxo-bred up to 2 h to recover their original twitch height. CRH mice (50-100g) and suspended in Sml organ Control tissues not exposed to P-FNA showed only baths containing modified Krebs-Henseleit solution, shifts of 2 fold or less in the IC50 to either agonist over but lacking magnesium sulphate. Each vas deferens the same period. Pretreatment with P-FNA was stimulated at I V supramaximal voltage with (I X 10-6M or 1 x 10-SM) also failed to shift the trains ofthree 0.5 ms pulses 20 ms apart at a frequency concentration-response curve to the a-adrenoceptor of 0.1 Hz. Concentration-response curves were deter- agonist, clonidine. mined by cumulative dosing, and P-FNA was applied In both control and P-FNA-treated tissues, nalox- as described above for the guinea-pig ileum. one produced parallel shifts ofthe dose-response curve for DAGO. Table I shows the pA2 values for antagon- Sources of drugs ism of DAGO by naloxone in control segments of ileum and those treated with P-FNA (I x 10-6M). In [D-Ala2, D-Leu5]enkephalin (DADLE), Peninsula; [D- control tissues, the pA2 value of 8.58 was within the Ala2, MePhe4, Gly(ol)5]enkephalin (DAGO), Cam- range for antagonism of g-opioid receptors but after bridge Research Biochemicals; bremazocine hydro- treatment of the preparations with 10-6M ,B-FNA, the chloride, Sandoz; butorphanol tartrate, Bristol pA2 fell to 7.78, a value consistent with an action of RECEPTOR SELECTIVITY OF OPIOID AGONISTS 901 However, for the partial agonists DSLET, nalorphine, 40 F proxorphan and butorphanol, which did not usually cause a 50% inhibition of the twitch, the dose-ratios were calculated from parallel sections of the concen- tration-response curves. In the case of morphine and 0 30 - nalbuphine, the concentration-response curves after P- 4- FNA often had significantly shallower slopes than in () untreated tissues. The shift for nalbuphine tended to 0 be smaller in tissues in which the maximum Ua response to 20 - nalbuphine was low. The dose-ratios given in Table 2 CA are for the occasions when parallel shifts were 0 0, obtained. The effects of P-FNA were also investigated in the 10 field-stimulated mouse vas deferens preparation.
Load more

Recommended publications
  • United States Patent (10) Patent No.: US 8,916,581 B2 Boyd Et Al
    USOO891 6581 B2 (12) United States Patent (10) Patent No.: US 8,916,581 B2 Boyd et al. (45) Date of Patent: *Dec. 23, 2014 (54) (S)-N-METHYLNALTREXONE 4,194,045 A 3, 1980 Adelstein 4,203,920 A 5, 1980 Diamond et al. (75) Inventors: Thomas A. Boyd, Grandview, NY (US); 4,241,066 A 12, 1980 Kobylecki et al. H OW d Wagoner,goner, Warwick,s NY (US);s 4,311,833.4,277,605 A T.1/1982 1981 NamikoshiBuyniski et etal. al. Suketu P. Sanghvi, Kendall Park, NJ 4.322,426 A 3/1982 Hermann et al. (US); Christopher Verbicky, 4.326,074 A 4, 1982 Diamond et al. Broadalbin, NY (US); Stephen 4.326,075 A 4, 1982 Diamond et al. “. s 4,377.568 A 3/1983 Chopra et al. Andruski, Clifton Park, NY (US) 4.385,078 A 5/1983 Onda et al. 4.427,676 A 1/1984 White et al. (73) Assignee: Progenics Pharmaceuticals, Inc., 4,430,327 A 2, 1984 Frederickson et al. Tarrytown, NY (US) 4,452,775 A 6/1984 Kent 4,457,907 A 7/1984 Porteret al. (*) Notice: Subject to any disclaimer, the term of this 4,462.839 A 7/1984 McGinley et al. patent is extended or adjusted under 35 4,518.4334,466,968 A 5/19858, 1984 McGinleyBernstein et al. U.S.C. 154(b) by 344 days. 4,533,739 A 8/1985 Pitzele et al. This patent is Subject to a terminal dis- 4,606,9094,556,552 A 12/19858/1986 PorterBechgaard et al.
    [Show full text]
  • Trabajo De Diploma
    Facultad de Química-Farmacia Departamento de Farmacia Trabajo de diploma Título: Evaluación experimental “in vivo” de nuevos compuestos con actividad analgésica seleccionados a través del tamizaje virtual. Autor: Yulier León Mederos Tutores: Dr. Yovani Marrero Ponce MSc. Arelis López Sacerio 2009-2010 Exergo Todos y cada uno de nosotros paga puntualmente su cuota de sacrificio consciente de recibir el premio en la satisfacción del deber cumplido, conscientes de avanzar con todos hacia el Hombre Nuevo que se vislumbra en el horizonte... Che Yulier León Mederos Evaluación experimental “in vivo” de nuevos compuestos con actividad analgésica seleccionados a través del tamizaje virtual Dedicatoria A alguien que se lo merece, por su ayuda y su apoyo durante esta larga carrera como estudiante universitario, mi madre la cual confió siempre en mí y por ver esperado con paciencia esta gran hazaña. Elisa Jorge por verse convertido en mi madre y por su apoyo incondicional cada día que transcurrió en esta escuela. A mis hermanos por estar siempre a mí lado cuando más yo los necesitaba, a mi abuela que no pudo disfrutar esta gran victoria junto a mí, pero allá donde ella está le llegará este lindo regalo. Yulier León Mederos Evaluación experimental “in vivo” de nuevos compuestos con actividad analgésica seleccionados a través del tamizaje virtual Agradecimientos Esta página está dedicada a todas aquellas personas que de un modo u otro hicieron posible la realización de esta tesis. Quisiera agradecer en primer lugar a mi madre que siempre depositó todo su amor y confianza en mí, sobre todo en los momentos difíciles a lo largo de mi carrera A mis hermanos ya que sus consejos siempre fueron buenos y por el aprecio que siento hacia ellos.
    [Show full text]
  • (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]
  • (2) Patent Application Publication (10) Pub. No.: US 2017/0020885 A1 Hsu (43) Pub
    US 20170020885A1 (19) United States (2) Patent Application Publication (10) Pub. No.: US 2017/0020885 A1 Hsu (43) Pub. Date: Jan. 26, 2017 (54) COMPOSITION COMPRISING A (52) U.S. CI. THERAPEUTIC AGENT AND A CPC ......... A61K 31/5377 (2013.01); A61K 9/0053 RESPIRATORY STIMULANT AND (2013.01); A61K 31/485 (2013.01); A61 K METHODS FOR THE USE THEREOF 9/5073 (2013.01); A61K 9/5047 (2013.01): A61K 45/06 (2013.01); A61K 9/0019 (71) Applicant: John Hsu, Rowland Heights, CA (US) (2013.01); A61K 9/209 (2013.01) (72) Inventor: John Hsu, Rowland Heights, CA (US) (57) ABSTRACT (21) Appl. No.: 15/214,421 (22) Filed: Jul. 19, 2016 The present disclosure provides a safe method for anesthesia or the treatment of pain by safely administering an amount Related U.S. Application Data of active agent to a patient while reducing the incidence or severity of suppressed respiration. The present disclosure (60) Provisional application No. 62/195,769, filed on Jul. provides a pharmaceutical composition comprising a thera 22, 2015. peutic agent and a chemoreceptor respiratory stimulant. In one aspect, the compositions oppose effects of respiratory Publication Classification suppressants by combining a chemoreceptor respiratory (51) Int. Cl. stimulant with an opioid receptor agonist or other respira A6 IK 31/5377 (2006.01) tory-depressing drug. The combination of the two chemical A6 IK 9/24 (2006.01) agents, that is, the therapeutic agent and the respiratory A6 IK 9/50 (2006.01) stimulant, may be herein described as the “drugs.” The A6 IK 45/06 (2006.01) present compositions may be used to treat acute and chronic A6 IK 9/00 (2006.01) pain, sleep apnea, and other conditions, leaving only non A6 IK 31/485 (2006.01) lethal side effects.
    [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]
  • 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]
  • United States Patent (10) Patent No.: US 8,003,794 B2 Boyd Et Al
    USO08003794B2 (12) United States Patent (10) Patent No.: US 8,003,794 B2 Boyd et al. (45) Date of Patent: Aug. 23, 2011 (54) (S)-N-METHYLNALTREXONE 4.385,078 A 5/1983 Onda et al. 4.427,676 A 1, 1984 White et al. (75) Inventors: Thomas A. Boyd, Grandview, NY (US); 4,430,327 A 2, 1984 Frederickson et al. 4,452,775 A 6, 1984 Kent Howard Wagoner, Warwick, NY (US); 4,457.907. A 7/1984 Porter et al. Suketu P. Sanghvi, Kendall Park, NJ 4.462,839 A 7/1984 McGinley et al. (US); Christopher Verbicky, 4,466,968 A 8, 1984 Bernstein Broadalbin, NY (US); Stephen t St. A s 3. Miley al. Andruski, Clifton Park, NY (US) 4,556,552- - - A 12/1985 Porter2 et al.a. 4,606,909 A 8/1986 Bechgaard et al. (73) Assignee: Progenics Pharmaceuticals, Inc., 4,615,885 A 10/1986 Nakagame et al. Tarrytown, NY (US) 4,670.287. A 6/1987 Tsuji et al. 4.675, 189 A 6, 1987 Kent et al. (*) Notice: Subject to any disclaimer, the term of this 4,689,332 A 8/1987 McLaughlin et al. patent is extended or adjusted under 35 2.7868 A SE Se U.S.C. 154(b) by 184 days. 4,765,978 A 8/1988 Abidi et al. 4,806,556 A 2/1989 Portoghese (21) Appl. No.: 12/460,507 4,824,853. A 4, 1989 Walls et al. 4,836,212 A 6, 1989 Schmitt et al. (22) Filed: Jul. 20, 2009 4,837.214 A 6, 1989 Tanaka et al.
    [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]
  • 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]
  • (12) Patent Application Publication (10) Pub. No.: US 2002/0010208A1 Shashoua Et Al
    US 2002001 0208A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0010208A1 Shashoua et al. (43) Pub. Date: Jan. 24, 2002 (54) DHA-PHARMACEUTICAL AGENT Related U.S. Application Data CONJUGATES OF TAXANES (63) Continuation of application No. 09/135,291, filed on (76) Inventors: Victor Shashoua, Brookline, MA (US); Aug. 17, 1998, now abandoned, which is a continu Charles Swindell, Merion, PA (US); ation of application No. 08/651,312, filed on May 22, Nigel Webb, Bryn Mawr, PA (US); 1996, now Pat. No. 5,795,909. Matthews Bradley, Layton, PA (US) Publication Classification Correspondence Address: Edward R. Gates, Esq. (51) Int. Cl." ............................................ A61K 31/337 Wolf, Greenfield & Sacks, P.C. (52) U.S. Cl. .............................................................. 514/449 600 Atlantic Avenue Boston, MA 02210 (US) (57) ABSTRACT The invention provides conjugates of cis-docosahexaenoic (21) Appl. No.: 09/846,838 acid and pharmaceutical agents useful in treating noncentral nervous System conditions. Methods for Selectively target 22) Filled: Mayy 1, 2001 ingg pharmaceuticalp agents9. to desired tissues are pprovided. Patent Application Publication Jan. 24, 2002 Sheet 1 of 14 US 2002/0010208A1 1 OO 5 O -5OO - 1 OO-9 -8 -7 -6 -5 -4 LOG-10 OF SAMPLE CONCENTRATION (MOLAR) CCRF-CEM-o- SR ----- RPM-8226----- K-562- - -A - - HL-60 (TB) -g- - MOLT4: ... O Fig. 1 1 OO 5 O -5OO -1 O O -8 -7 -6 -5 -4 -- 9 LOGo OF SAMPLE CONCENTRATION (MOLAR) A549/ATCC-o-NS326. NCEKVX 28. --Q-- NCI-H322M-...-a---Eidsf8::... NC-H522--O-- HOP-62---Fig. 2 a-- NC-H460.-------- Patent Application Publication Jan.
    [Show full text]