DOCSLIB.ORG

WO 2013/067519 A2 10 May 2013 (10.05.2013) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2013/067519 A2 10 May 2013 (10.05.2013) 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 2013/067519 A2 10 May 2013 (10.05.2013) P O P C T (51) International Patent Classification: Not classified 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, IS, JP, KE, KG, KM, KN, KP, PCT/US2012/063585 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 5 November 20 12 (05 .11.20 12) NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (25) Filing Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (26) Publication Language: English ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/555,645 4 November 20 11 (04. 11.201 1) U S kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicant: PURDUE RESEARCH FOUNDATION UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [US/US]; 1281 Win Hentschel Boulevard, West Lafayette, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, IN 47906-4182 (US). EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (72) Inventors: HILL, Catherine, A.; 606 North 5th Street, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Lafayette, IN 47901 (US). WATTS, Val, J.; 35 14 Advent ML, MR, NE, SN, TD, TG). Court, West Lafayette, IN 47906 (US). Published: (74) Agent: BICKLEY, Patrick, M.; Faegre Baker Daniels LLP, 300 North Meridian Street, Suite 2700, Indianapolis, — without international search report and to be republished IN 46204 (US). upon receipt of that report (Rule 48.2(g)) (81) Designated States (unless otherwise indicated, for every — with sequence listingpart of description (Rule 5.2(a)) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (54) Title: INSECT AND TICK G-COUPLED RECEPTORS USEFUL A S TARGETS FOR INSECTICIDES AND COMPOUNDS AND REAGENTS IDENTIFIED USING THE SAME c s- )-Fl nt si¾o!(n= ) Asenapine (n=3) Amp r i e (ti=2) C to rp r a (n=7) < [drug] (M) FIG. 13 © (57) Abstract: An approach to identify and evaluate potential insecticide targets using publicly available genome (DNA) sequence information for arthropod disease vector is provided. The utility of this approach is demonstrated by first determining the molecular o and pharmacological properties of two different dopamine (neurotransmitter) receptors identified in the genome of the yellow fever- and dengue-transmitting mosquito, Aedes aegypti. Next, different chemistries were tested for their ability to interact with one of o these dopamine receptors in a chemical compound screen, and "hit" compounds were identified. Finally, it is shown that some of these chemistries, are selective for the mosquito over the human dopamine receptor and that these chemistries caused significant mortality in mosquito larvae 24 hours after exposure. INSECT AND TICK G-COUPLED RECEPTORS USEFUL AS TARGETS FOR INSECTICIDES AND COMPOUNDS AND REAGENTS IDENTIFIED USING THE SAME PRIORITY CLAIM [0001] This application claims the benefit of United States Provisional Patent Application No. 61/555,645, filed on November 4, 201 1, and incorporated herein by reference in its entirety. STATEMENT OF GOVERNMENTAL RIGHTS [0002] This invention was made with government support under grant contract number 09-CRIS-2-2037/IND01 1474 awarded by the United States Department of Agriculture/National Institute of Food and Agriculture; and grant contract no. prime award W81XWH-10-1-0085, sub-award no. PU201596 awarded by the Department of Defense/Telemedicine and Advanced Technology Research Center. The United States Government has certain rights in the invention. FIELD OF THE INVENTION [0003] Aspects of the invention related to identifying G-coupled receptors in insects such as mosquitoes and the design and use of screens that employ these proteins to identify efficacious insecticides. BACKGROUND [0004] Many neglected tropical infectious diseases affecting humans are transmitted by arthropods such as mosquitoes and ticks. New mode-of-action chemistries are urgently sought to enhance vector management practices in countries where arthropod-borne diseases are endemic, especially where vector populations have acquired widespread resistance to insecticides. SUMMARY [0005] Some aspects of the invention include a method of controlling a population of invertebrates. The method comprises contacting an invertebrate with a compound that includes at least one of the group consisting of asenapine, amperozide, cis-(Z)-flupenthixol, benztropine, methiothepin, loxapine, mianserin, clomipramine, amperozide, butaclamol, clozapine, doxepin, and SCH23390 amitriptyline, chlorpromazine chlorprothixene. In some more particular embodiments, the invertebrate is an insect. In some more particular embodiments, the compound includes at least one of the group consisting of asenapine, amperozide, and cis-(z)-flupenthixol. In some more particular embodiments, the compound includes at least one of the group consisting of benztropine, methiothepin, loxapine, chlorprothixene, mianserin, and clomipramine. In some more particular embodiments, the insect is a mosquito. In some more particular embodiments, the compound includes at least one of the group consisting of asenapine, amperozide, cis-(Z)-flupenthixol, chlorpormazine, amitriptyline, and doxepin. In some more particular embodiments, the insect is a termite. In some more particular embodiments, the compound includes at least one of the group consisting of asenapine, cis-(Z)-flupenthixol, amperozide, amitriptyline, and chlorpromazine. In some more particular embodiments, the insect is a cockroach in some more particular embodiments, the compound includes at least one of the group consisting of amitriptyline, chlorpormazine, cis-(Z)-flupenthixol, asenapine, and amperozide. In some more particular embodiments, the invertebrate is an arthropod. In some more particular embodiments, the invertebrate is a tick. In some more particular embodiments, the compound includes at least one of asenapine, chlorpromazine, and amperozide. [0006] Some aspects of the invention include a method of controlling a population of invertebrates. The method comprises contacting an invertebrate with a compound that includes at least one of the group consisting of amitriptyline hydrochloride, (±)-butaclamol hydrochloride, clozapine, doxepin hydrochloride, cis-(Z)- flupenthixol dihydrochloride, methiothepin maleate, mianserin hydrochloride, niclosamide, piceatannol, and resveratrol. In some more particular embodiments, the invertebrate is any one of an arthropod, an insect, a mosquito, a termite, a cockroach, and a tick. [0007] Some aspects of the invention include a method of controlling a population of invertebrates. The method comprises contacting an invertebrate with a compound that includes at least one of the group of chemical scaffolds consisting of dibenzocycloheptane derivatives, phenothiazine derivatives, thioxanthene derivatives, butyrophenone derivatives, diphenyl amine-containing compounds, quinazoline derivatives, benzodiazoxide derivatives, indole derivatives, piperazinylpyrazolopyrimidines, aryldiaminopryimidine, and hexahydrothienopyridines. In some more particular embodiments, the invertebrate is any one of an arthropod, an insect, a mosquito, a termite, a cockroach, and a tick. [0008] Some aspects of the invention include a method of controlling a population of invertebrates. The method comprises contacting an invertebrate with a compound that includes at least 3 conjugated or non-conjugated rings, wherein said rings are independently selected from the group consisting of aromatic, non-aromatic, heterocyclic and non-heterocyclic rings, and wherein heterocyclic rings may independently includes at least one of the following atoms: C, O, N, or S and wherein each ring may be independently, substituted or unsubstituted with at least one of the following groups or atoms including H, amines, imines, ketones, aldehydes, alcohols, thiols, aromatic rings, alkanes, alkenes, alkynes, halogens and the like. In some more particular embodiments, the invertebrate is any one of an arthropod, an insect, a mosquito, a termite, a cockroach, and a tick. [0009] Some aspects of the invention include a method of controlling a population of insects. The method includes contacting an insect with at least polynucleotide that interferes with the expression of a gene having at least 90 percent homology to SEQ ID. NO. 1 or SEQ ID. NO. 3. In some more particular embodiments, the polynucleotide interferes with the expression of at gene that includes or that hybridizes under stringent conditions to SEQ ID. NO. 1 or SEQ ID. NO. 3. [0010] Some aspects of the invention include a method of screening. The method includes expressing a polynucleotide having at least 90 or 95 percent homology to SEQ ID. NO. 1 or SEQ ID. NO. 3, and contacting cells that express said polynucleotide with at least one exogenous compound, wherein said polynucleotide is not expressed in its native host. In some more particular embodiments, the polynucleotide has at least 90 or 95 percent identity to SEQ ID. NO. 1 or SEQ ID. NO. 3. In some more particular embodiments, the polynucleotide is SEQ ID. NO. 1 or SEQ ID. NO. 3. [0011] Some aspects of the invention include a method of screening. The method includes an isolated polypeptide having at least 90 or 95 percent homology to SEQ ID. NO. 2 or SEQ ID. NO. 4; with at least one exogenous compound and detecting a interaction between said polypeptide and the at least one compound. In some more particular embodiments, the polypeptide has at least 90 or 95 percent identity to SEQ ID. NO. 2 or SEQ ID. NO. 4. In some more particular embodiments, the polypeptide is SEQ ID. NO. 2 or SEQ ID. NO. 4. SEQUENCE LISTING [0012] SEQ ID NO.
Load more

Recommended publications
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 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. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Appendix 13C: Clinical Evidence Study Characteristics Tables
    APPENDIX 13C: CLINICAL EVIDENCE STUDY CHARACTERISTICS TABLES: PHARMACOLOGICAL INTERVENTIONS Abbreviations ............................................................................................................ 3 APPENDIX 13C (I): INCLUDED STUDIES FOR INITIAL TREATMENT WITH ANTIPSYCHOTIC MEDICATION .................................. 4 ARANGO2009 .................................................................................................................................. 4 BERGER2008 .................................................................................................................................... 6 LIEBERMAN2003 ............................................................................................................................ 8 MCEVOY2007 ................................................................................................................................ 10 ROBINSON2006 ............................................................................................................................. 12 SCHOOLER2005 ............................................................................................................................ 14 SIKICH2008 .................................................................................................................................... 16 SWADI2010..................................................................................................................................... 19 VANBRUGGEN2003 ....................................................................................................................
    [Show full text]
  • Characterization of Binding Sites for H-Spiroperidol in Human Retina
    Investigative Ophthalmology & Visual Science, Vol. 29, No. 5, May 1988 Copyright © Association for Research in Vision and Ophthalmology Characterization of Binding Sites For 3H-Spiroperidol in Human Retina Paul McGonigle,* Martin B. Wax,f and Perry B. Molinoff* Binding sites for the D-2-selective antagonist (3H)-spiroperidol were characterized in human retina. Nonspecific binding, measured in the presence of 2 nM (+)-butaclamol, made up 20% of total binding. Scatchard analysis of the binding of (3H)-spiroperidol resulted in linear plots and yielded a Kd value of 87 pM and a Bmax value of 1500 fmol/mg protein. In studies of the inhibition of the binding of (3H)-spiroperidol, (+)-butaclamol was approximately 1000-fold more potent than the (-)-stereo- isomer. The inhibition curve for dopamine was shifted to the right and the Hill coefficient was increased by the addition of 300 ixM GTP. This effect was agonist-specific and suggests that some of the receptors are coupled to stimulation or inhibition of the enzyme adenylate cyclase. The inhibition curves for most of the antagonists had Hill coefficients between 0.6 and 0.8. Hill coefficients were also consistently less than 1.0 for agonists even in the presence of GTP. Nonlinear regression analysis of untransformed data revealed that these shallow inhibition curves were best explained by the presence of two populations of binding sites, 40% of the sites having a high affinity for dopamine in the presence of GTP and domperidone and the remaining 60% having a lower affinity for these ligands. The larger population of sites had a higher affinity for sulpiride, fluphenazine, and N-propylnorapomorphine in the presence of GTP.
    [Show full text]
  • (C) Hit Agreement Between Seeding Densities
    (a) Morphological space (b) Identification of hits (c) Hit agreement between 1500 cells per well 1500 cells per well seeding densities DMSO 8 1.00 Pentamidine 1.00 Wiskostatin Hydroxychloroquine Imatinib 0.75 0.75 4 Gefitinib Compound DMSO Pentamidine 0.50 0.50 0 Vinblastine UMAP2 Wiskostatin Vinblastine 0.25 0.25 Vinblastine −4 Plate at 1500 cells/well Robust Hellinger Distance Wiskostatin Pentamidine 0.00 DMSO 0.00 −4 0 4 0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00 UMAP1 FDR−corrected p−value Plate at 750 cells/well Supp. Figure 1: BioProfiling.jl profiles of plates seeded at 750 and 1500 cells per well curated with are similar. (a) UMAP embedding preserving the cosine distance between the mor-phological profiles aggregated per field of view in the plate seeded with 1500 cells per well. Two out of four dimensions are represented. (b) Robust Hellinger distance and Ro-bust Morphological Perturbation Value (FDR-corrected p-value) of each compound in the plate seeded with 1500 cells per well compared to DMSO. Vertical dotted line indicates an FDR threshold of 0.1 and all compounds on its left are defined as morphological hits. (c) FDR-corrected p-value of the significance of morphological changes induced by each compound in both plates. Dotted lines indicate an FDR threshold of 0.1. CompoundName MOA Targets RMPV750 RMPV1500 (+)-Butaclamol hydrochloride 0.2479179 0 (+)-Cyclazocine 0.0288018 0.0012478 ["ABCC1", "ABCC2", "FPR1", (+/-)-Sulfinpyrazone ["Uricosuric blocker"] "SLC22A12"] 0.0019172 0.015413 (-)-JQ1 0.0003682 0 (-)-Perillic
    [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]
  • US8074644.Pdf
    USOO8074644B2 (12) United States Patent (10) Patent No.: US 8,074,644 B2 Hale et al. (45) Date of Patent: *Dec. 13, 2011 (54) METHOD OF FORMING AN AEROSOL FOR (56) References Cited NHALATION DELVERY (75) Inventors: Ron L. Hale, Sandia Park, NM (US); U.S. PATENT DOCUMENTS Craig C. Hodges, Walnut Creek, CA 1,239,634 A 9, 1917 Stuart (US); Peter M. Lloyd, Walnut Creek, CA (US); Daniel Mufson, Napa, CA (Continued) (US); Daniel D. Rogers, Oakland, CA (US); Soonho Song, Hillsborough, CA FOREIGN PATENT DOCUMENTS (US); Martin J. Wensley, Los Gatos, CA 2152684 1, 1996 CA (US); Daniel J. Myers, Mountain (Continued) View, CA (US); Jeffrey A. McKinney, Lafayette, CA (US); Reynaldo J. OTHER PUBLICATIONS Quintana, Redwood City, CA (US); U.S. Appl. No. 1 1/687,466, filed Mar. 16, 2007, Zaffaroni et al. Joshua D. Rabinowitz, Princeton, NJ (US) (Continued) (73) Assignee: Alexza Pharmaceuticals, Inc., Primary Examiner — Steven Douglas Mountain View, CA (US) (74) Attorney, Agent, or Firm — Swanson & Bratschun, (*) Notice: Subject to any disclaimer, the term of this L.L.C. patent is extended or adjusted under 35 (57) ABSTRACT U.S.C. 154(b) by 272 days. The present invention relates to the inhalation delivery of This patent is Subject to a terminal dis aerosols containing Small particles. Specifically, it relates to a claimer. method of forming an aerosol for use in inhalation therapy. In (21) Appl. No.: 12/471,070 a method aspect of the present invention, a method of forming (22) Filed: May 22, 2009 an aerosol for use in inhalation therapy is provided.
    [Show full text]
  • Binding Assays (Schizophrenia/Haloperidol/Caudate Nucleus/Neuroleptics/Butaclamol) P
    Proc. Nat. Acad. Sci. USA Vol. 72, No. 11, pp. 4376-4380, November 1975 Biochemistry Brain receptors for antipsychotic drugs and dopamine: Direct binding assays (schizophrenia/haloperidol/caudate nucleus/neuroleptics/butaclamol) P. SEEMAN, M. CHAU-WONG, J. TEDESCO, AND K. WONG Department of Pharmacology, University of Toronto, Toronto M5S 1A8, Canada Communicated by Charles H. Best, September 2, 1975 ABSTRACT In order to test the suggestion that antipsy- MATERIALS AND METHODS chotic drugs act by blocking dopamine receptors in the brain, the direct effects of such neuroleptic drugs were tested The majority of the experiments were done on homogenates on the stereospecific binding of [3Hldopamine and of [3H]haloperidol to rat brain striata and their subfractions. or subcellular fractions of rat brain striatum, since this re- The stereospecific component of binding was defined as that gion contains abundant dopamine (24), and presumably amount of [3lH]dopamine or [3Hlhaloperidol bound in the abundant dopamine and neuroleptic receptors. presence of (-)butaclamol (an inactive drug) minus that 1. Preparation of Crude Homogenate of Rat Brain Stri- bound in the presence of (+-butaclamol (a potent neuroleptic atum. Crude homogenates were prepared from rat striata drug); 100 nM butaclamol was used for the [3Hlhaloperidol using male albino Wister rats of between 150 and 250 g. The assay, while 1 MuM butaclamol was used for the [3H1dopamine assay. Various antipsychotic drugs inhibited this stereospe- rats were sacrificed by cervical dislocation, and the brains cific component in both the dopamine and haloperidol as- immediately removed and rinsed in ice-cold 0.9% NaCl. says. These inhibitory potencies correlated with the clinical The striata (each about 30 mg) were dissected out within 5 doses used for controlling schizophrenia.
    [Show full text]
  • Antipsychotics for Treatment of Delirium in Hospitalised Non-ICU Patients
    This is a repository copy of Antipsychotics for treatment of delirium in hospitalised non-ICU patients. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/132847/ Version: Published Version Article: Burry, Lisa, Mehta, S.R., Perreault, M.M et al. (6 more authors) (2018) Antipsychotics for treatment of delirium in hospitalised non-ICU patients. Cochrane Database of Systematic Reviews. CD005594. ISSN 1469-493X https://doi.org/10.1002/14651858.CD005594.pub3 Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Cochrane Database of Systematic Reviews Antipsychotics for treatment of delirium in hospitalised non- ICU patients (Review) Burry L, Mehta S, Perreault MM, Luxenberg JS, Siddiqi N, Hutton B, Fergusson DA, Bell C, Rose L Burry L, Mehta S, Perreault MM, Luxenberg JS, Siddiqi N, Hutton B, Fergusson DA, Bell C, Rose L. Antipsychotics for treatment of delirium in hospitalised non-ICU patients. Cochrane Database of Systematic Reviews 2018, Issue 6.
    [Show full text]
  • Tardive Dyskinesia
    Task Force Reports This is the eighteenth in a series of reports approved by the Board of Trustees of the American Psychiatric Association to give wider dissemination to the findings of APA's many commissions, committees, and task forces that are called upon to evaluate the state of the art in a problem area of current concern to the profession, to related disciplines, and to the public. The findings, opinions, and conclusions of the report do not necessarily represent the views of the officers, trustees, or all members of the Association. Each report, however, does represent the thoughtful judgment and findings of the task force of experts who composed it. These reports are considered a substantive contribution to the ongoing analysis and evaluation of problems, programs, issues, and practices in a given area of concern. Alan A. Stone, M.D. President, APA, 1979-80 Library of Congress Catalogue No. 80-65372 Copyright 1980 by the American Psychiatric Association 1400 K Street, N.W., Washington, D.C. 20005 Printed in U.S.A. 2nd Printing October, 1983 TARDIVE DYSKINESIA Report of the American Psychiatric Association Task Force on Late Neurological Effects of Antipsychotic Drugs Ross J. Baldessarini, M.D., Chairperson Jonathan O. Cole, M.D. John M. Davis, M.D. George Gardos, M.D., Consultant Sheldon H. Preskorn, M.D., Falk Fellow George M. Simpson, M.D. Daniel Tarsy, M.D., Invited Neurologist Approved for Publication by the Council on Research and Development John M. Davis, M.D., Chairperson Charles Gaitz, M.D. Edward Joel Sachar, M.D. George Winokur, M.D.
    [Show full text]
  • Fluphenazine Decanoate (Depot) and Enanthate for Schizophrenia (Review)
    Fluphenazine decanoate (depot) and enanthate for schizophrenia (Review) Maayan N, Quraishi SN, David A, Jayaswal A, Eisenbruch M, Rathbone J, Asher R, Adams CE This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 2 http://www.thecochranelibrary.com Fluphenazine decanoate (depot) and enanthate for schizophrenia (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 6 OBJECTIVES ..................................... 6 METHODS ...................................... 6 RESULTS....................................... 11 Figure1. ..................................... 13 Figure2. ..................................... 16 Figure3. ..................................... 17 ADDITIONALSUMMARYOFFINDINGS . 24 DISCUSSION ..................................... 30 AUTHORS’CONCLUSIONS . 32 ACKNOWLEDGEMENTS . 33 REFERENCES ..................................... 33 CHARACTERISTICSOFSTUDIES . 50 DATAANDANALYSES. 160 Analysis 1.1. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 1 Death. 170 Analysis 1.2. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 2 Global state: 1. Relapse. 171 Analysis 1.3. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 3 Global state: 2. GAS (short term
    [Show full text]
  • Molecular Cloning, Characterization, and Localization of a High
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 8547-8551, September 1993 Pharmacology Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation (rat/Chinese hamster ovary celi/in situ hybridization) MARTIAL RUAT*t, ELISABETH TRAIFFORT*, ROB LEURS*, JOEL TARDIVEL-LACOMBE*, JORGE DIAzt, JEAN-MICHEL ARRANG*, AND JEAN-CHARLES SCHWARTZ* *Unite de Neurobiologic et Pharmacologie (U. 109) de l'Institut National de la Sant6 et de la Recherche Medicale, Centre Paul Broca, 2ter rue d'Alesia, 75014 Paris, France; and tLaboratoire de Physiologie, Faculte de Pharmacie, Universite Rene Descartes, 75006 Paris, France Communicated by James Black, June 7, 1993 (receivedfor review February 1, 1993) ABSTRACT By using a strategy based on nucleotide se- 5-HT2 (16) receptors, which are characterized by a coding quence homology, we have cloned a cDNA encoding a func- sequence interrupted by introns (17, 18) and a positive tional serotonin (5-HI) receptor. The deduced amino acid coupling with phospholipase C. Finally, the not yet cloned sequence ofthe 5--HT7 receptor displays limited homology with 5-HT4 receptor (19) and the recently cloned 5-HT6 receptor that ofother 5-HT receptors. In addition to the seven stretches (20, 21) display submicromolar or micromolar affinity for of hydrophobic amino acids that characterize the superfamily 5-HT and are positively coupled to adenylyl cyclase. of receptors interacting with guanine nudeotide-binding pro- There is evidence, however, for the existence ofadditional teins, the 448-aa sequence of the 5-HT7 receptor contains a 5-HT receptors. For instance, high-affinity [3H]5-HT binding hydrophobic domain located at its N-terminal end.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0076019 A1 Tyers Et Al
    US 20090076019A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0076019 A1 Tyers et al. (43) Pub. Date: Mar. 19, 2009 (54) METHODS FOR TREATING Publication Classification NEUROLOGICAL DISORDERS OR DAMAGE (51) Int. Cl. Inventors: Mike Tyers, Toronto (CA); Phedias A63/496 (2006.01) (75) CI2O 1/02 (2006.01) Diamandis, Toronto (CA); Peter B. A6II 3/445 (2006.01) Dirks, Toronto (CA) A63/64 (2006.01) Correspondence Address: A6IP 25/00 (2006.01) HOWSON AND HOWSON A6IP 25/6 (2006.01) SUITE 210,501 OFFICE CENTER DRIVE A6IP 25/18 (2006.01) FT WASHINGTON, PA 19034 (US) (52) U.S. Cl. ...................... 514/252.13:435/29: 514/317; 514f613 (73) Assignees: Mount Sinai Hospital, Toronto (CA); HSC Research and Development Limited (57) ABSTRACT Partnership, Toronto (CA) A clonogenic neurosphere assay is described that carries out high throughput screens (HTS) to identify potent and/or (21) Appl. No.: 11/871,562 selective modulators of proliferation, differentiation and/or renewal of neural precursor cells, neural progenitor cells and/ (22) Filed: Oct. 12, 2007 or self-renewing and multipotent neural stem cells (NSCs). Compositions comprising the identified modulators and Related U.S. Application Data methods of using the modulators and compositions, in par (60) Provisional application No. 60/851,615, filed on Oct. ticular to treat neurological disorders (e.g. brain or CNS can 13, 2006. cer) or damage are also disclosed. Neurosphere Stein Progenitor Differentiated eEE eEE t Prolifefatic Assay Patent Application Publication Mar. 19, 2009 Sheet 1 of 26 US 2009/0076019 A1 Figure 1 Neurosphere Progenitor O Defeitiated e CE M.
    [Show full text]