DOCSLIB.ORG

Wo 2007/039869 A2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Wo 2007/039869 A2 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 12 April 2007 (12.04.2007) WO 2007/039869 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/16 (2006.01) A61P 25/32 (2006.01) kind of national protection available): AE, AG, AL, AM, A61P 25/30 (2006.01) A61P 25/36 (2006.01) AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, (21) International Application Number: GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP, PCT/IB2006/053603 KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LV,LY,MA, MD, MG, MK, MN, MW, MX, MY, MZ, (22) International Filing Date: 3 October 2006 (03.10.2006) NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, (25) Filing Language: Italian TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (30) Priority Data: ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), TO2005A000691 4 October 2005 (04. 10.2005) IT European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LT, LU, LV,MC, NL, PL, PT, (71) Applicant (for all designated States except US): ROT- RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, TAPHARM S.p.A. [IT/IT]; Galleria Unione 5, 1-20122 GN, GQ, GW, ML, MR, NE, SN, TD, TG). Milano (IT). Declarations under Rule 4.17: (72) Inventors; and — as to applicant's entitlement to apply for and be granted a (75) Inventors/Applicants (for US only): MAKOVEC, patent (Rule 4.17(U)) Francesco [IT/IT]; Via Silvio Pellico 14, 1-20050 Lesmo — of inventor ship (Rule 4.17 (iv)) (milano) (IT). CASELLI, Gianfranco [IT/IT]; Via Giu- ditta Sidoli 22, 1-20129 Milano (IT). ROVATI, Lucio Published: Claudio [IT/IT]; Via Ramazzotti 1, 1-20052 Monza (m i — without international search report and to be republished lano) (IT). GIORDANI, Antonio [IT/IT]; Via Cesare upon receipt of that report Angelini 64/d, 1-27100 Pavia (IT). For two-letter codes and other abbreviations, refer to the "G uid (74) Agents: RAMBELLI, Paolo et al.; Corso Emilia 8, ance Notes on Codes and Abbreviations" appearing at the beg in 1-10152 Torino (IT). ning of each regular issue of the PCT Gazette. (54) Title: USE OF NEBOGLAMINE IN THE TREATMENT OF TOXICODEPENDENCY (57) Abstract: Use of neboglamine, (S)-4-amino-N (4, 4-dimethyl-cyclohexyl) glutamic acid (CR 2249) (CAS Registry Number 163000-63-3) , the racemic mixture thereof or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in the treatment of toxicodependency induced by drugs such as CNS sedatives such as opiates, barbiturates, benzodiazepines, alcohol, stimulants such as amphetamines and cocaine, and hallucinogens such as LSD, mescalin, cannabis (marijuana) or fencyclidine. Use of neboglamine in the treatment of toxicodependency The present invention relates to a novel use of (S) -4-amino- N- (4,~4-dimethylcyclohexyl) glutamic acid (CR 2249-neboglamine) (CAS Registry Number 163000-63-3) , the racemic mixture thereof or a pharmaceutically acceptable salt thereof, for use in the treatment of toxicodependency induced by drugs such as Central Nervous System (CNS) sedatives such as opiates, benzodiazepines, barbiturates, alcohol, stimulants such as amphetamines and cocaine, and hallucinogens such as LSD, mescalin, cannabis (marijuana) or fencyclidine. The term "toxicodependency", whether physical or psychological, means the continued and totally implicit use of a drug. Such a use involves the risk of physical damage and the need to stop or limit the consumption of the substance, whether or not the drug taker is in agreement. The term "psychological dependency" means an irresistible impulse (compulsion) to continue self-administering the drug in order to find pleasure. For certain drugs, the psychological dependency is the most important factor in their compulsive use. The term "physical dependency" means a state of habituation to the drug accompanied by tolerance and that is manifested by abstinence syndromes . Tolerance is the need to increase the dose of the drug in order to obtain the same effects as were initially obtained with lower doses; the abstinence syndrome is characterized by painful physical sensations that are manifested when the taking of the drug is stopped. The substances commonly used b y drug takers all induce psychological dependency, while others (the majority) also induce physical dependency. The following groups may b e distinguished: CNS sedatives such a s opiates, benzodiazepines, barbiturates and alcohol, which also all induce physical dependency and tolerance; CNS stimulants, for instance amphetamine and cocaine which induce physical dependency t o a minor extent, if at all; hallucinogens such a s LSD, mescalin, cannabis (marijuana) and fencyclidine. O n the basis o f published preclinical data, the compound neboglamine (CR 224 9 ) has been shown t o have significant modulatory properties on the glycine site (strychnine- insensitive) coupled t o the NMDA receptor complex [Lanza e t a l ., Neuropharmacology 3j5_, 1057-64 (1997)], and also advantageous properties o f promoting memory and learning in various animal models [Garofalo et al. J . Pharm. Pharmacol. 8_, 1290-97 (1996)]. The facilitatory activity exerted b y neboglamine on the NMDA receptor complex should b e o f therapeutic use in conditions o f glutamatergic hypof unctionality . It has been suggested that the NMDA receptor complex may b e involved in a variety o f functional responses t o cocaine, for instance locomotor activity, dependency (continued reinforcement o f self-administration) , tolerance and toxicity (Rockhold R .W., Progress in Drug Research 50j_ 155-92, 1998). It has also recently been demonstrated that glycine i s capable o f inhibiting the locomotor hyperactivity, tolerance and dependency induced b y morphine in mice (K. W . Shin e t a l ., Arch. Pharm. Res. _26 _ 1074-1078, 2003). Thus, neboglamine was evaluated in animal experimental models that may b e considered as predictive for the evaluation of toxicodependency induced by various drugs such as cocaine, morphine and benzodiazepines, which are widely representative of the syndromes caused b y toxicodependency. In the first model used, the inhibitory effect of neboglamine and glycine on the hypermotility induced by cocaine and morphine in rats was evaluated. T-he .motor activity was measured with a video camera and recorded using the Videotrack 512 system as described b y Garofalo (J. Pharm. Pharmacol. 48j_ 1290-1297, 1996). Physiological saline, neboglamine (30 mg/kg) or glycine (300 mg/kg) were administered via the i.p. route 30 minutes before physiological saline, morphine (10 mg/kg s.c.) or cocaine (20 mg/kg s.c). The locomotor activity was recorded for 15 minutes and the total distance covered (in cm) by the animal was recorded b y the computer connected to the video camera. The results thus obtained are collated in Table 1 . Table 1 : Inhibitory activity of neboglamine and glycine on the locomotor hyperactivity induced by cocaine and morphine Glycine (G) 300+F 2900 (-)12.1 - Cocaine (C) F+20 5800 75.7 - Morphine (M) F+10 5300 60.6 - N+C 30+20 3600 9.1 88 .0 ' N+M 30+10 3750 13.6 77 .5 U I G+M 300+10 4250 28.8 52 .5 (1) : The %inhibition i s calculated by the formula: <2) : The % inhibition is calculated by the formula: C + )J Dn -Fπ x m From the data given in Table 1 , it may be seen that both cocaine and morphine show a marked increase in locomotor activity (75.7% and 60.6%, respectively), whereas neboglamine and glycine do not significantly alter the spontaneous motility of the animal. The motor activity accelerated by both •the drugs cocaine and morphine is almost completely antagonized by doses of 30 mg/kg i.p. of neboglamine (88% and 77 .5%, respectively). Glycine also inhibits the morphine-induced hyperkinetic activity, but with a smaller effect (52.5%) and at doses 10 times higher (300 mg/kg as opposed to 30 mg/kg of neboglamine) . In a second experiment, the capacity of neboglamine to inhibit the increased sensitivity (inverse tolerance) induced in rats was evaluated by chronic treatment with morphine. Neboglamine (30 mg/kg) or physiological saline were administered via the i.p. route 30 minutes before morphine (10 mg/kg s.c.) for 6 days. On the seventh day, the test was performed, as described in the preceding experiment, in comparison with a group of animals treated with the same dose of morphine given acutely only on the 7th day (final day of the experiment) . The results thus obtained are collated in Table 2 . Table 2 : Inhibitory activity of neboglamine on the inverse tolerance induced by chronic treatment with morphine in rats The % inhibition is calculated b y the formula: [MC -(MC +N)] Chronic treatment with morphine induces an increase in the motor activity of the rat, compared with the acute effect of the drug, by about 50% (128.6% as opposed to 80.3%). Chronic pre-treatment with neboglamine (30 mg/kg i.p for 7 days) succeeds in almost- completely antagonizing (70.8%) the development of the inverse tolerance induced by the chronic treatment with morphine.
Load more

Recommended publications
  • WO 2011/089216 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 t 28 July 2011 (28.07.2011) WO 2011/089216 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 47/48 (2006.01) C07K 1/13 (2006.01) kind of national protection available): AE, AG, AL, AM, C07K 1/1 07 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) Number: International Application DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/050821 HN, HR, HU, ID, J , IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 2 1 January 201 1 (21 .01 .201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1015 1465. 1 22 January 2010 (22.01 .2010) EP kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, (71) Applicant (for all designated States except US): AS- ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, CENDIS PHARMA AS [DK/DK]; Tuborg Boulevard TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 12, DK-2900 Hellerup (DK).
    [Show full text]
  • Advice Concerning the Addition of Certain Pharmaceutical Products
    U.S. International Trade Commission COMMISSIONERS Daniel R. Pearson, Chairman Shara L. Aranoff, Vice Chairman Jennifer A. Hillman Stephen Koplan Deanna Tanner Okun Charlotte R. Lane Robert A. Rogowsky Director of Operations Karen Laney-Cummings Director of Industries Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Advice Concerning the Addition of Certain Pharmaceutical Products and Chemical Intermediates to the Pharmaceutical Appendix to the Harmonized Tariff Schedule of the United States Investigation No. 332--476 Publication 3883 September 2006 This report was prepared principally by Office of Industries Philip Stone, Project Leader With assistance from Elizabeth R. Nesbitt Primary Reviewers David G. Michels, Office of Tariff Affairs and Trde Agreements, John Benedetto, and Nannette Christ, Office of Economics Administrative Support Brenda F. Carroll Under the direction of Dennis Rapkins, Chief Chemicals and Textiles Division ABSTRACT Under the Pharmaceutical Zero-for-Zero Initiative, which entered into force in 1995, the United States and its major trading partners eliminated tariffs on many pharmaceuticals, their derivatives, and certain chemical intermediates used to make pharmaceuticals. The U.S. list of pharmaceutical products and chemical intermediates eligible for duty-free treatment under the agreement is given in the Pharmaceutical Appendix to the Harmonized Tariff Schedule of the United States. The Pharmaceutical Appendix is periodically updated to provide duty relief for additional such products, including newly developed pharmaceuticals. This report provides advice on the third update to the agreement, in which approximately 1,300 products are proposed to receive duty-free treatment.
    [Show full text]
  • Handbook of Schizophrenia Spectrum Disorders, Volume III
    Handbook of Schizophrenia Spectrum Disorders, Volume III Michael S. Ritsner Editor Handbook of Schizophrenia Spectrum Disorders, Volume III Therapeutic Approaches, Comorbidity, and Outcomes 123 Editor Michael S. Ritsner Technion – Israel Institute of Technology Rappaport Faculty of Medicine Haifa Israel [email protected] ISBN 978-94-007-0833-4 e-ISBN 978-94-007-0834-1 DOI 10.1007/978-94-007-0834-1 Springer Dordrecht Heidelberg London New York Library of Congress Control Number: 2011924745 © Springer Science+Business Media B.V. 2011 No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Foreword Schizophrenia Spectrum Disorders: Insights from Views Across 100 years Schizophrenia spectrum and related disorders such as schizoaffective and mood dis- orders, schizophreniform disorders, brief psychotic disorders, delusional and shared psychotic disorders, and personality (i.e., schizotypal, paranoid, and schizoid per- sonality) disorders are the most debilitating forms of mental illness, worldwide. There are 89,377 citations (including 10,760 reviews) related to “schizophrenia” and 2118 (including 296 reviews) related to “schizophrenia spectrum” in PubMed (accessed on August 12, 2010). The classification of these disorders, in particular, of schizophrenia, schizoaf- fective and mood disorders (referred to as functional psychoses), has been debated for decades, and its validity remains controversial.
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]
  • Novel NMDA Receptor Modulators: an Update Rose M
    Novel NMDA Receptor Modulators: An Update Rose M. Santangelo, Emory University Timothy M. Acker, Emory University Sommer S. Zimmerman, Emory University Brooke M. Katzman, Emory University Katie L. Strong, Emory University Stephen Traynelis, Emory University Dennis C Liotta, Emory University Journal Title: Expert Opinion on Therapeutic Patents Volume: Volume 22, Number 11 Publisher: Taylor &amp; Francis: STM, Behavioural Science and Public Health Titles - No Open Select | 2012-11-01, Pages 1337-1352 Type of Work: Article | Post-print: After Peer Review Publisher DOI: 10.1517/13543776.2012.728587 Permanent URL: https://pid.emory.edu/ark:/25593/s8zwt Final published version: http://dx.doi.org/10.1517/13543776.2012.728587 Copyright information: © 2012 Informa UK Limited Accessed September 25, 2021 7:24 PM EDT NIH Public Access Author Manuscript Expert Opin Ther Pat. Author manuscript; available in PMC 2013 November 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Expert Opin Ther Pat. 2012 November ; 22(11): 1337–1352. doi:10.1517/13543776.2012.728587. Novel NMDA Receptor Modulators: An Update Rose M. Santangelo1, Timothy M. Acker1, Sommer S. Zimmerman1, Brooke M. Katzman1, Katie L. Strong1, Stephen F. Traynelis2, and Dennis C. Liotta‡,1 1Department of Chemistry, Emory University, Atlanta, GA 30322 2Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322 Summary Introduction—The NMDA receptor is a ligand-gated ion channel that plays a critical role in higher level brain processes and has been implicated in a range of neurological and psychiatric conditions. Although initial studies for the use of NMDA receptor antagonists in neuroprotection were unsuccessful, more recently, NMDA receptor antagonists have shown clinical promise in other indications such as Alzheimer’s disease, Parkinson’s disease, pain and depression.
    [Show full text]
  • WO 2009/033054 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 PCT 12 March 2009 (12.03.2009) WO 2009/033054 Al (51) International Patent Classification: (74) Agents: WORRALL, Timothy A. et al.; 370 Seventeenth C07C 309/15 (2006.01) A61K 31/661 (2006.01) Street, Suite 4700, Denver, Colorado 80202 (US). C07F 9/09 (2006.01) A61P 25/00 (2006.01) A61K 31/255 (2006.01) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (21) International Application Number: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, PCT/US2008/075444 CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, (22) International Filing Date: IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, 5 September 2008 (05.09.2008) LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, (25) Filing Language: English RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 60/970,924 7 September 2007 (07.09.2007) US GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, 61/061,059 12 June 2008 (12.06.2008) US ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, (71) Applicant (for all designated States except US): XENO- FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV,MC, MT, NL, PORT, INC.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,737,180 B2 Mak0vec Et Al
    USOO773718OB2 (12) United States Patent (10) Patent No.: US 7,737,180 B2 Mak0Vec et al. (45) Date of Patent: Jun. 15, 2010 (54) USE OF NEBOGLAMINE (CR 2249). ASAN WO WOO3O45913 5, 2003 ANTIPSYCHOTIC AND NEUROPROTECTIVE OTHER PUBLICATIONS Flint et al. A qualitative analysis of the negative symptoms of schizo (75) Inventors: Francesco Makovec, Lesmo (IT); Lucio phrenia interfering with academic and Social Success, and the Claudio Rovati, Monza (IT) exacerbators and diminishers of those symptoms. Dissertation Abstracts International, 2003 vol. 64, No. 12A. p. 4420. Abstract.* (73) Assignee: Rottapharm S.p.A., Milan (IT) Garofalo et al. CR 2249: a New putative memory enhnacer. Behavioural studies on learning and memory in rats and mice. J. (*) Notice: Subject to any disclaimer, the term of this Pharm. Pharmacol. 1996, 48, pp. 1290-1297.* patent is extended or adjusted under 35 Victor Peralta, Are There MoreThanTwo Syndromes in Schizophre U.S.C. 154(b) by 476 days. nia? A Critique of the Positive-Negative Dichotomy, British Journal of Psychiatry (1992), 161, 335-343. (21) Appl. No.: 11/569,545 R.D. Porsolt, Behavioural Despair in Mice: A Primary ScreeningTest for Antidepressants, Arch. int. Pharmacodyn. 229,327-336 (1977). N. R. Swerdlow, Effects of Spiperone, Raclopride, SCH 23390 and (22) PCT Filed: May 23, 2005 Clozapine on Apomorphine Inhibition of Sensorimotor Gating of the Startle Response in the Rat, The Journal of Pharmacology and (86). PCT No.: PCT/EP2005/052340 Experimental Therapeutics, vol. 256, No. 2, U.S. J. David Jentsch. The Neuropsychopharmacology of Phencyclidine: S371 (c)(1), From NMDA Receptor Hypofunction to the Dopamine Hypothesis (2), (4) Date: Nov.
    [Show full text]
  • 06-152 Phrma Newmed Mentill
    201R0eport M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses P R E S E N T E D B Y A M E R I C A ’ S P H A R M A C E U T I C A L R E S E A R C H C O M P A N I E S Pharmaceutical Research Companies Are Developing More Than 300 Medicines to Treat Mental Illnesses merica’s pharmaceutical research and biotech- M E D I C I N E S I N D E V E L O P M E N T F O R M E N T A L nology companies are currently developing 313 I L L N E S S E S * Amedicines to help the nearly 60 million American adults today suffering from some form of mental illness— Addictive Disorders 33 from Alzheimer’s disease to depression and from Anxiety Disorders 38 schizophrenia to addictive disorders, such as dependence Attention-Deficit/ 20 on alcohol or drugs. All of the medicines are either in Hyperactivity Disorder Dementias 90 clinical trials or awaiting review by the Food and Drug Depression 71 Administration. Developmental Disorders 6 Over the past half century, pharmaceutical research has Eating Disorders 33 helped transform mental illnesses from misunderstood Personality Disorders 2 causes of shame and fear into often highly treatable con- ditions. For example, medicines for treating depression are Premenstrual Disorders 2 helping thousands of people suffering from this disease live Schizophrenia 54 productive lives.
    [Show full text]
  • Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs
    Molecules 2016, 21, 75; doi:10.3390/molecules21010075 S1 of S110 Supplementary Materials: Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs Fei Mao 1, Wei Ni 1, Xiang Xu 1, Hui Wang 1, Jing Wang 1, Min Ji 1 and Jian Li * Table S1. Common names, indications, CAS Registry Numbers and molecular formulas of 6891 approved drugs. Common Name Indication CAS Number Oral Molecular Formula Abacavir Antiviral 136470-78-5 Y C14H18N6O Abafungin Antifungal 129639-79-8 C21H22N4OS Abamectin Component B1a Anthelminithic 65195-55-3 C48H72O14 Abamectin Component B1b Anthelminithic 65195-56-4 C47H70O14 Abanoquil Adrenergic 90402-40-7 C22H25N3O4 Abaperidone Antipsychotic 183849-43-6 C25H25FN2O5 Abecarnil Anxiolytic 111841-85-1 Y C24H24N2O4 Abiraterone Antineoplastic 154229-19-3 Y C24H31NO Abitesartan Antihypertensive 137882-98-5 C26H31N5O3 Ablukast Bronchodilator 96566-25-5 C28H34O8 Abunidazole Antifungal 91017-58-2 C15H19N3O4 Acadesine Cardiotonic 2627-69-2 Y C9H14N4O5 Acamprosate Alcohol Deterrant 77337-76-9 Y C5H11NO4S Acaprazine Nootropic 55485-20-6 Y C15H21Cl2N3O Acarbose Antidiabetic 56180-94-0 Y C25H43NO18 Acebrochol Steroid 514-50-1 C29H48Br2O2 Acebutolol Antihypertensive 37517-30-9 Y C18H28N2O4 Acecainide Antiarrhythmic 32795-44-1 Y C15H23N3O2 Acecarbromal Sedative 77-66-7 Y C9H15BrN2O3 Aceclidine Cholinergic 827-61-2 C9H15NO2 Aceclofenac Antiinflammatory 89796-99-6 Y C16H13Cl2NO4 Acedapsone Antibiotic 77-46-3 C16H16N2O4S Acediasulfone Sodium Antibiotic 80-03-5 C14H14N2O4S Acedoben Nootropic 556-08-1 C9H9NO3 Acefluranol Steroid
    [Show full text]
  • Customs Tariff - Schedule
    CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2018 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, UST, following to be employed in commercial fishing or the commercial MT, MUST, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT, PAT, HNT, Artificial bait; KRT, CEUT, UAT: Free Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]
  • Pharmaabkommen A1 E
    Annex I - Pharmaceutical substances, which are free of duty_______________________________________________ Pharmaceutical substances which are Annex I free of duty CAS RN Name 136470-78-5 abacavir 129639-79-8 abafungin 792921-10-9 abagovomab 65195-55-3 abamectin 90402-40-7 abanoquil 183849-43-6 abaperidone 183552-38-7 abarelixe 332348-12-6 abatacept 143653-53-6 abciximab 111841-85-1 abecarnil 167362-48-3 abetimus 154229-19-3 abiraterone 137882-98-5 abitesartan 96566-25-5 ablukast 178535-93-8 abrineurin 91017-58-2 abunidazole 2627-69-2 acadesine 77337-76-9 acamprosate 55485-20-6 acaprazine 56180-94-0 acarbose 514-50-1 acebrochol 26976-72-7 aceburic acid 37517-30-9 acebutolol 32795-44-1 acecainide 77-66-7 acecarbromal 827-61-2 aceclidine 89796-99-6 aceclofenac 77-46-3 acedapsone 127-60-6 acediasulfone sodium 556-08-1 acedoben 80595-73-9 acefluranol 10072-48-7 acefurtiamine 70788-27-1 acefylline clofibrol 18428-63-2 acefylline piperazine 642-83-1 aceglatone 2490-97-3 aceglutamide 110042-95-0 acemannan 53164-05-9 acemetacin 131-48-6 aceneuramic acid 152-72-7 acenocoumarol 807-31-8 aceperone 61-00-7 acepromazine 13461-01-3 aceprometazine 42465-20-3 acequinoline 33665-90-6 acesulfame 118-57-0 acetaminosalol 97-44-9 acetarsol 59-66-5 acetazolamide 3031-48-9 acetergamine 299-89-8 acetiamine 2260-08-4 acetiromate 968-81-0 acetohexamide 546-88-3 acetohydroxamic acid 2751-68-0 acetophenazine 1 / 135 (As of: 1.4.2013) Annex I - Pharmaceutical substances, which are free of duty_______________________________________________ CAS RN Name 25333-77-1 acetorphine
    [Show full text]
  • Customs Tariff - Schedule Xxi - 1
    CUSTOMS TARIFF - SCHEDULE XXI - 1 Section XXI WORKS OF ART, COLLECTORS' PIECES AND ANTIQUES Issued January 1, 2013 CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2013 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, UST, following to be employed in commercial fishing or the commercial MT, MUST, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT: Free Artificial bait; Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]