DOCSLIB.ORG

Ep 2288345 B1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

(19) TZZ ¥_T (11) EP 2 288 345 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/045 (2006.01) A61K 45/06 (2006.01) 10.06.2015 Bulletin 2015/24 A61P 25/00 (2006.01) (21) Application number: 09733496.5 (86) International application number: PCT/IE2009/000021 (22) Date of filing: 20.04.2009 (87) International publication number: WO 2009/128058 (22.10.2009 Gazette 2009/43) (54) PSYCHO-PHARMACEUTICALS PSYCHOPHARMAZEUTIKA PRODUITS PSYCHO-PHARMACEUTIQUES (84) Designated Contracting States: • SCHAFFARZICK R W ET AL: "The anticonvulsant AT BE BG CH CY CZ DE DK EE ES FI FR GB GR activity and toxicity of methylparafynol HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL (dormison) and some other alcohols." SCIENCE PT RO SE SI SK TR (NEW YORK,N.Y.) 12 DEC 1952,vol. 116, no. 3024, 12 December 1952 (1952-12-12), pages 663-665, (30) Priority: 18.04.2008 IE 20080298 XP002538385 ISSN: 0036-8075 • GUPTA B D ET AL: "Emotion as a determinant of (43) Date of publication of application: the effects of drugs and their combination on 02.03.2011 Bulletin 2011/09 different components of behaviour in rats" NEUROPHARMACOLOGY, PERGAMON PRESS, (73) Proprietor: University College Dublin OXFORD, GB, vol. 11, no. 1, 1 January 1972 National University Of Ireland, Dublin (1972-01-01), pages 31-38, XP025490183 ISSN: Dublin 4 (IE) 0028-3908 [retrieved on 1972-01-01] • MAY P R A ET AL: "Dormison, a new type of (72) Inventors: hypnotic: its therapeutic use in psychiatric • REGAN, Ciaran patients" AMERICAN JOURNAL OF Dublin 8 (IE) PSYCHIATRY, AMERICAN PSYCHIATRIC • CONBOY, Lisa ASSOCIATION, WASHINGTON, DC, US, vol. 109, Dublin 18 (IE) no. 12, 1 June 1953 (1953-06-01), pages 881-888, • GANNON, Shane XP009120553 ISSN: 0002-953X Clonbur • KENNEDY D G ET AL: "Methylpentynol (oblivon) County Galway (IE) in the treatment of epilepsy." SCIENCE (NEW YORK, N.Y.) 16 SEP 1955, vol. 122, no. 3168, 16 (74) Representative: MacLachlan & Donaldson September 1955 (1955-09-16), page 515, 2b Clonskeagh Square XP002538386 ISSN: 0036-8075 Clonskeagh Road • MARRIOTT A S ET AL: "Effects of centrally acting Dublin 14 (IE) drugs on exploratory behaviour in rats." BRITISH JOURNAL OF PHARMACOLOGY AND (56) References cited: CHEMOTHERAPY OCT 1965, vol. 25, no. 2, GB-A- 1 415 228 US-A- 4 201 725 October 1965 (1965-10), pages 432-441, US-A- 4 223 041 XP002538476 ISSN: 0366-0826 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 288 345 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 288 345 B1 • GUPTA ET AL: "An examination of the effects of • LEHMANN A ET AL: "A study of the effect of stimulant and depressant drugs on escape/ psychotropic drugs on the processes of avoidance conditioning in strains of rats excitation and inhibition of the CNS by the selectively bred for emotionality/non- audiogenic crisis test in the rat" emotionality: Intertrial activity" 19690501, vol. 8, PSYCHOPHARMACOLOGY, SPRINGER no. 3, 1 May 1969 (1969-05-01), pages 227-234, VERLAG, BERLIN, DE, vol. 3, no. 5, 1 January XP022252590 1962 (1962-01-01), pages 331-343, XP009120399 • GILLHESPY R O: "Methylpentynol carbamate in ISSN: 0033-3158 the management of insomnia and parkinsonism" • MARLEY E ET AL: "Clinical aspects of BRITISH JOURNAL OF CLINICAL PRACTICE,, susceptibility to methylpentynol." JOURNAL OF vol. 12, no. 3, 1 March 1958 (1958-03-01), pages NEUROLOGY, NEUROSURGERY, AND 191-193, XP009120346 ISSN: 0007-0947 PSYCHIATRY MAY 1958, vol. 21, no. 2, May 1958 • HELD R: "Trial therapy with methylpentynol (1958-05), pages 129-140, XP002538387 ISSN: carbamate in ambulatory psychiatric treatment" 0022-3050 SEMAINE DES HOPITAUX DE PARIS, • DICKER S E ET AL: "The effect of methylpentynol EXPANSIONSCIENTIFIQUE FRANCAISE, PARIS, in man." BRITISH JOURNAL OF FR, vol. 32, no. 23, 14 April 1956 (1956-04-14), PHARMACOLOGY AND CHEMOTHERAPY DEC pages 1326-1333, XP009120390 ISSN: 0037-1777 1957, vol. 12, no. 4, December 1957 (1957-12), • BROUSSOLLE P ET AL: "Effects of pages 479-483, XP002538388 ISSN: 0366-0826 methylpentynol carbamate in a severe • J. J Hagan: "Predicting Drug Efficacy for psychosis. Therapeutic action and critical Cognitive Deficits in Schizophrenia", phenomena" JOURNALDE MEDECINE DE LYON, Schizophrenia Bulletin, vol. 31, no. 4, 15 SN, LYON, FR, vol. 41, no. 960, 1 January 1960 September 2005 (2005-09-15), pages 830-853, (1960-01-01), pages 123-127, XP009120391 ISSN: XP055063328, ISSN: 0586-7614, DOI: 1157-0385 10.1093/schbul/sbi058 • HOUSER M ET AL: "Utilization of methylpentynol • Philippe Pichat ET AL: "SSR180711, a Novel carbamate in large doses in psychiatry" Selective [alpha]7 Nicotinic Receptor Partial JOURNAL DE MEDECINE DE LYON,, vol. 38, no. Agonist: (II) Efficacy in Experimental Models 918, 1 January 1958 (1958-01-01), pages 309-317, Predictive of Activity Against Cognitive XP009120547 Symptoms of Schizophrenia", • CIRILLI M ET AL: "On the association of Neuropsychopharmacology, vol. 32, no. 1, 1 psychotonic drugs and C.M.P. (methylparafynol January 2007 (2007-01-01), pages 17-34, carbamate) in psychiatric therapy" ANNALES XP055063326, ISSN: 0893-133X, DOI: MEDICO-PSYCHOLOGIQUES, FORTIN, PARIS, 10.1038/sj.npp.1301188 FR, vol. 119, no. 1, 1 February 1961 (1961-02-01), pages 285-299, XP009120395 ISSN: 0003-4487 • LECOQ R ET AL: "The course of alcoholic desintoxication and its application in some types of serious encephalopathies" ENCEPHALE, PARIS, FR, vol. 53, no. 1, 1 January 1964 (1964-01-01), pages 35-61, XP009120397 ISSN: 0013-7006 2 EP 2 288 345 B1 Description TECHNICAL FIELD 5 [0001] The present invention relates to novel therapeutic uses of Meparfynol and its pharmaceutically acceptable salts. In particular, the present invention concerns the use of Methyl Pentynol (also known as Meparfynol) or a pharma- ceutically acceptable salt thereof for the treatment and/or prevention of schizophrenia. BACKGROUND OF THE INVENTION 10 [0002] Psychosis is a symptom of severe mental illness. Although it is not exclusively linked to any particular psycho- logical or physical state, it is particularly associated with schizophrenia, bipolar disorder (manic depression) and severe clinical depression. Psychosis is characterized by disorders in basic perceptual, cognitive, affective and judgmental processes. Individuals experiencing a psychotic episode may experience hallucinations (often auditory or visual hallu- 15 cinations), hold paranoid or delusional beliefs, experience personality changes and exhibit disorganised thinking (thought disorder). This is sometimes accompanied by features such as a lack of insight into the unusual or bizarre nature of their behaviour, difficulties with social interaction and impairments in carrying out the activities of daily living. [0003] Psychosis is not uncommon in cases of brain injury and may occur after drug use, particularly after drug overdose or chronic use. Certain compounds may be more likely to induce psychosis and some individuals may show 20 greater sensitivity than others. The direct effects of hallucinogenic drugs are not usually classified as psychosis, as long as they abate when the drug is metabolised from the body. Chronic psychological stress is also known to precipitate psychotic states, however the exact mechanism is uncertain. Psychosis triggered by stress in the absence of any other mental illness is known as brief reactive psychosis. Psychosis is thus a descriptive term for a complex group of behaviours and experiences. Individuals with schizophrenia can have long periods without psychosis and those with bipolar disorder, 25 or depression, can have mood symptoms without psychosis. [0004] Hallucinations are defined as sensory perception in the absence of external stimuli. Psychotic hallucinations may occur in any of the five senses and can take on almost any form, which may include simple sensations (such as lights, colours, tastes, smells) to more meaningful experiences such as seeing and interacting with fully formed animals and people, hearing voices and complex tactile sensations. Auditory hallucination, particularly the experience of hearing 30 voices, is a common and often prominent feature of psychosis. Hallucinated voices may talk about, or to the person, and may involve several speakers with distinct personas. Auditory hallucinations tend to be particularly distressing when they are derogatory, commanding or preoccupying. [0005] Psychosis may involve delusional or paranoid beliefs, classified into primary and secondary types. Primary delusions are defined as arising out-of-the-blue and not being comprehensible in terms of normal mental processes, 35 whereas secondary delusions may be understood as being influenced by the person’s background or current situation, that is, represent a delusional interpretation of a "real" situation. Thought disorder describes an underlying disturbance to conscious thought and is classified largely by its effects on the content and form of speech and writing. Affected persons may also show pressure of speech (speaking incessantly and quickly), derailment or flight of ideas (switching topic mid-sentence or inappropriately), thought blocking, rhyming or punning. Psychotic episodes may vary in duration 40 from individuals. In brief, reactive psychosis, the psychotic episode is commonly related directly to a specific stressful life event, so patients spontaneously recover normal functioning, usually within two weeks. In some rare cases, individuals may remain in a state of full blown psychosis for many years, or perhaps have attenuated psychotic symptoms (such as low intensity hallucinations) present at most times. [0006] Psychoses exact a tremendous emotional and economic toll on the patients, their families, and society as a 45 whole.
Recommended publications
  • Seizure Disorders and Commercial Motor Vehicle Driver Safety (Comprehensive Review)

    Seizure Disorders and Commercial Motor Vehicle Driver Safety (Comprehensive Review)

    Evidence Report: Seizure Disorders and Commercial Motor Vehicle Driver Safety (Comprehensive Review) Presented to Federal Motor Carrier Safety Administration November 30, 2007 Prepared for Prepared by MANILA Consulting Group, Inc. ECRI 1420 Beverly Road, Suite 220 5200 Butler Pike McLean, VA 22101 Plymouth Meeting, PA 19462 This report is comprised of research conducted to analyze the impact of Seizure Disorders on Commercial Motor Vehicle Driver Safety. Federal Motor Carrier Safety Administration considers evidence, expert recommendations, and other data, however, all proposed changes to current standards and guidance (guidelines) will be subject to public-notice-and-comment and regulatory processes. FMCSA Evidence Report: Seizure Disorders and Commercial Motor Vehicle Driver Safety 11/30/2007 Policy Statement This evidence report was prepared by ECRI under subcontract to MANILA Consulting Group, Inc., which holds prime Contract No: GS-10F-0177N/DTMC75-06-F-00039 with the Department of Transportation’s Federal Motor Carrier Safety Administration. ECRI is an independent, nonprofit health services research agency and a Collaborating Center for Health Technology Assessment of the World Health Organization. ECRI has been designated an Evidence-based Practice Center (EPC) by the United States Agency for Healthcare Research and Quality. ECRI’s mission is to provide information and technical assistance to the healthcare community worldwide to support safe and cost-effective patient care. The results of ECRI’s research and experience are available through its publications, information systems, databases, technical assistance programs, laboratory services, seminars, and fellowships. The purpose of this evidence report is to provide information regarding the current state of knowledge on this topic.
  • TABLE 1 Studies of Antagonist Activity in Constitutively Active

    TABLE 1 Studies of Antagonist Activity in Constitutively Active

    TABLE 1 Studies of antagonist activity in constitutively active receptors systems shown to demonstrate inverse agonism for at least one ligand Targets are natural Gs and constitutively active mutants (CAM) of GPCRs. Of 380 antagonists, 85% of the ligands demonstrate inverse agonism. Receptor Neutral Antagonist Inverse Agonist Reference Human β2-adrenergic Dichloroisoproterenol, pindolol, labetolol, timolol, Chidiac et al., 1996; Azzi et alprenolol, propranolol, ICI 118,551, cyanopindolol al., 2001 Turkey erythrocyte β-adrenergic Propranolol, pindolol Gotze et al., 1994 Human β2-adrenergic (CAM) Propranolol Betaxolol, ICI 118,551, sotalol, timolol Samama et al., 1994; Stevens and Milligan, 1998 Human/guinea pig β1-adrenergic Atenolol, propranolol Mewes et al., 1993 Human β1-adrenergic Carvedilol CGP20712A, metoprolol, bisoprolol Engelhardt et al., 2001 Rat α2D-adrenergic Rauwolscine, yohimbine, WB 4101, idazoxan, Tian et al., 1994 phentolamine, Human α2A-adrenergic Napthazoline, Rauwolscine, idazoxan, altipamezole, levomedetomidine, Jansson et al., 1998; Pauwels MPV-2088 (–)RX811059, RX 831003 et al., 2002 Human α2C-adrenergic RX821002, yohimbine Cayla et al., 1999 Human α2D-adrenergic Prazosin McCune et al., 2000 Rat α2-adrenoceptor MK912 RX821002 Murrin et al., 2000 Porcine α2A adrenoceptor (CAM- Idazoxan Rauwolscine, yohimbine, RX821002, MK912, Wade et al., 2001 T373K) phentolamine Human α2A-adrenoceptor (CAM) Dexefaroxan, (+)RX811059, (–)RX811059, RS15385, yohimbine, Pauwels et al., 2000 atipamezole fluparoxan, WB 4101 Hamster α1B-adrenergic
  • Inhibitory Effect of Eslicarbazepine Acetate and S-Licarbazepine on 2 Nav1.5 Channels

    Inhibitory Effect of Eslicarbazepine Acetate and S-Licarbazepine on 2 Nav1.5 Channels

    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.24.059188; this version posted August 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Inhibitory effect of eslicarbazepine acetate and S-licarbazepine on 2 Nav1.5 channels 3 Theresa K. Leslie1, Lotte Brückner 1, Sangeeta Chawla1,2, William J. Brackenbury1,2* 4 1Department of Biology, University of York, Heslington, York, YO10 5DD, UK 5 2York Biomedical Research Institute, University of York, Heslington, York, YO10 5DD, UK 6 * Correspondence: Dr William J. Brackenbury, Department of Biology and York Biomedical 7 Research Institute, University of York, Wentworth Way, Heslington, York YO10 5DD, UK. Email: 8 [email protected]. Tel: +44 1904 328284. 9 Keywords: Anticonvulsant, cancer, epilepsy, eslicarbazepine acetate, Nav1.5, S-licarbazepine, 10 voltage-gated Na+ channel. 11 Abstract 12 Eslicarbazepine acetate (ESL) is a dibenzazepine anticonvulsant approved as adjunctive treatment for 13 partial-onset epileptic seizures. Following first pass hydrolysis of ESL, S-licarbazepine (S-Lic) 14 represents around 95 % of circulating active metabolites. S-Lic is the main enantiomer responsible 15 for anticonvulsant activity and this is proposed to be through the blockade of voltage-gated Na+ 16 channels (VGSCs). ESL and S-Lic both have a voltage-dependent inhibitory effect on the Na+ current 17 in N1E-115 neuroblastoma cells expressing neuronal VGSC subtypes including Nav1.1, Nav1.2, 18 Nav1.3, Nav1.6 and Nav1.7.
  • 02/06/2019 12:05 PM Appendix 3745-21-09 Appendix A

    02/06/2019 12:05 PM Appendix 3745-21-09 Appendix A

    ACTION: Final EXISTING DATE: 02/06/2019 12:05 PM Appendix 3745-21-09 Appendix A List of Organic Chemicals for which Paragraphs (DD) and (EE) of Rule 3745-21-09 of the Administrative Code are Applicable Organic Chemical Organic Chemical Acetal Benzaldehyde Acetaldehyde Benzamide Acetaldol Benzene Acetamide Benzenedisulfonic acid Acetanilide Benzenesulfonic acid Acetic acid Benzil Acetic Anhydride Benzilic acid Acetone Benzoic acid Acetone cyanohydrin Benzoin Acetonitrile Benzonitrile Acetophenone Benzophenone Acetyl chloride Benzotrichloride Acetylene Benzoyl chloride Acrolein Benzyl alcohol Acrylamide Benzylamine Acrylic acid Benzyl benzoate Acrylonitrile Benzyl chloride Adipic acid Benzyl dichloride Adiponitrile Biphenyl Alkyl naphthalenes Bisphenol A Allyl alcohol Bromobenzene Allyl chloride Bromonaphthalene Aminobenzoic acid Butadiene Aminoethylethanolamine 1-butene p-aminophenol n-butyl acetate Amyl acetates n-butyl acrylate Amyl alcohols n-butyl alcohol Amyl amine s-butyl alcohol Amyl chloride t-butyl alcohol Amyl mercaptans n-butylamine Amyl phenol s-butylamine Aniline t-butylamine Aniline hydrochloride p-tertbutyl benzoic acid Anisidine 1,3-butylene glycol Anisole n-butyraldehyde Anthranilic acid Butyric acid Anthraquinone Butyric anhydride Butyronitrile Caprolactam APPENDIX p(183930) pa(324943) d: (715700) ra(553210) print date: 02/06/2019 12:05 PM 3745-21-09, Appendix A 2 Carbon disulfide Cyclohexene Carbon tetrabromide Cyclohexylamine Carbon tetrachloride Cyclooctadiene Cellulose acetate Decanol Chloroacetic acid Diacetone alcohol
  • Eslicarbazepine Acetate Longer Procedure No

    Eslicarbazepine Acetate Longer Procedure No

    European Medicines Agency London, 19 February 2009 Doc. Ref.: EMEA/135697/2009 CHMP ASSESSMENT REPORT FOR authorised Exalief International Nonproprietary Name: eslicarbazepine acetate longer Procedure No. EMEA/H/C/000987 no Assessment Report as adopted by the CHMP with all information of a commercially confidential nature deleted. product Medicinal 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: [email protected] http://www.emea.europa.eu TABLE OF CONTENTS 1. BACKGROUND INFORMATION ON THE PROCEDURE........................................... 3 1.1. Submission of the dossier ...................................................................................................... 3 1.2. Steps taken for the assessment of the product..................................................................... 3 2. SCIENTIFIC DISCUSSION................................................................................................. 4 2.1. Introduction............................................................................................................................ 4 2.2. Quality aspects ....................................................................................................................... 5 2.3. Non-clinical aspects................................................................................................................ 8 2.4. Clinical aspects....................................................................................................................
  • Performance Enhancement at the Cost of Potential Brain Plasticity: Neural Ramifications of Nootropic Drugs in the Healthy Developing Brain

    Performance Enhancement at the Cost of Potential Brain Plasticity: Neural Ramifications of Nootropic Drugs in the Healthy Developing Brain

    REVIEW ARTICLE published: 13 May 2014 SYSTEMS NEUROSCIENCE doi: 10.3389/fnsys.2014.00038 Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain Kimberly R. Urban 1 and Wen-Jun Gao 2* 1 Department of Psychology, University of Delaware, Newark, DE, USA 2 Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA Edited by: Cognitive enhancement is perhaps one of the most intriguing and controversial Mikhail Lebedev, Duke University, topics in neuroscience today. Currently, the main classes of drugs used as potential USA cognitive enhancers include psychostimulants (methylphenidate (MPH), amphetamine), Reviewed by: Kimberly Simpson, University of but wakefulness-promoting agents (modafinil) and glutamate activators (ampakine) are Mississippi Medical Center, USA also frequently used. Pharmacologically, substances that enhance the components Christopher R. Madan, University of of the memory/learning circuits—dopamine, glutamate (neuronal excitation), and/or Alberta, Canada norepinephrine—stand to improve brain function in healthy individuals beyond their *Correspondence: baseline functioning. In particular, non-medical use of prescription stimulants such as Wen-Jun Gao, Department of Neurobiology and Anatomy, Drexel MPH and illicit use of psychostimulants for cognitive enhancement have seen a recent University College of Medicine, rise among teens and young adults in schools and college campuses. However, this 2900 Queen Lane, Philadelphia, PA enhancement likely comes with a neuronal, as well as ethical, cost. Altering glutamate 19129, USA function via the use of psychostimulants may impair behavioral flexibility, leading to e-mail: [email protected] the development and/or potentiation of addictive behaviors. Furthermore, dopamine and norepinephrine do not display linear effects; instead, their modulation of cognitive and neuronal function maps on an inverted-U curve.
  • Evidence-Based Guidelines for Treating Depressive Disorders with Antidepressants

    Evidence-Based Guidelines for Treating Depressive Disorders with Antidepressants

    JOP0010.1177/0269881115581093Journal of PsychopharmacologyCleare et al. 581093research-article2015 BAP Guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association Journal of Psychopharmacology 2015, Vol. 29(5) 459 –525 for Psychopharmacology guidelines © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269881115581093 jop.sagepub.com Anthony Cleare1, CM Pariante2 and AH Young3 With expert co-authors (in alphabetical order): IM Anderson4, D Christmas5, PJ Cowen6, C Dickens7, IN Ferrier8, J Geddes9, S Gilbody10, PM Haddad11, C Katona12, G Lewis12, A Malizia13, RH McAllister-Williams14, P Ramchandani15, J Scott16, D Taylor17, R Uher18 and the members of the Consensus Meeting19 Endorsed by the British Association for Psychopharmacology Abstract A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations
  • (19) United States (12) Patent Application Publication (10) Pub

    (19) United States (12) Patent Application Publication (10) Pub

    US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist.
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE

    )&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
  • Euthanasia of Experimental Animals

    Euthanasia of Experimental Animals

    EUTHANASIA OF EXPERIMENTAL ANIMALS • *• • • • • • • *•* EUROPEAN 1COMMISSIO N This document has been prepared for use within the Commission. It does not necessarily represent the Commission's official position. A great deal of additional information on the European Union is available on the Internet. It can be accessed through the Europa server (http://europa.eu.int) Cataloguing data can be found at the end of this publication Luxembourg: Office for Official Publications of the European Communities, 1997 ISBN 92-827-9694-9 © European Communities, 1997 Reproduction is authorized, except for commercial purposes, provided the source is acknowledged Printed in Belgium European Commission EUTHANASIA OF EXPERIMENTAL ANIMALS Document EUTHANASIA OF EXPERIMENTAL ANIMALS Report prepared for the European Commission by Mrs Bryony Close Dr Keith Banister Dr Vera Baumans Dr Eva-Maria Bernoth Dr Niall Bromage Dr John Bunyan Professor Dr Wolff Erhardt Professor Paul Flecknell Dr Neville Gregory Professor Dr Hansjoachim Hackbarth Professor David Morton Mr Clifford Warwick EUTHANASIA OF EXPERIMENTAL ANIMALS CONTENTS Page Preface 1 Acknowledgements 2 1. Introduction 3 1.1 Objectives of euthanasia 3 1.2 Definition of terms 3 1.3 Signs of pain and distress 4 1.4 Recognition and confirmation of death 5 1.5 Personnel and training 5 1.6 Handling and restraint 6 1.7 Equipment 6 1.8 Carcass and waste disposal 6 2. General comments on methods of euthanasia 7 2.1 Acceptable methods of euthanasia 7 2.2 Methods acceptable for unconscious animals 15 2.3 Methods that are not acceptable for euthanasia 16 3. Methods of euthanasia for each species group 21 3.1 Fish 21 3.2 Amphibians 27 3.3 Reptiles 31 3.4 Birds 35 3.5 Rodents 41 3.6 Rabbits 47 3.7 Carnivores - dogs, cats, ferrets 53 3.8 Large mammals - pigs, sheep, goats, cattle, horses 57 3.9 Non-human primates 61 3.10 Other animals not commonly used for experiments 62 4.
  • (12) Patent Application Publication (10) Pub. No.: US 2011/0105536A1 Lewyn-Briscoe Et Al

    (12) Patent Application Publication (10) Pub. No.: US 2011/0105536A1 Lewyn-Briscoe Et Al

    US 2011 01 05536A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0105536A1 Lewyn-Briscoe et al. (43) Pub. Date: May 5, 2011 (54) DOSING REGIMENASSOCATED WITH Publication Classification LONG-ACTING INUECTABLE PALIPERDONE ESTERS (51) Int. Cl. A 6LX 3/59 (2006.01) (76) Inventors: Peter H. Lewyn-Briscoe, A6IP 25/18 (2006.01) Newtown, PA (US); Cristiana Gassmann-Mayer, Pennington, NJ (US); Srihari Gopal, Belle Meade, (52) U.S. Cl. ................................................... S14/259.41 NJ (US); David W. Hough, Wallingford, PA (US); Bart M.M. Remmerie, Gent (BE); Mahesh N. (57) ABSTRACT Samtani, Flemington, NJ (US) The present application provides a method for treating (21) Appl. No.: 12/916,910 patients in need of psychiatric treatment, wherein said patient (22) Filed: Nov. 1, 2010 misses a stabilized dose of a monthly maintenance regimen of paliperidone palmitate. The present application also provides Related U.S. Application Data a method for treating psychiatric patients in need of a Switch (60) Provisional application No. 61/256,696, filed on Oct. ing treatment to paliperidone palmitate in a Sustained release 30, 2009. formulation. Patent Application Publication May 5, 2011 Sheet 1 of 6 US 2011/O105536 A1 FIG. 1 First-Order PrOCeSS Cp V CL Central (2) Zero-Order PrOCeSS Patent Application Publication May 5, 2011 Sheet 2 of 6 US 2011/O105536 A1 FIG. 2 25mgeq 50mgeq m-100mde::::: Missed doSe On WK 4. Patient returns On WK5 Missed doSe On WK 4. Patient returns On WK 6 -8-4 O 4 8 12 16 2024 -8-4 O 4 8 12 1620 24 Missed doSe On WK 4.
  • A Randomized Double-Blind, Double-Dummy

    A Randomized Double-Blind, Double-Dummy

    pISSN 1598-2998, eISSN 2005-9256 Cancer Res Treat. 2014;46(1):19-26 http://dx.doi.org/10.4143/crt.2014.46.1.19 Original Article Open Access A Randomized Double-Blind, Double-Dummy, Multicenter Trial of Azasetron versus Ondansetron to Evaluate Efficacy and Safety in the Prevention of Delayed Nausea and Vomiting Induced by Chemotherapy Hee Yeon Lee, MD 1 Purpose Hoon-Kyo Kim, MD 1 This study was conducted to evaluate the efficacy and safety of azasetron compared Kyung Hee Lee, MD 2 to ondansetron in the prevention of delayed chemotherapy-induced nausea and Bong-Seog Kim, MD 3 vomiting. MD 4 Hong Suk Song, Materials and Methods MD 5 Sung Hyun Yang, This study was a multi-center, prospective, randomized, double-dummy, double-blind MD 6 Joon Hee Kim, and parallel-group trial involving 12 institutions in Korea between May 2005 and MD 7 Yeul Hong Kim, December 2005. A total of 265 patients with moderately and highly emetogenic MD 8 Jong Gwang Kim, chemotherapy were included and randomly assigned to either the azasetron or MD 9 Sang-We Kim, ondansetron group. All patients received azasetron (10 mg intravenously) and MD 10 Dong-Wan Kim, dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every MD 11 Si-Young Kim, 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with MD 12 Hee Sook Park, placebo of ondansetron (orally every 12 hours), and the ondansetron group received Department of Internal Medicine, ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 1St.