DOCSLIB.ORG

Combinations of 5-Ht2a Inverse Agonists And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Combinations of 5-Ht2a Inverse Agonists And (19) TZZ _¥¥¥Z_T (11) EP 2 134 330 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/00 (2006.01) 08.05.2013 Bulletin 2013/19 (86) International application number: (21) Application number: 08744091.3 PCT/US2008/057557 (22) Date of filing: 19.03.2008 (87) International publication number: WO 2008/116024 (25.09.2008 Gazette 2008/39) (54) COMBINATIONS OF 5-HT2A INVERSE AGONISTS AND ANTAGONISTS WITH ANTIPSYCHOTICS KOMBINATIONEN AUS 5-HT2A-INVERSAGONISTEN UND -ANTAGONISTEN MIT ANTIPSYCHOTIKA COMBINAISONS D’AGONISTES INVERSES OU ANTAGONISTES DE 5-HT2A AVEC ANTIPSYCHOTIQUES (84) Designated Contracting States: (74) Representative: Weber, Martin AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Jones Day HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT Prinzregentenstraße 11 RO SE SI SK TR 80538 München (DE) Designated Extension States: AL BA MK RS (56) References cited: WO-A-2004/064738 WO-A-2007/133802 (30) Priority: 19.03.2007 US 895735 P US-A1- 2006 204 486 29.03.2007 US 908921 P 10.12.2007 US 12771 • "ACP-103" DRUGS OF THE FUTURE, PROUS 04.02.2008 US 26092 SCIENCE, ES, vol. 31, no. 11, 1 January 2006 (2006-01-01), pages 939-943, XP002446571 ISSN: (43) Date of publication of application: 0377-8282 23.12.2009 Bulletin 2009/52 • GRAHNEN A E ET AL: "Reduction of haloperidol- induced side effects by ACP-103 in healthy (73) Proprietor: Acadia Pharmaceuticals Inc. volunteers" CLINICAL PHARMACOLOGY & San Diego, CA 92121-1402 (US) THERAPEUTICS, MOSBY-YEAR BOOK, ST LOUIS, MO, US, vol. 77, no. 2, 1 February 2005 (72) Inventors: (2005-02-01), page P98, XP004802689 ISSN: • PETERS, Perry 0009-9236 San Diego, CA 92122 (US) • LI ZHU ET AL: "ACP-103, a 5-HT2A/2C inverse • FURLANO, David agonist, potentiates haloperidol-induced San Diego, CA 92107 (US) dopamine release in rat medial prefrontal cortex • BAHR, Daun and nucleus accumbens" San Diego, CA 92130 (US) PSYCHOPHARMACOLOGY, vol. 183, no. 2, • VAN KAMMEN, Daniel December 2005 (2005-12), pages 144-153, San Diego, CA 92131 (US) XP002497507 ISSN: 0033-3158 • BRANN, Mark • MELTZER ET AL: "Co- therapy with pimavanserin Rye, NH 03870 (US) and risperidone 2 mg provides an improved clinical profile" SCHIZOPHRENIA RESEARCH, ELSEVIER, vol. 98, 16 January 2008 (2008-01-16), page 16, XP022423672 ISSN: 0920-9964 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 2 134 330 B1 Printed by Jouve, 75001 PARIS (FR) EP 2 134 330 B1 Description [0001] The present invention relates to the fields of chemistry and medicine. More particularly, the invention relates to co-administration of 5-HT2A receptor inverse agonists or antagonists with antipsychotics. 5 [0002] Serotonin or 5-hydroxytryptamine (5-HT) plays a significant role in the functioning of the mammalian body. In the central nervous system, 5-HT is an important neurotransmitter and neuromodulator that is implicated in such diverse behaviors and responses as sleeping, eating, locomotion, perceiving pain, learning and memory, sexual behavior, controlling body temperature and blood pressure. In the spinal column, serotonin plays an important role in the control systems of the afferent peripheral nociceptors (Moulignier, Rev. Neurol. 150:3-15, (1994)). Peripheral functions in the 10 cardiovascular, hematological and gastrointestinal systems have also been ascribed to 5-HT. 5-HT has been found to mediate a variety of contractile, secretory, and electrophysiologic effects including vascular and nonvascular smooth muscle contraction, and platelet aggregation. (Fuller, Biology of Serotonergic Transmission, 1982; Bou llin, Serotonin In Mental Abnormalities 1: 316 (1978); Barchas, et al., Serotonin and Behavior, (1973)). The 5- HT2A receptor subtype (also referered to as subclass) is widely yet discretely expressed in the human brain, including many cortical, limbic, and 15 forebrain regions postulated to be involved in the modulation of higher cognitive and affective functions. This receptor subtype is also expressed on mature platelets where it mediates, in part, platelet aggregation, one of the initial steps in the process of vascular thrombosis. [0003] Given the broad distribution of serotonin within the body, it is understandable that tremendous interest in drugs that affect serotonergic systems exists (Gershon, et al., The Peripheral Actions of 5-Hydroxytryptamine, 246 (1989); 20 Saxena, et al., J. Cardiovascular Pharmacol. 15: Supp. 7 (1990)). Serotonin receptors are members of a large human gene family of membrane-spanning proteins that function as transducers of intercellular communication. They exist on the surface of various cell types, including neurons and platelets, where, upon their activation by either their endogenous ligandserotonin orexogenously administered drugs,they change their conformational structure and subsequently interact with downstream mediators of cellular signaling. Many of these receptors, including the 5- HT2A subclass, are G-protein 25 coupled receptors (GPCRs) that signal by activating guanine nucleotide binding proteins (G-proteins), resulting in the generation, or inhibition of, second messenger molecules such as cyclic AMP, inositol phosphates, and diacylglycerol. These second messengers then modulate the function of a variety of intracellular enzymes, including kinases and ion channels, which ultimately affect cellular excitability and function. [0004] At least 15 genetically distinct 5-HT receptor subtypes have been identified and assigned to one of seven 30 families (5-HT1-7). Each subtype displays a unique distribution, preference for various ligands, and functional correlate (s). [0005] Serotonin may be an important component in various types of pathological conditions such as certain psychiatric disorders (depression, aggressiveness, panic attacks, obsessive compulsive disorders, psychosis, schizophrenia, sui- cidal tendency), certain neurodegenerative disorders (Alzheimer-type dementia, Parkinsonism, Huntington’s chorea), anorexia, bulimia, disorders associated with alcoholism, cerebral vascular accidents, and migraine (Meltzer, Neuropsy- 35 chopharmacology, 21:106S-115S (1999); Barnes & Sharp, Neuropharmacology, 38:1083-1152 (1999); Glennon, Neu- rosci. Biobehavioral Rev., 14:35 (1990)). [0006] Given the broad distribution of serotonin within the body and its role in a wide range of physiological and pathological processes, it is understandable that there is tremendous interest in drugs that affect serotonergic sys- tems(Gershon, et al., The Peripheral Actions of 5-Hydroxytryptamine, 246 (1989); Saxena, et al., J. Cardiovascular 40 Pharmacol. 15: Supp. 7 (1990)). [0007] The effects of serotonin are mediated by at least 15 genetically distinct 5-HT receptor subtypes have been identified and assigned to one of seven families (5-HT1-7). Each subtype displays a unique distribution, preference for various ligands, and functional correlate(s). Serotonin receptors are members of a large human gene family of membrane- spanning proteins that function as transducers of intercellular communication. They exist on the surface of various cell 45 types, including neurons and platelets, where, upon their activation by either their endogenous ligand serotonin or exogenously administered drugs, they change their conformational structure and subsequently interact with downstream mediators of cellular signaling. Many of these receptors, including the 5- HT2A subclass, are G- protein coupled receptors (GPCRs)that signal by activating guaninenucleotide binding proteins (G- proteins),resulting in the generation, orinhibition of, second messenger molecules such as cyclic AMP, inositol phosphates, and diacylglycerol. These second messengers 50 then modulate the function of a variety of intracellular enzymes, including kinases and ion channels, which ultimately affect cellular excitability and function. [0008] The 5-HT2A receptor subtype (also referred to as subclass) is widely yet discretely expressed in the human brain, including many cortical, limbic, and forebrain regions postulated to be involved in the modulation of higher cognitive and affective functions. This receptor subtype is also expressed on mature platelets where it mediates, in part, platelet 55 aggregation, one of the initial steps in the process of vascular thrombosis. Recent evidence strongly implicates the 5-HT2 receptor subtype in the etiology of such medical conditions as hypertension, thrombosis, migraine, vasospasm, ischemia, depression, anxiety, psychosis, schizophrenia, sleep disorders and appetite disorders. [0009] Schizophrenia is a particularly devastating neuropsychiatric disorder that affects approximately 1% of the human 2 EP 2 134 330 B1 population. It has been estimated that the total financial cost for the diagnosis, treatment, and lost societal productivity of individuals affected by this disease exceeds 2% of the gross national product (GNP) of the United States. Current treatment primarily involves pharmacotherapy with a class of drugs known as antipsychotics. Antipsychotics are effective in ameliorating positive symptoms (e.g., hallucinations and delusions), yet they frequently do not improve negative 5 symptoms (e.g., social and emotional
Load more

Recommended publications
  • 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, 2020 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, CPTPT: 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]
  • (12) United States Patent (10) Patent No.: US 8.598,119 B2 Mates Et Al
    US008598119B2 (12) United States Patent (10) Patent No.: US 8.598,119 B2 Mates et al. (45) Date of Patent: Dec. 3, 2013 (54) METHODS AND COMPOSITIONS FOR AOIN 43/00 (2006.01) SLEEP DSORDERS AND OTHER AOIN 43/46 (2006.01) DSORDERS AOIN 43/62 (2006.01) AOIN 43/58 (2006.01) (75) Inventors: Sharon Mates, New York, NY (US); AOIN 43/60 (2006.01) Allen Fienberg, New York, NY (US); (52) U.S. Cl. Lawrence Wennogle, New York, NY USPC .......... 514/114: 514/171; 514/217: 514/220; (US) 514/229.5: 514/250 (58) Field of Classification Search (73) Assignee: Intra-Cellular Therapies, Inc. NY (US) None See application file for complete search history. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (56) References Cited U.S.C. 154(b) by 215 days. U.S. PATENT DOCUMENTS (21) Appl. No.: 12/994,560 6,552,017 B1 4/2003 Robichaud et al. 2007/0203120 A1 8, 2007 McDevitt et al. (22) PCT Filed: May 27, 2009 FOREIGN PATENT DOCUMENTS (86). PCT No.: PCT/US2O09/OO3261 S371 (c)(1), WO WOOOf77OO2 * 6, 2000 (2), (4) Date: Nov. 24, 2010 OTHER PUBLICATIONS (87) PCT Pub. No.: WO2009/145900 Rye (Sleep Disorders and Parkinson's Disease, 2000, accessed online http://www.waparkinsons.org/edu research/articles/Sleep PCT Pub. Date: Dec. 3, 2009 Disorders.html), 2 pages.* Alvir et al. Clozapine-Induced Agranulocytosis. The New England (65) Prior Publication Data Journal of Medicine, 1993, vol. 329, No. 3, pp. 162-167.* US 2011/0071080 A1 Mar.
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • A Synthetic Overview of New Molecules with 5-HT1A Binding Affinities
    77 A Synthetic Overview of New Molecules with 5-HT1A Binding Affinities Hernán Pessoa-Mahana* 1 ; Ramiro Araya-Maturana1 , Claudio Saitz, B.1 and C. David Pessoa-Mahana2 1Departamento de Química Orgánica y Fisicoquímica. Facultad de Ciencias Químicas y Farmacéuticas. Universidad de Chile. Olivos 1007.Casilla 233. Santiago 1. Chile 2Departamento de Farmacia. Facultad de Química. Pontificia Universidad Católica de Chile. Vicuña Mackenna 4860-Casilla 306, Correo 22 Santiago-Chile Abstract: The present review discusses the synthetic strategies of new ligands exhibiting mainly 5-HT1A binding affinities. Specifically we focused our attention in the synthesis of compounds structurally related to arylpiperazine, 2-aminotetralin, and benzopyran derivatives. Keywords: serotonin, 5-HT1A ligands, arylpiperazines, aminotetralins, benzopyrans. INTRODUCTION During the last 15 years, seven distinct families of 5-HT receptors have been identified (5-HT1–5-HT7), and at least Depression is one of the most common illnesses, 15 subpopulations have been described for several of these affecting up to one-third of all people at the same time. [4,5]. The 5-HT1A receptors represent a major target for Depressive disorders encompass a variety of conditions neurobiological research and drug developments. A study on including two major forms of unipolar depression (i.e. major distribution of 5-HT1A receptors in the brains of various depression and dysthymia), adjustment disorders, animal species indicates that the highest densities are located subsyndromal depression (minor depression), seasonal in the hippocampus, septum, amygdale, and cortical limbic affective disorder (SAD), premenstrual dysphoric disorder areas. The 5-HT1A receptors located in the raphe nuclei are (PMDD), postpartum depression, atypical depression and known as somatodendritic autoreceptors.
    [Show full text]
  • Chemical Ligand Space of Cereblon Iuliia Boichenko,† Kerstin Bar,̈ Silvia Deiss, Christopher Heim, Reinhard Albrecht, Andrei N
    This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. Article Cite This: ACS Omega 2018, 3, 11163−11171 http://pubs.acs.org/journal/acsodf Chemical Ligand Space of Cereblon Iuliia Boichenko,† Kerstin Bar,̈ Silvia Deiss, Christopher Heim, Reinhard Albrecht, Andrei N. Lupas, Birte Hernandez Alvarez,* and Marcus D. Hartmann* Department of Protein Evolution, Max Planck Institute for Developmental Biology, Max-Planck-Ring 5, 72076 Tübingen, Germany *S Supporting Information ABSTRACT: The protein cereblon serves as a substrate receptor of a ubiquitin ligase complex that can be tuned toward different target proteins by cereblon-binding agents. This approach to targeted protein degradation is exploited in different clinical settings and has sparked the development of a growing number of thalidomide derivatives. Here, we probe the chemical space of cereblon binding beyond such derivatives and work out a simple set of chemical requirements, delineating the metaclass of cereblon effectors. We report co-crystal structures for a diverse set of compounds, including commonly used pharmaceuticals, but also find that already minimalistic cereblon-binding moieties might exert teratogenic effects in zebrafish. Our results may guide the design of a post-thalidomide generation of therapeutic cereblon effectors and provide a framework for the circumvention of unintended cereblon binding by negative design
    [Show full text]
  • Ep 1553091 A1
    Europäisches Patentamt *EP001553091A1* (19) European Patent Office Office européen des brevets (11) EP 1 553 091 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 158(3) EPC (43) Date of publication: (51) Int Cl.7: C07D 263/32, C07D 417/14, 13.07.2005 Bulletin 2005/28 C07D 333/20, C07D 413/12, C07D 417/06 (21) Application number: 04726765.3 (86) International application number: (22) Date of filing: 09.04.2004 PCT/JP2004/005119 (87) International publication number: WO 2004/089918 (21.10.2004 Gazette 2004/43) (84) Designated Contracting States: • SAKAMOTO, Johei AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Takatsuki-shi, Osaka 569-1125 (JP) HU IE IT LI LU MC NL PL PT RO SE SI SK TR • NAKANISHI, Hiroyuki Designated Extension States: Takatsuki-shi, Osaka 569-1125 (JP) AL HR LT LV MK • NAKAGAWA, Yuichi Takatsuki-shi, Osaka 569-1125 (JP) (30) Priority: 09.04.2003 JP 2003105267 • OHTA, Takeshi 03.06.2003 JP 2003157590 Takatsuki-shi, Osaka 569-1125 (JP) • SAKATA, Shohei (71) Applicant: Japan Tobacco Inc. Takatsuki-shi, Osaka 569-1125 (JP) Tokyo 105-8422 (JP) • MORINAGA, Hisayo Takatsuki-shi, Osaka 569-1125 (JP) (72) Inventors: • IKEMOTO, Tomoyuki (74) Representative: Takatsuki-shi, Osaka 569-1125 (JP) von Kreisler, Alek, Dipl.-Chem. et al • TANAKA, Masahiro Deichmannhaus am Dom, Takatsuki-shi, Osaka 569-1125 (JP) Postfach 10 22 41 • YUNO, Takeo 50462 Köln (DE) Takatsuki-shi, Osaka 569-1125 (JP) (54) HETEROAROMATIC PENTACYCLIC COMPOUND AND MEDICINAL USE THEREOF (57) A 5-membered heteroaromatic ring compound represented by the formula [I] 1 2 4 5 7 wherein V is CH or N; W is S or O; R and R are each H etc.; X is -N(R )-, -O-, -S-, -SO2-N(R )-, -CO-N(R )- etc.; L is EP 1 553 091 A1 Printed by Jouve, 75001 PARIS (FR) (Cont.
    [Show full text]
  • Among a Series of Novel D4 Dopamine Receptor Agonists and Antagonists Jeremiah J
    Topographically Based Search for an “Ethogram” Among a Series of Novel D4 Dopamine Receptor Agonists and Antagonists Jeremiah J. Clifford, Ph.D., and John L. Waddington, Ph.D., D.Sc. The effects of three selective D4 antagonists [CP-293,019, 25.0 mg/kg) failed to influence any behavior; whereas, PD L-745,870, and Ro 61-6270] and two putative selective D4 168077 (0.2–25.0 mg/kg) induced nonstereotyped shuffling agonists [CP-226,269 and PD 168077] were compared with locomotion with uncoordinated movements, jerking, and those of the generic D2-like [D2L/S,D3, D4] antagonist yawning, which were insensitive to antagonism by haloperidol to identify any characteristic “ethogram,” in CP-293,019, L-745,870, or haloperidol. These findings fail terms of individual topographies of behavior within the to indicate any “ethogram” for selective manipulation of D4 natural rodent repertoire, as evaluated using ethologically receptor function at the level of the interaction between based approaches. Among the D4 antagonists, neither motoric and psychological processes in sculpting behavioral L-745,870 (0.0016–1.0 mg/kg) nor Ro 61-6270 (0.2–25.0 topography over habituation of exploration through to mg/kg) influenced any behavior; whereas, CP-293,019 quiescence and focus attention on social, cognitive, or other (0.2–25.0 mg/kg) induced episodes of nonstereotyped levels of examination. sniffing, sifting, and vacuous chewing; there were no [Neuropsychopharmacology 22:538–544, 2000] consistent effects on responsivity to the D2-like agonist RU © 2000 American College of Neuropsychopharmacology. 24213. Among the putative D4 agonists, CP-226,269 (0.2– Published by Elsevier Science Inc.
    [Show full text]
  • Pharmaceuticals Appendix
    )&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 ADAPALENE 106685-40-9 ABANOQUIL 90402-40-7 ADAPROLOL 101479-70-3 ABECARNIL 111841-85-1 ADEMETIONINE 17176-17-9 ABLUKAST 96566-25-5 ADENOSINE PHOSPHATE 61-19-8 ABUNIDAZOLE 91017-58-2 ADIBENDAN 100510-33-6 ACADESINE 2627-69-2 ADICILLIN 525-94-0 ACAMPROSATE 77337-76-9 ADIMOLOL 78459-19-5 ACAPRAZINE 55485-20-6 ADINAZOLAM 37115-32-5 ACARBOSE 56180-94-0 ADIPHENINE 64-95-9 ACEBROCHOL 514-50-1 ADIPIODONE 606-17-7 ACEBURIC ACID 26976-72-7 ADITEREN 56066-19-4 ACEBUTOLOL 37517-30-9 ADITOPRIME 56066-63-8 ACECAINIDE 32795-44-1 ADOSOPINE 88124-26-9 ACECARBROMAL 77-66-7 ADOZELESIN 110314-48-2 ACECLIDINE 827-61-2 ADRAFINIL 63547-13-7 ACECLOFENAC 89796-99-6 ADRENALONE 99-45-6 ACEDAPSONE 77-46-3 AFALANINE 2901-75-9 ACEDIASULFONE SODIUM 127-60-6 AFLOQUALONE 56287-74-2 ACEDOBEN 556-08-1 AFUROLOL 65776-67-2 ACEFLURANOL 80595-73-9 AGANODINE 86696-87-9 ACEFURTIAMINE 10072-48-7 AKLOMIDE 3011-89-0 ACEFYLLINE CLOFIBROL 70788-27-1
    [Show full text]
  • Ligand-Based Pharmacophore Studies in the Dopaminergic System Amar P
    University of Wollongong Research Online University of Wollongong Thesis Collection University of Wollongong Thesis Collections 2011 Ligand-based pharmacophore studies in the dopaminergic system Amar P. Inamdar University of Wollongong Recommended Citation Inamdar, Amar P., Ligand-based pharmacophore studies in the dopaminergic system, Doctor of Philosophy thesis, School of Chemistry, University of Wollongong, 2011. http://ro.uow.edu.au/theses/3535 Research Online is the open access institutional repository for the University of Wollongong. For further information contact Manager Repository Services: [email protected]. LIGAND-BASED PHARMACOPHORE STUDIES IN THE DOPAMINERGIC SYSTEM A thesis submitted in partial fulfilment of the requirements for the award of the degree DOCTOR OF PHILOSOPHY From UNIVERSITY OF WOLLONGONG By AMAR P. INAMDAR, B.PHARM., M.PHARM. SCHOOL OF CHEMISTRY November 2011 THESIS CERTIFICATION I, Amar P. Inamdar, declare that this thesis, submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy, in the School of Chemistry, University of Wollongong, is wholly my own work unless otherwise referenced or acknowledged. The document has not been submitted for qualifications at any other academic institution. Amar P. Inamdar November 2011 i ACKNOWLEDGEMENTS I am truly grateful to my supervisor, Prof. John B. Bremner, whose support, encouragement and guidance has helped me immensely in the completion of this project. Most importantly, I am thankful for his patience over all these years and believing in me in spite of various difficult periods in this journey. I know he has sacrificed a significant amount of his personal time to make this happen. I also owe my deepest gratitude to Associate Prof.
    [Show full text]
  • A Phase 3, Multicenter, Randomized, Double-Blind
    Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment NCT Number: NCT03999918 Document Date: 21 Jun 2020 CLINICAL STUDY PROTOCOL UNMASKED PROTOCOL A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment Protocol Number: ACP-103-054 Amendment 4 EudraCT Number: 2018-003251-37 Original Protocol Date: 30 August 2018 Protocol Amendment 1 Date: 05 December 2018 Protocol Amendment 2 Date: 18 March 2019 Protocol Amendment 3 Date: 29 October 2019 Protocol Amendment 4 Date: 21 June 2020 Confidentiality Statement This protocol is the confidential information of ACADIA Pharmaceuticals Inc. and is intended solely for the guidance of the clinical investigation. This protocol may not be disclosed to parties not associated with the clinical investigation or used for any purpose without the prior written consent of ACADIA Pharmaceuticals Inc. Confidential and Proprietary Information of ACADIA Pharmaceuticals Inc. Page 1 of 81 Study: ACP-103-054 Final Version: 1.0 Clinical Study Protocol Amendment 4 UNMASKED VERSION Date: 21 June 2020 SPONSOR SIGNATURE PAGE Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment ACADIA President: President ACADIA Pharmaceuticals Inc. See appended electronic signature page Signature Date ACADIA Study Lead: Executive Director, Clinical Research ACADIA Pharmaceuticals Inc.
    [Show full text]
  • 1 Molecular Biology and Genomic Organization of G Protein–Coupled Serotonin Receptors Wesley K
    THE SEROTONIN RECEPTORS T HE R ECEPTORS KIM A. NEVE, SERIES EDITOR The Serotonin Receptors: From Molecular Pharmacology to Human Therapeutics, EDITED BY Bryan L. Roth, 2006 The Adrenergic Receptors: In the 21st Century, EDITED BY Dianne M. Perez, 2005 The Melanocortin Receptors, EDITED BY Roger D. Cone, 2000 The GABA Receptors, Second Edition, EDITED BY S. J. Enna and Norman G. Bowery, 1997 The Ionotropic Glutamate Receptors, EDITED BY Daniel T. Monaghan and Robert Wenthold, 1997 The Dopamine Receptors, EDITED BY Kim A. Neve and Rachael L. Neve, 1997 The Metabotropic Glutamate Receptors, EDITED BY P. Jeffrey Conn and Jitendra Patel, 1994 The Tachykinin Receptors, EDITED BY Stephen H. Buck, 1994 The Beta-Adrenergic Receptors, EDITED BY John P. Perkins, 1991 Adenosine and Adenosine Receptors, EDITED BY Michael Williams, 1990 The Muscarinic Receptors, EDITED BY Joan Heller Brown, 1989 The Serotonin Receptors, EDITED BY Elaine Sanders-Bush, 1988 The Alpha-2 Adrenergic Receptors, EDITED BY Lee Limbird, 1988 The Opiate Receptors, EDITED BY Gavril W. Pasternak, 1988 The Alpha-1 Adrenergic Receptors, EDITED BY Robert R. Ruffolo, Jr., 1987 The GABA Receptors, EDITED BY S. J. Enna, 1983 The Serotonin Receptors From Molecular Pharmacology to Human Therapeutics Edited by Bryan L. Roth, MD, PhD Department of Biochemistry Case Western Reserve University–School of Medicine Cleveland, OH © 2006 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-8341, E-mail: [email protected]; or visit our Website: http://www.
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]