Selective Knockdown of TASK3 Potassium Channel in Monoamine
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Addictions and the Brain
9/18/2012 Addictions and the Brain TAAP Conference September 14, 2012 Acknowledgements • La Hacienda Treatment Center • American Society of Addiction Medicine • National Institute of Drug Abuse © 2012 La Hacienda Treatment Center. All rights reserved. 1 9/18/2012 Definition • A primary, progressive biochemical, psychosocial, genetically transmitted chronic disease of relapse who’s hallmarks are denial, loss of control and unmanageability. DSM IV Criteria for dependency: At least 3 of the 7 below 1. Withdrawal 2. Tolerance 3. The substance is taken in larger amounts or over a longer period than was intended. 4. There is a persistent desire or unsuccessful efforts to cut down or control substance use. 5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects. 6. Important social, occupational, or recreational activities are given up or reduced because of the substance use. 7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance. © 2012 La Hacienda Treatment Center. All rights reserved. 2 9/18/2012 Dispute between behavior and disease Present understanding of the Hypothalamus location of the disease hypothesis. © 2012 La Hacienda Treatment Center. All rights reserved. 3 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 4 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 5 9/18/2012 Dispute regarding behavior versus disease © 2012 La Hacienda Treatment Center. All rights reserved. 6 9/18/2012 © 2012 La Hacienda Treatment Center. -
Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism -
(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. -
Poisons and Narcotic Drugs (Amendment) Ordinance 1988
AUSTRALIAN CAPITAL TERRITORY Poisons and Narcotic Drugs (Amendment) Ordinance 1988 No. 96 of 1988 I, THE GOVERNOR-GENERAL of the Commonwealth of Australia, acting with the advice of the Federal Executive Council, hereby make the following Ordinance under the Seat of Government (Administration) Act 1910. Dated 15 December 1988 N. M. STEPHEN Governor-General By His Excellency’s Command, CLYDE HOLDING Minister of State for the Arts and Territories An Ordinance to amend the Poisons and Narcotic Drugs Ordinance 1978 Short title 1. This Ordinance may be cited as the Poisons and Narcotic Drugs (Amendment) Ordinance 1988.1 Commencement 2. This Ordinance commences on such date as is fixed by the Minister by notice in the Gazette. Principal Ordinance 3. In this Ordinance, “Principal Ordinance” means the Poisons and Narcotic Drugs Ordinance 1978.2 (Ord. 79/88)—Cat. No. Authorised by the ACT Parliamentary Counsel—also accessible at www.legislation.act.gov.au 2 Poisons and Narcotic Drugs (Amendment) No. 96, 1988 Substances to which Division applies 4. Section 27B of the Principal Ordinance is amended by adding at the end the following paragraphs: “; (f) follicle stimulating hormone; (g) luteinising hormone; (h) thalidomide.”. Grant of authorisation 5. Section 27E of the Principal Ordinance is amended— (a) by omitting from paragraph (1) (a) “or cyclofenil” and substituting “, cyclofenil, follicle stimulating hormone or luteinising hormone”; (b) by omitting from paragraph (1) (b) “and”; and (c) by adding at the end of subsection (1) the following word and paragraph: “; and (d) in the case of an application that relates to thalidomide— the applicant is a specialist physician with no less than 5 years’ experience in the treatment of erythema nodosum leprosum.”. -
Characterization of Mice with Altered Dopamine Transporter and Vesicular Monoamine Transporter 2 Levels
Characterization of Mice with Altered Dopamine Transporter and Vesicular Monoamine Transporter 2 Levels by Shababa Tanzeel Masoud A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Pharmacology and Toxicology University of Toronto © Copyright by Shababa Tanzeel Masoud 2017 Characterization of Mice with Altered Dopamine Transporter and Vesicular Monoamine Transporter 2 Levels Shababa Tanzeel Masoud Doctor of Philosophy Department of Pharmacology and Toxicology University of Toronto 2017 Abstract Dopamine is a key neurotransmitter that regulates motor coordination and dysfunction of the dopamine system gives rise to Parkinson’s disease. Nigrostriatal dopamine neurons are vulnerable to various genetic and environmental insults, suggesting that these cells are inherently at-risk. A cell-specific risk factor for these neurons is the neurotransmitter, dopamine itself. If intracellular dopamine is not appropriately sequestered into vesicles, it can accumulate in the cytosol. Cytosolic dopamine is highly reactive and can trigger oxidative stress, leading to cellular toxicity. Cytosolic dopamine levels are modulated by the plasma membrane dopamine transporter (DAT) that takes up dopamine from the extracellular space, and the vesicular monoamine transporter 2 (VMAT2) that stores dopamine into vesicles. In this thesis, we altered DAT and VMAT2 levels to investigate the detrimental consequences of potentially amplifying cytosolic dopamine in transgenic mice. Project 1 focused on selective over-expression of DAT in dopaminergic cells of transgenic mice (DAT-tg). DAT-tg mice displayed phenotypes of dopaminergic damage: increased dopamine-specific oxidative stress, L-DOPA-reversible fine motor deficits and enhanced sensitivity to toxicant insult, suggesting that increasing DAT- mediated dopamine uptake is detrimental for dopamine cells. -
RTI-4793-14, a New Ligand with High Affinity and Selectivity For
SYNAPSE 16:59-65 (1994) RTI-4793-14, a New Ligand With High Affinity and Selectivity for the ( +)-MK801-Insensitive [3H]1 -[ 1 -( 2- thienyl)cyclohexyl]piperidine Binding Site (PCP Site 2) of Guinea Pig Brain CARL B. GOODMAN, D. NIGEL THOMAS, AGU PERT, BETSEY EMILIEN, JEAN L. CADET, F. IVY CARROLL, BRUCE E. BLOUGH, S. WAYNE MASCARELLA, MICHAEL A. ROGAWSKI, SWAMINATHAN SUBRAMANIAM, AM) RICHARD B. ROTHMAN Clinical Psychopharmacology Section, NIDMNIH Addiction Research Center, Baltimore, Maryland 21224 (C.B.G., B.E., J.L.C., R.B.R.); Biological Psychiatry Branch, NZMH (D.N.T., A.P.) and Neuronal Excitability Section, Epilepsy Research Branch, NINDS (M.A.R., S.S.), NIH, Bethesda, Maryland 20892; and Chemistry and Life Sciences, Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194 (F.I.C., B.E.B., S.W.M.) KEY WORDS Phencyclidine receptor, RTI-4793-14, PCP, Biogenic amine reuptake carrier, ( + )-MK801, Guinea pig brain ABSTRACT L3HlTCP, an analog of the dissociative anesthetic phencyclidine (PCP), binds with high affinity to two sites in guinea pig brain membranes, one that is MK-801 sensitive and one that is not. The MK-801-sensitive site (PCP site 1) is associated with NMDA receptors, whereas the MK-801-insensitive site (PCP site 2) may be associated with biogenic amine transporters (BAT).Although several “BAT ligands” are known that bind selectively to PCP site 2 and not to PCP site 1 (such as indatraline), these corn- pounds have low affinity for site 2 (K, values > 1 pM). Here we demonstrate that the novel pyrrole RTI-4793-14 is a selective, high affinity ligand for PCP site 2. -
)&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 -
Lega Italiana Per La Lotta Contro La Malattia Di Parkinson Le Sindromi Extrapiramidali E Le Demenze
LIMPE lega italiana per la lotta contro la malattia di parkinson le sindromi extrapiramidali e le demenze Web site: http://www.parkinson-limpe.it/ XXIX National Congress Lecce 23–25 October 2002 Parkinson Parkinsonism Dementia: from Biotechnology to Medical Management SELECTED SHORT PAPERS Scientific Committee Bruno Bergamasco, Giovanni U. Corsini, Mario Manfredi, Stefano Ruggieri, Pierfranco Spano Secretariat LIMPE Viale dell’Università 30, 00185 Roma Tel. and Fax: +39-06-4455618 E-mail: [email protected] Neurol Sci (2003) 24:149–150 DOI 10.1007/s10072-003-0103-5 123I-Ioflupane/SPECT binding to to the dopamine transporter (DAT) may be better suited and provide more-accurate estimation of degeneration. Several striatal dopamine transporter (DAT) tracers that bind to DAT and utilize SPECT are available; uptake in patients with Parkinson’s they are all cocaine derivatives. The most widely used are disease, multiple system atrophy, and [123I]β-CIT and 123I-Ioflupane ([123I]FP-CIT) [3, 4]. The main advantage of 123I-Ioflupane is that a steady state allow- progressive supranuclear palsy ing SPECT imaging is reached 3 h after a single bolus injec- 1 2 1 tion of the radioligand, compared with the 18–24 h required A. Antonini (౧) • R. Benti • R. De Notaris 1 1 1 for [123I]β-CIT. Therefore DAT imaging with 123I-Ioflupane S. Tesei • A. Zecchinelli • G. Sacilotto 1 1 1 1 can be completed the same day. N. Meucci • M. Canesi • C. Mariani • G. Pezzoli 123 P. Gerundini2 Several studies have demonstrated the usefulness of I- 1 Centro per la malattia di Parkinson, Dipartimento di Ioflupane SPECT imaging in the diagnosis of parkinsonism. -
Pdf; Chi 2015 DPP Air in Cars.Pdf; Dodson 2014 DPP Dust CA.Pdf; Kasper-Sonnenberg 2014 Phth Metabolites.Pdf; EU Cosmetics Regs 2009.Pdf
Bouge, Cathy (ECY) From: Nancy Uding <[email protected]> Sent: Friday, January 13, 2017 10:24 AM To: Steward, Kara (ECY) Cc: Erika Schreder Subject: Comments re. 2016 CSPA Rule Update - DPP Attachments: DPP 131-18-0 exposure.pdf; Chi 2015 DPP air in cars.pdf; Dodson 2014 DPP dust CA.pdf; Kasper-Sonnenberg 2014 phth metabolites.pdf; EU Cosmetics Regs 2009.pdf Please accept these comments from Toxic-Free Future concerning the exposure potential of DPP for consideration during the 2016 CSPA Rule update. Regards, Nancy Uding -- Nancy Uding Grants & Research Specialist Toxic-Free Future 206-632-1545 ext.123 http://toxicfreefuture.org 1 JES-00888; No of Pages 9 JOURNAL OF ENVIRONMENTAL SCIENCES XX (2016) XXX– XXX Available online at www.sciencedirect.com ScienceDirect www.elsevier.com/locate/jes Determination of 15 phthalate esters in air by gas-phase and particle-phase simultaneous sampling Chenchen Chi1, Meng Xia1, Chen Zhou1, Xueqing Wang1,2, Mili Weng1,3, Xueyou Shen1,4,⁎ 1. College of Environmental & Resource Sciences, Zhejiang University, Hangzhou 310058, China 2. Zhejiang National Radiation Environmental Technology Co., Ltd., Hangzhou 310011, China 3. School of Environmental and Resource Sciences, Zhejiang Agriculture and Forestry University, Hangzhou 310058, China 4. Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, China ARTICLE INFO ABSTRACT Article history: Based on previous research, the sampling and analysis methods for phthalate esters (PAEs) Received 24 December 2015 were improved by increasing the sampling flow of indoor air from 1 to 4 L/min, shortening the Revised 14 January 2016 sampling duration from 8 to 2 hr. -
Compositions and Methods for Selective Delivery of Oligonucleotide Molecules to Specific Neuron Types
(19) TZZ ¥Z_T (11) EP 2 380 595 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 26.10.2011 Bulletin 2011/43 A61K 47/48 (2006.01) C12N 15/11 (2006.01) A61P 25/00 (2006.01) A61K 49/00 (2006.01) (2006.01) (21) Application number: 10382087.4 A61K 51/00 (22) Date of filing: 19.04.2010 (84) Designated Contracting States: • Alvarado Urbina, Gabriel AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Nepean Ontario K2G 4Z1 (CA) HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL • Bortolozzi Biassoni, Analia Alejandra PT RO SE SI SK SM TR E-08036, Barcelona (ES) Designated Extension States: • Artigas Perez, Francesc AL BA ME RS E-08036, Barcelona (ES) • Vila Bover, Miquel (71) Applicant: Nlife Therapeutics S.L. 15006 La Coruna (ES) E-08035, Barcelona (ES) (72) Inventors: (74) Representative: ABG Patentes, S.L. • Montefeltro, Andrés Pablo Avenida de Burgos 16D E-08014, Barcelon (ES) Edificio Euromor 28036 Madrid (ES) (54) Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types (57) The invention provides a conjugate comprising nucleuc acid toi cell of interests and thus, for the treat- (i) a nucleic acid which is complementary to a target nu- ment of diseases which require a down-regulation of the cleic acid sequence and which expression prevents or protein encoded by the target nucleic acid as well as for reduces expression of the target nucleic acid and (ii) a the delivery of contrast agents to the cells for diagnostic selectivity agent which is capable of binding with high purposes. -
(12) United States Patent (10) Patent No.: US 7,893,053 B2 Seed Et Al
US0078.93053B2 (12) United States Patent (10) Patent No.: US 7,893,053 B2 Seed et al. (45) Date of Patent: Feb. 22, 2011 (54) TREATING PSYCHOLOGICAL CONDITIONS WO WO 2006/127418 11, 2006 USING MUSCARINIC RECEPTORM ANTAGONSTS (75) Inventors: Brian Seed, Boston, MA (US); Jordan OTHER PUBLICATIONS Mechanic, Sunnyvale, CA (US) Chau et al. (Nucleus accumbens muscarinic receptors in the control of behavioral depression : Antidepressant-like effects of local M1 (73) Assignee: Theracos, Inc., Sunnyvale, CA (US) antagonist in the porSolt Swim test Neuroscience vol. 104, No. 3, pp. 791-798, 2001).* (*) Notice: Subject to any disclaimer, the term of this Lind et al. (Muscarinic acetylcholine receptor antagonists inhibit patent is extended or adjusted under 35 chick Scleral chondrocytes Investigative Ophthalmology & Visual U.S.C. 154(b) by 726 days. Science, vol.39, 2217-2231.* Chau D., et al., “Nucleus Accumbens Muscarinic Receptors in the (21) Appl. No.: 11/763,145 Control of Behavioral Depression: Antidepressant-like Effects of Local M1 Antagonists in the Porsolt Swin Test.” Neuroscience, vol. (22) Filed: Jun. 14, 2007 104, No. 3, Jun. 14, 2001, pp. 791-798. Bechtel, W.D., et al., “Biochemical pharmacology of pirenzepine. (65) Prior Publication Data Similarities with tricyclic antidepressants in antimuscarinic effects only.” Arzneimittelforschung, vol. 36(5), pp. 793-796 (May 1986). US 2007/O293480 A1 Dec. 20, 2007 Chau, D.T. et al., “Nucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local Related U.S. Application Data Mantagonist in the Porsolt Swim test.” Neuroscience, vol. 104(3), (60) Provisional application No. -
Ep 0790250 A2
Patentamt Europaisches || || 1 1| || || || 1 1| || 1 1|| 1 1 1| (19) J European Patent Office Office europeen des brevets (11) EP 0 790 250 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication:ation: (51) |nt. ci.6: C07D 471/08, A61 K 31/435 20.08.1997 Bulletin 1997/34 (21) Application number: 97107218.6 (22) Date of filing: 11.08.1994 (84) Designated Contracting States: • RESEARCH TRIANGLE INSTITUTE AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL Research Triangle Park, NC 27709-21 94 (US) PTSE (72) Inventor: (30) Priority: 12.08.1993 US 105747 The designation of the inventor has not yet bee 28.02.1 994 US 203222 n filed (62) Document number(s) of the earlier application(s) in (74) Representative: VOSSI US & PARTNER accordance with Art. 76 EPC: Siebertstrasse 4 94925860.2 / 0 71 3 484 81 675 Munchen (DE) (71) Applicants: Remarks: This application was filed on 30 - 04 - 1 997 as a THE GOVERNMENT OF THE UNITED STATES O divisional application to the application mentioned F AMERICA, as represented by THE SECRETAR under INID code 62. Y, DEPARTMENT OF HEALTH AND HUMAN SER VICES Rockville, MD 20852 (US) (54) Inhibitors of biogenic amine transporters (57) The present invention provides a compound having the following structure CM The present invention also provides a pharmaceutical composition comprising the compound above and a pharma- ^ ceutically acceptable carrier. The present invention further provides a method for treating a disease characterized by a q dopamine deficiency which comprises administering to a subject in need of such treatment an amount of the pharma- lO ceutical composition above effective to treat the disease.