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Docteur» at the University François Rabela
UNIVERSITÉ FRANÇOIS – RABELAIS DE TOURS École Doctorale « Santé - Sciences Biologiques - Chimie du Vivant » and UNIVERSITY OF LJUBLJANA, FACULTY OF PHARMACY «Department of Pharmaceutical Chemistry» A cotutelle thesis submitted in fulfillment of the requirements for the degree of «Docteur» at the University François Rabelais of Tours (France) and Doctor of Pharmacy at the University of Ljubljana (Slovenia) In Pharmaceutical Chemistry Publicly defended on the 1st of March 2013 by Mitja KOVAČ in Ljubljana FLUORATION DE DERIVES DU BENZOVESAMICOL POUR L'OBTENTION DE RADIOLIGANDS POTENTIELS DU TRANSPORTEUR VESICULAIRE DE L'ACETYLCHOLINE Under the co-direction of: Associate Professor Sylvie Mavel (MCU, Tours) and Associate Professor Marko Anderluh (Ljubljana) ----------------- JURY for Oral Defense: Ms MAVEL Sylvie – Associate Professor, University François-Rabelais, Tours, France Mr ANDERLUH Marko – Associate Professor, University of Ljubljana, Slovenia Mr DOLLÉ Frédéric – Service Hospitalier Frédéric Joliot, Institut d'Imagerie BioMédicale - CEA, Orsay, France (Reviewer) Mr EMOND Patrick – Professor, University François-Rabelais, Tours, France Ms GMEINER STOPAR Tanja – Assistant Professor, University of Ljubljana, Slovenia (Reviewer) Mr GOBEC Stanislav – Professor, University of Ljubljana, Slovenia (Chairman) This cotutelle PhD was carried out with the collaboration between the University of Tours (Laboratoire de Biophysique Médicale et Pharmaceutique, Unité INSERM U930 - FRANCE) and the University of Ljubljana (Faculty of Pharmacy, Department of Pharmacutical Chemistry - SLOVENIA). The work was supported by a grant from the Slovene Human Resources Development and Scholarship Fund, by a grant from the University of Ljubljana (Inovativna shema za sofinanciranje doktorskega študija za spodbujanje sodelovanja z gospodarstvom in reševanja aktualnih družbenih izzivov - generacija 2010 Univerza v Ljubljani), and by a Slovenia- French bilateral collaboration project (project n° BI-FR/12-13-PROTEUS-007). -
What If a 3 Year Old Takes 12 Flintstone Gummy Vitamins
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(12) United States Patent (10) Patent No.: US 9,687,445 B2 Li (45) Date of Patent: Jun
USOO9687445B2 (12) United States Patent (10) Patent No.: US 9,687,445 B2 Li (45) Date of Patent: Jun. 27, 2017 (54) ORAL FILM CONTAINING OPIATE (56) References Cited ENTERC-RELEASE BEADS U.S. PATENT DOCUMENTS (75) Inventor: Michael Hsin Chwen Li, Warren, NJ 7,871,645 B2 1/2011 Hall et al. (US) 2010/0285.130 A1* 11/2010 Sanghvi ........................ 424/484 2011 0033541 A1 2/2011 Myers et al. 2011/0195989 A1* 8, 2011 Rudnic et al. ................ 514,282 (73) Assignee: LTS Lohmann Therapie-Systeme AG, Andernach (DE) FOREIGN PATENT DOCUMENTS CN 101703,777 A 2, 2001 (*) Notice: Subject to any disclaimer, the term of this DE 10 2006 O27 796 A1 12/2007 patent is extended or adjusted under 35 WO WOOO,32255 A1 6, 2000 U.S.C. 154(b) by 338 days. WO WO O1/378O8 A1 5, 2001 WO WO 2007 144080 A2 12/2007 (21) Appl. No.: 13/445,716 (Continued) OTHER PUBLICATIONS (22) Filed: Apr. 12, 2012 Pharmaceutics, edited by Cui Fude, the fifth edition, People's Medical Publishing House, Feb. 29, 2004, pp. 156-157. (65) Prior Publication Data Primary Examiner — Bethany Barham US 2013/0273.162 A1 Oct. 17, 2013 Assistant Examiner — Barbara Frazier (74) Attorney, Agent, or Firm — ProPat, L.L.C. (51) Int. Cl. (57) ABSTRACT A6 IK 9/00 (2006.01) A control release and abuse-resistant opiate drug delivery A6 IK 47/38 (2006.01) oral wafer or edible oral film dosage to treat pain and A6 IK 47/32 (2006.01) substance abuse is provided. -
Design & Synthesis of Polycyclic Amine Derivatives for Sigma Receptor Activity
UNIVERSITY OF THE WESTERN CAPE Design & Synthesis of Polycyclic Amine derivatives for Sigma Receptor Activity Natasha Strydom February 2013 Supervisor: Prof. S.F. Malan Co-Supervisor: Dr. J. Joubert A thesis submitted in partial fulfilment of the requirements for the degree of Magister Scientiae in the Department of Natural Sciences, University of the Western Cape. KEYWORDS Polycyclic amine Pentacycloundecane Amantadine Heterocyclic amines Sigma receptor Neurodegeneration Drug addiction Blood brain permeability Drug Design Ligand based Structure activity relationship i ABSTRACT New therapeutic strategies are needed for a diverse array of poorly understood neurological impairments. These include neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease, and the psychiatric disorders such as depression, anxiety and drug dependence. Popular neuropharmacotherapies have focused on dopamine (DA), serotonin (5HT), γ-aminobutric acid (GABA) and glutamate systems (Jupp & Lawrence, 2010). However recent research points to the sigma receptor (σR) as a possible neuromodulatory system. Due to its multi-receptor action, the σR can trigger several significant biological pathways. This indicates its ideal potential as a drug target to effectively minimise drug dosage and potential side effects. Currently there are a limited number of σR ligands available and few possess the selectivity to significantly show σR’s role in neurological processes. Polycyclic amines have shown notable sigma activity and provide an advantageous scaffold for drug design that can improve pharmacodynamic and pharmacokinetic properties (Banister et al., 2010; Geldenhuys et al., 2005). Aryl-heterocycle amine groups were also shown to improve σR activity (Piergentili et al., 2009). A series of pentacycloundecane compounds were synthesised which aimed at evaluating the inclusion of a amine containing aryl group in the design compared to previous pentacycloundecane structures containing only two lipophilic regions. -
In Vitro and in Vivo Activity of Cyclopeptide Dmt-C[D-Lys-Phe-Asp]NH2,Amu T Opioid Receptor Agonist Biased Toward Β-Arrestin
Peptides 105 (2018) 51–57 Contents lists available at ScienceDirect Peptides journal homepage: www.elsevier.com/locate/peptides In vitro and in vivo activity of cyclopeptide Dmt-c[D-Lys-Phe-Asp]NH2,amu T opioid receptor agonist biased toward β-arrestin Katarzyna Gach-Janczaka,1, Justyna Piekielna-Ciesielskaa,1, Anna Adamska-Bartłomiejczyka, Karol Wtoreka, Federica Ferrarib, Girolamo Calo’b, Agata Szymaszkiewiczc, ⁎ Joanna Piasecka-Zelgad, Anna Janeckaa, a Department of Biomolecular Chemistry, Medical University, Lodz, Poland b Department of Medical Sciences, Section of Pharmacology and Italian Institute of Neuroscience, University of Ferrara, 44121 Ferrara, Italy c Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Poland d Institute of Occupational Medicine, Research Laboratory for Medicine and Veterinary Products in the GMP Head of Research Laboratory for Medicine and Veterinary Products, Lodz, Poland ARTICLE INFO ABSTRACT Keywords: Morphine and related drugs, which are the most effective analgesics for the relief of severe pain, act through Cyclic opioid peptides activating opioid receptors. The endogenous ligands of these receptors are opioid peptides which cannot be used Binding assay as antinociceptive agents due to their low bioactivity and stability in biological fluids. The major goal of opioid Calcium mobilization assay research is to understand the mechanism of action of opioid receptor agonists in order to improve therapeutic Bioluminescence resonance energy transfer utility of opioids. Analgesic effects of morphine are mediated mostly through activation of the mu opioid re- assay ceptor. However, in the search for safer and more effective drug candidates, analogs with mixed opioid receptor Hot-plate test fi ff Whole gastrointestinal transit test pro le gained a lot of interest. -
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Marrakesh Agreement Establishing the World Trade Organization
No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX -
(12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley Et Al
US 2014O144429A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley et al. (43) Pub. Date: May 29, 2014 (54) METHODS AND DEVICES FOR COMPOUND (60) Provisional application No. 61/887,045, filed on Oct. DELIVERY 4, 2013, provisional application No. 61/831,992, filed on Jun. 6, 2013, provisional application No. 61/794, (71) Applicant: E-NICOTINE TECHNOLOGY, INC., 601, filed on Mar. 15, 2013, provisional application Draper, UT (US) No. 61/730,738, filed on Nov. 28, 2012. (72) Inventors: Martin Wensley, Los Gatos, CA (US); Publication Classification Michael Hufford, Chapel Hill, NC (US); Jeffrey Williams, Draper, UT (51) Int. Cl. (US); Peter Lloyd, Walnut Creek, CA A6M II/04 (2006.01) (US) (52) U.S. Cl. CPC ................................... A6M II/04 (2013.O1 (73) Assignee: E-NICOTINE TECHNOLOGY, INC., ( ) Draper, UT (US) USPC ..................................................... 128/200.14 (21) Appl. No.: 14/168,338 (57) ABSTRACT 1-1. Provided herein are methods, devices, systems, and computer (22) Filed: Jan. 30, 2014 readable medium for delivering one or more compounds to a O O Subject. Also described herein are methods, devices, systems, Related U.S. Application Data and computer readable medium for transitioning a Smoker to (63) Continuation of application No. PCT/US 13/72426, an electronic nicotine delivery device and for Smoking or filed on Nov. 27, 2013. nicotine cessation. Patent Application Publication May 29, 2014 Sheet 1 of 26 US 2014/O144429 A1 FIG. 2A 204 -1 2O6 Patent Application Publication May 29, 2014 Sheet 2 of 26 US 2014/O144429 A1 Area liquid is vaporized Electrical Connection Agent O s 2. -
Visualizza/Apri
UNIVERSITY OF CATANIA FACULTY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL SCIENCES INTERNATIONAL DOCTORATE IN PHARMACEUTICAL SCIENCES XXIII Cycle SEMMELWEIS UNIVERSITY - BUDAPEST FACULTY OF PHARMACY DEPARTMENT OF ORGANIC CHEMISTRY ______________________________________________________ Dr. Antonino Grillo Design and synthesis of new vinca alkaloid derivatives as potential sigma-2 receptor ligands __________________ DOCTORATE THESIS __________________ Coordinator and Supervisor: Prof. Giuseppe Ronsisvalle Co-supervisor: Prof. Péter Mátyus ACADEMIC YEAR 2009-2010 Table of Contents INTRODUCTION 3 SIGMA RECEPTOR SUBCLASSES 5 ANATOMICAL DISTRIBUTION AND RELATED FUNCTIONS 8 NERVOUS SYSTEM 8 PERIPHERAL ORGANS 9 PROPOSED ENDOGENOUS LIGANDS FOR SIGMA RECEPTORS 11 SIGMA-1 RECEPTOR 13 CHARACTERIZATION 13 SUBCELLULAR LOCALIZATION 14 SIGNAL TRANSDUCTION MECHANISM AND MODULATORY ACTION 15 SELECTIVE SIGMA-1 LIGANDS AND PHARMACOPHORIC MODEL 16 SIGMA-2 RECEPTOR 18 CHARACTERIZATION 18 SUBCELLULAR LOCALIZATION 19 SIGMA-2 RECEPTORS AND THE REGULATION OF MOTOR FUNCTION 20 SIGMA-2 RECEPTORS AND CELL DEATH 21 SIGMA-2 LIGANDS AS PROBES FOR IMAGING IN VITRO AND IN VIVO 24 SIGMA-2 LIGANDS 27 PROPOSED PHARMACOPHORIC MODEL FOR SIGMA-2 RECEPTOR 33 IBOGAINE: PHARMACOLOGICAL PROFILE 35 IBOGAINE AND ITS RELATED ALKALOIDS: SAR 37 AIMS OF THE WORK AND DRUG DESIGN 39 INDIVIDUATION OF A NATURAL SCAFFOLD 39 SUPERIMPOSITION STUDY: VINCA-DERIVATIVES UPON IBOGAINE 41 DESIGNED LIGANDS 44 CHEMISTRY 48 RESULTS 53 FINAL REMARKS 54 EXPERIMENTAL SECTION 55 MATERIALS AND METHODS 55 MONOGRAPHIES 56 REFERENCES 79 2 Introduction Sigma receptors were first proposed in the mid-1970s thanks to the studies of Martin and co-workers (1976). They demonstrated that the mania syndrome observed on animal models, after treatment with the bezomorphanic derivative (±)-N-allyl-normetazocine (code number: (±)-SKF 10,047) (Fig. -
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