DOCSLIB.ORG

Notice of Entitlement

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Notice of Entitlement i PZOO/OOl : Section 29 AUSTRALIA Patents Act 1990 NOTICE OF ENTITLEMENT We Jenapharm GmbH of Otto-Schott-Strasse 15, 07745 Jena, Germany, the Applicant in respect of Application No. 29741/95 state the following: ft• · · · ft0 1. Jenapharm GmbH is the Nominated Person in respect of the application. • · · 0 • ••ftft 2, The actual inventors of the invention, the subject of the application, are Sifgrid ft• · » ft ft β · SCHWARZ, Walter ELGER, Hans-Joachim SIEMANN, Gudrun REDDERSEN ft ft 3 ft · ft and Birgitt SCHNEIDER • • ft ftft • ft 9 ft ft • • <ί·ft 3 The Nominated Person is entitled to the grant of a patent in respect of the application because the said Nominated Person derived title to the invention from ft ft ft the actual inventors by virtue of assignment contract. • ft · eftft ft • ft··ft * • ft ft ftft 4 The Nominated Person is entitled to claim priority from the application listed in the • ft ft ft ftft ft declaration under Article 8 of the PCT because the Nominated Person is the ft ft ftft applicant in respect of the application listed in the declaration under Article 8 of the ft ft PCT, and because the application was the first application made in a Convention country in respect of the invention. ft » ft ftftft ft ft ft ft ·ft _ ________________ ._____________________________ 7 October, 1998 A member of the firm of DAVIES COLLISON CAVE for and on behalf of the applicant h i •o, -jpcwjnsxp.s .7/10)58, IjlKMM1 AU9529741 (12) PATENT ABRIDGMENT (11) Document No. AU-B-29741/95 (19) AUSTRALIAN PATENT OFFICE (10) Acceptance No. 699701 (54) Title ESTRA-1,3,5(10)-TRIENE DERIVATIVES, METHODS OF PREPARING SUCHCOMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM International Patent Classification(s) (51)6 CO7J 041/00 A61K 031/56 C07J 043/00 C07J 053/00 (21) Application No.: 29741/95 (22) Application Date : 03.07.95 (87) PCT Publication Number: WO96/05216 (30) Priority Data (31) Number (32) Date (33) Country 4429397 09.08.94 DE GERMANY (43) Publication Date : 07.03.96 (44) Publication Date of Accepted Application : 10.12.98 (71) Applicant(s) JENAPHARM GMBH (72) Inventor(s) HANS-JOACHIM SIEMANN; SIGFRID SCHWARZ; WALTER ELGER; GUDRUN REDDERSEN; BIRGITT SCHNEIDER (74) Attorney or Agent DAVIES COLLISON CAVE , GPO Box 3876, SYDNEY NSW 2001 (57) Claim 1. Estra-l,3,5(lO)-trien derivatives of the general Formula I II O wherein R is a RT^N group, withR1 and R2, independently of each other, represent a hydrogen atom, a CrC5-alkyl residue or, together with the N atom, a polymethylenimino residue with 4 to 6 C atoms or a morpholine residue, R3 is a hydrogen atom or an alkyl group with 1-5 C atoms, R4 is a hydrogen atom, a hydroxy group, an esterified hydroxy group, a haloalkyl group with 1-5 C atoms or an alkoxy group with 1-5 C atoms, era· (11) AU-B-29741/95 -2- (10)699701 R3 and R6 are a hydrogen atom each or, together, stand for a methylene group, R7, R8 and R9, independently of each other, stand for a hydrogen atom or a hydroxy group, and ring B may contain one or two double bonds or R8 is an alkinyl residue with up to 5 carbon atoms with the proviso that R1 and R2 are hydrogen atoms, or at least one of the residues R3, R4, R3, Rfi or R7 is not hydrogen and R1 and R3 have a different meaning from each other , or R8 and R9 together may represent an oxygen atom with the proviso that at least one of the residues R3, R4, R3, R6 or R7 is different from hydrogen, or R3 and R8 may represent a vinylene or ethylene group. 4, Pharmaceutical compositions containing an estra-1,3,5(10)-trien derivative according to Claim 1 or 2 which may be combined with pharmaceutically safe adjuvants and carriers. OPI DATE 07/03/96 APPLN. ID 29741/95 AOJP DATE 26/04/96 PCT NUMBER PCT/DE95/00877 AU9529741 (51) Internationale Patentklassifikation 6 ; (11) Internationale VeroiTentlichungsnununer: WO 96/05216 C07J 41/00, A61K 31/56, C07J 53/00, Al (43) Internationales 43/00 Veroffentlichungsdatum: 22. Februar 1996 (22.02.96) (74) Anwalt: WABLAT, Wolfgang; Potsdamer Chaussee 48, D- (21) Internationales Aktenzeichen: PCT/DE95/00877 14129 Berlin (DE). (22) Internationales Anmeldedatum: 3. Juli 1995 (03.07.95) (81) Bestimmungsstaaten: AU, BG, BR, BY, CA, CN, CZ, FI, HU, (30) Prioritatsdaten: JP, KP, KR, KZ, LK, LV, MN, NO. NZ. PL, RO, RU, SK, P 44 29 397.6 9. August 1994 (09.08.94) DE UA, US, UZ, VN, europfiisches Patent (AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE). (71) Anmelder (fiir alle Bestimmungsstaaten ausser US): JE- NAPHARM GMBH [DE/DE]; Otto-Schott-Strasse 15, VerSfTentlicht D-07745 Jena (DE). Mit internationalem Recherchenbericht. (71) Anmelder (nur fiir US): SIEMANN, Christei (Erbin des verstoibenen Erfinders) [DE/DE]; Fritz-Ritter-Strasse 6, D- 07747 Jena (DE). (72) Erflnder: SIEMANN, Hans-Joachim (verstorben). I 8 (72) Erfinder; und (75) Erflnder/Anmelder (nur fiir US): SCHWARZ, Sigfrid [DE/DE]; Ottogerd-Mtihlmann-Strasse 17, D-07743 Jena 1 (DE). ELGER, Walter [DE/DE]; SchorlemeraUee 12b, D-14195 Berlin (DE). REDDERSEN, Gudrun [DE/DE]; HUgelstrasse 25, D-07749 Jena (DE). SCHNEIDER, Birgitt , [DE/DE]; Damaschkeweg 19, D-07745 Jena (DE). (54) Title: ESTRA-1,3,5(10)-TRIENE DERIVATIVES, METHODS OF PREPARING SUCH COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM (54) Bezeichnung: ESTRA-1,3,5( 10)-TRIEN-DERIVATE, VERFAHREN ZU IHRER HERSTELLUNG UND DIESE VERBINDUNGEN ‘ ENTHALTENDE PHARMAZEUT1SCHE ZUSAMMENSETZUNGEN (57) Abstract The invention concerns novel estra-1,3,5(10)-triene amidosulphamates with an R-SO2-O- group in the 3-position, R being an R*R2N- group in which R* and R2, independently of each other, are a hydrogen atom, an alkyl group with 1 to 5 C-atoms or, together with the N-atom, a polymethyleneimino group with 4 to 6 C-atoms or a motpholino group. The compounds described are suitable for use in hormonal contraception and in climacteric hormone-replacement therapy (HRT), as well as in the treatment of gynaecological and andrological conditions. The compounds described thus only have a low hepatic oestrogenicity, Also described are methods of preparing the compounds described, plus the preparation of pharmaceutical compositions containing them. (57) Zusammenfaaeung Die Erfindung betrifft neue Estra-1,3,5(10)-trien-Amidosulfamate, welche an der 3-Position eine R-SCh-O-Gruppe tragen, wobei R cine R'R2N-Gnippe 1st, worin R* und R2 unabhingig voneinander ein Wasserstoffatora, einen Alkylrest mit 1-5 C-Atomen oder zusammen mit dem N-Atom einen Polymethylenimlnorest mit 4 bis 6 C-Atomen oder einen Morpholinorcst bedeuten. Die erfindungsgemaflen Verbindungen sind zur hormonalen Kontrazeption und in der klimakterischen Hormon-Replacement-Therapie (HRT) sowie zur Behandlung gyndkologischer und andrologischer Krankheitsbilder geeignet. Daher weisen die erfindungsgemaflen Verbindungen nur eine geringe hepatische Estrogenitat auf. Femer werdcn Verfahren zur Hentellung der erfindungsgemaflen Verbindungen beschrieben, sowie zur Herstellung pharmazeutischer ’ Zusammensetzungen. j ' 1 totifmnn I 1 Estra-1, 3, 5(10)-Trien Derivatives, Processes for their Preparation and Pharmaceutical Compositions containing these Compounds I Description This invention relates to new estra-1, 3, 5(10)-trien sulfamates. I 10 Estrogens play a major role in hormonal contraception and climacteric hormone replacement therapy (HRT) as well as in the treatment of gynecological (e.g. £ I mammary carcinoma) and andrological (e.g. prostate carcinoma) diseases. Ϊ; In HRT and for contraception, estrogens are predominantly used in combination 15 with a gestagen, e.g, levonorgestrel, desogestrel, gestodene, drospirorenone, norethisterone, cyproterone acetate, chlormadinone acetate and dienogest. For contraception, estrogens are required for reliable suppression of follicular maturation and ovulation. They will also substitute for widely suppressed 20 endogenic, ovarian secretion of estradiol. Such substitution is essential to maintenance of an artificial menstruation cycle and other functions of sexual organs, which would not be satisfactorily achievable by a gestagen alone. Endogenic estrogens also have important central nervous and metabolic functions I 25 in the female organism. Normal estrogen levels make a crucial contribution to individual comfort and wellbeing (L. Zichella; Clinical Management of the Menopausal Woman; Int. J. of Fertil. and Menop. Studies, 38, Suppl. 1 [1993], 15-22). Their presence, 3 0 through various mechanisms, may help in preventing development of cardiovascular diseases, for example, by generating "favourable" lipoprotein patterns in the blood (G. Samsioe; Hormone Replacement Therapy and Cardiovascular Disease; Int. J. of Fertil. and Menop. Studies, 38, Suppl. 1 [1993], 0 23-29), inhibition of lipid incorporation into vascular walls (T.B. Clarkson; 35 Experimental Effects of Progesterone versus Progestins on Arterial Wall; Gynecol, Endocrinol., 6: Suppl. 1 [1992], 15), reduction of blood pressure through JI4il-20.DOC ί \ , gwwtsiwwj »ws#?e? ? O f 2 5 ; favourable action on vascular tonus (R.A. Lobo; Estrogen and Cardiovascular i Disease; Ann, New York Acad. Sciences, 592 [1990], 286-294), reduction of j perfusion resistance in important vascular regions, attenuation of contractile stimuli } * on vascular muscle (C. Jiang et al.; Acute effect of 178-estradiol on rabbit j 5 coronary artery contractile responses to endothelin-1; Am. J. Physiol., 263 [1992], ; " H271-H275). The inner vascular walls, under the impact of estrogens, release j factors (prostacyclins) which counteract to the buildup of blood clots. Estrogens are additionally indispensable to women for preservation of the bone 10 structure. Their loss may cause osseous degradation (osteoporosis) (C. Christiansen; Prevention and Treatment of Osteoporosis with Hormone Replacement Therapy; Int. J. of Fertil. and Menop. Studies, 38, Suppl. 1 [1993], 45-54). These latter "central nervous" and "metabolic" effects of estrogens are major aspects in HRT, 15 Notwithstanding the numerous appreciable aspects of estrogen therapy, there still are certain unresolved problems which impose limitations on the therapeutic use of estrogens or may entail undesirable effects.
Load more

Recommended publications
  • Hormonal Treatment Strategies Tailored to Non-Binary Transgender Individuals
    Journal of Clinical Medicine Review Hormonal Treatment Strategies Tailored to Non-Binary Transgender Individuals Carlotta Cocchetti 1, Jiska Ristori 1, Alessia Romani 1, Mario Maggi 2 and Alessandra Daphne Fisher 1,* 1 Andrology, Women’s Endocrinology and Gender Incongruence Unit, Florence University Hospital, 50139 Florence, Italy; [email protected] (C.C); jiska.ristori@unifi.it (J.R.); [email protected] (A.R.) 2 Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, 50139 Florence, Italy; [email protected]fi.it * Correspondence: fi[email protected] Received: 16 April 2020; Accepted: 18 May 2020; Published: 26 May 2020 Abstract: Introduction: To date no standardized hormonal treatment protocols for non-binary transgender individuals have been described in the literature and there is a lack of data regarding their efficacy and safety. Objectives: To suggest possible treatment strategies for non-binary transgender individuals with non-standardized requests and to emphasize the importance of a personalized clinical approach. Methods: A narrative review of pertinent literature on gender-affirming hormonal treatment in transgender persons was performed using PubMed. Results: New hormonal treatment regimens outside those reported in current guidelines should be considered for non-binary transgender individuals, in order to improve psychological well-being and quality of life. In the present review we suggested the use of hormonal and non-hormonal compounds, which—based on their mechanism of action—could be used in these cases depending on clients’ requests. Conclusion: Requests for an individualized hormonal treatment in non-binary transgender individuals represent a future challenge for professionals managing transgender health care. For each case, clinicians should balance the benefits and risks of a personalized non-standardized treatment, actively involving the person in decisions regarding hormonal treatment.
    [Show full text]
  • Nandrolone Technical Document July 04 V1.0
    WADA Technical Document – TD2004NA Document Number: TD2004NA Version Number: 1.0 Written by: WADA Laboratory Committee Approved by: WADA Executive Committee Date: 28 May, 2004 Effective Date: 13 August, 2004 REPORTING NORANDROSTERONE FINDINGS 1. Introduction: This document has been established to harmonize analysis and reporting of norandrosterone Adverse Analytical Findings by Laboratories. The administration of 19-norsteroids such as 19-nortestosterone (nandrolone), 19-norandrostene-3,17- dione and 19-norandrostene-3,17-diol (delta-4 and -5 isomers) has been shown to lead mainly to the excretion of 19-norandrosterone (NA), 19-noretiocholanolone (NE) and 19-norepiandrosterone (NEA). The latter is found exclusively as its sulfoconjugate while the others are usually excreted as their glucuronide derivative. The sulfate derivatives, generally persistent, may be prevalent at the end of the excretion period. After the i.m. administration of the long-lasting preparations of nandrolone, the metabolites may be detected for months, but metabolites formed after the oral ingestion are excreted massively in the first hours and remain detectable for only a few days. The excretion of 19-norandrosterone generally predominates that of the 5b-isomer but inversed proportions have been reported in some individuals after oral administration either at the end of the excretion period or when ? 5-isomers of related norsteroids were taken (1). Norandrosterone is excreted during pregnancy and2010 as a minor metabolite of norethisterone (2). Special procedures such as more sensitive instrumentation, larger volumes of urine and more extensive sample clean-up were needed to detect, identify and quantify endogenous 19-norandrosterone (with limits of detection needing to be ten times lower than routine testing i.e.
    [Show full text]
  • Steroids – Basic Science
    STEROIDS – BASIC SCIENCE Edited by Hassan Abduljabbar Steroids – Basic Science Edited by Hassan Abduljabbar Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Bojan Rafaj Technical Editor Teodora Smiljanic Cover Designer InTech Design Team Image Copyright loriklaszlo, 2011. DepositPhotos First published December, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from [email protected] Steroids – Basic Science, Edited by Hassan Abduljabbar p.
    [Show full text]
  • PUBLIC ASSESSMENT REPORT Decentralised Procedure Dienogest
    PUBLIC ASSESSMENT REPORT Decentralised Procedure Dienogest Aristo 2 mg Tabletten Procedure Number: DE/H/5431/001/DC Active Substance: Dienogest Dosage Form: Tablet Marketing Authorisation Holder in the RMS, Germany: Aristo Pharma GmbH Publication: 18.12.2019 This module reflects the scientific discussion for the approval of Dienogest Aristo 2 mg Tabletten. The procedure was finalised on 10.10.2019. TABLE OF CONTENTS I INTRODUCTION ......................................................................................................................... 4 II EXECUTIVE SUMMARY .......................................................................................................... 4 II.1 PROBLEM STATEMENT............................................................................................................... 4 II.2 ABOUT THE PRODUCT ................................................................................................................ 4 II.3 GENERAL COMMENTS ON THE SUBMITTED DOSSIER ............................................................... 5 II.4 GENERAL COMMENTS ON COMPLIANCE WITH GMP, GLP, GCP AND AGREED ETHICAL PRINCIPLES ........................................................................................................................................... 5 III SCIENTIFIC OVERVIEW AND DISCUSSION .................................................................... 6 III.1 QUALITY ASPECTS .................................................................................................................... 6 III.2
    [Show full text]
  • Inhibition of Estrone Sulfate-Induced Uterine Growth by Potent Nonestrogenic Steroidal Inhibitors of Steroid Sulfatase1
    [CANCER RESEARCH 63, 6442–6446, October 1, 2003] Inhibition of Estrone Sulfate-induced Uterine Growth by Potent Nonestrogenic Steroidal Inhibitors of Steroid Sulfatase1 Liviu C. Ciobanu, Van Luu-The, Ce´line Martel, Fernand Labrie, and Donald Poirier2 Medicinal Chemistry Division, Oncology and Molecular Endocrinology Research Center, Centre Hospitalier Universitaire de Que´bec-Pavillon CHUL, and Universite´ Laval, Que´bec, G1V 4G2, Canada ABSTRACT thetic pathway accounts for the transformation of DHEAS into the estrogenic C19 steroid 5-diol. Thus, inhibition of steroid sulfatase, the The present study describes the biological in vitro and in vivo evaluation enzyme responsible for the conversion of DHEAS to dehydroepi- of 2-methoxy derivatives of estrogenic inhibitors of steroid sulfatase, androsterone and E StoE , may allow reduction of estrogen levels in namely 3-sulfamoyloxy-17␣-p-tert-butylbenzyl(or benzyl)-1,3,5 (10)- 1 1 estratrien-17␤-ols. The addition of the 2-methoxy group conserves the tumors and could represent a promising approach for the treatment of estrogen-sensitive breast cancer. potent inhibitory effect on steroid sulfatase activity (IC50s of 0.024 and 0.040 nM) while removing the estrogenic action. Using an ovariectomized Some of the most efficient steroid sulfatase inhibitors developed were mouse model, we show that the first generation of steroid sulfatase inhib- sulfamate derivatives (10–12). The first reported inhibitor in this series, itors tested, 3-sulfamoyloxy-17␣-p-tert-butylbenzyl(or benzyl)estra-1,3,5 estrone sulfamate (EMATE; Ref. 25, 26) is a very potent irreversible (10)-trien-17␤-ols and estrone-3-O-sulfamate, are estrogenic compounds inhibitor, but it is also an estrogenic compound (27), thus having less than stimulating estrogen-sensitive uterine growth.
    [Show full text]
  • Effects of Dienogest, a Synthetic Steroid, on Experimental Endometriosis in Rats
    European Journal of Endocrinology (1998) 138 216–226 ISSN 0804-4643 Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats Yukio Katsuki, Yukiko Takano, Yoshihiro Futamura, Yasunori Shibutani, Daisuke Aoki1, Yasuhiro Udagawa1 and Shiro Nozawa1 Toxicology Laboratory, Mochida Pharmaceutical Co. Ltd, Fujieda, Shizuoka 426, Japan and 1Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160, Japan (Correspondence should be addressed to Y Katsuki, Toxicology Laboratory, Mochida Pharmaceutical Co. Ltd, 342 Gensuke Fujieda, Shizuoka 426, Japan) Abstract Objective: Dienogest, a synthetic steroid with progestational activity, is used as a component of oral contraceptives and is currently being evaluated clinically for the treatment of endometriosis. The present study was conducted to confirm the effects of dienogest on experimental endometriosis in rats and to elucidate its mechanism of action. Design: Experimental endometriosis induced by autotransplantation of endometrium in rats. Methods: Endometrial implants, immune system, and bone mineral were investigated after 3 weeks of medication. Results: Dienogest (0.1–1 mg/kg per day, p.o.) reduced the endometrial implant volume to the same extent as danazol (100 mg/kg per day, p.o.). Simultaneously, dienogest ameliorated the endometrial implant-induced alterations of the immune system; i.e. it increased the natural killer activity of peritoneal fluid cells and splenic cells, decreased the number of peritoneal fluid cells, and decreased interleukin-1b production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 mg/kg per day, s.c.) had none of these immunologic effects. Additionally, combined administration of dienogest (0.1 mg/kg per day) plus buserelin (0.3 mg/kg per day) suppressed the bone mineral loss induced by buserelin alone, with no reduction of the effect on endometrial implants.
    [Show full text]
  • Manfred Ewald Page 1 of 4
    Steven Ungerleider: Saying goodbye to evil: Manfred Ewald Page 1 of 4 FIND A Enter Category » OR Search By Biz Name, Location BUSINESS Home News+Biz Local Sports Forums+Chat Cams+Radio Living Entertainment INSIDE Opinion » Editorials » Win Duck Basketball Tickets! » More From The Oregonian » Commentary » Letters Guest Commentary » Public Comments » Columnists » Jack Ohman Steven Ungerleider: Saying goodbye to evil: » Oregonian Manfred Ewald Archive » Special Reports 11/25/02 FROM OUR ADVERTISERS >> Is your breath too fresh? Try Carl's Jr. Major news organizations including The New York Times, Chicago >> Oregon Coast November Specials! Tribune, and Los Angeles Times offered expanded coverage of the SPEAK UP! >> Thanksgiving dinners delivered to » Town Square your door obituary of Manfred Ewald, the former East German minister of sport, on » Oregon Forum Oct. 23. His death at the age of 76, due to a lung infection, was received » Wild Talk with some fanfare and comment by prominent members of the sports » More Forums » Advertise With Us establishment and media experts. East Germany no longer exists, the » Log On to ChatXtra! Berlin wall fell in 1989 and the country unified with West Germany in NEWSLETTERS 1990. So why the fuss? » Sign up for daily news updates Mr. Ewald, was not just your ordinary, run-of-the-mill sports figure, but in fact, the minister of sport and the president of his nation's Olympic committee for nearly 30 years. He oversaw a sports machine that produced some 500 Olympic medals from a country with only 17 million people. He wore many hats during his 30-year tenure.
    [Show full text]
  • Illegal Manipulation of Your Body
    ES.010 Chemistry of Sports Illegal manipulation of your body Schedule of events for today: 1. Update on workout on Thursday – in the pool 4 pm. 2. Drugs in sports 3. Introduction to Wind tunnel testing – preview of next week’s class with Kim Blair. Drugs in Sports • Blood Doping, Artificial • THG Oxygen Carriers and • Human Chorionic Erythropoietin (EPO) Gonadotrophin (HCG) • Human Growth Hormone • Adrenocorticotropic Hormone • Anabolic Steroids (ACTH) • Insulin-like Growth Factor • Beta-2-Agonists (IGF-1) • Hormone Antagonists and • Cocaine Modulators • Caffeine • Diuretics • Narcotics • Gene Doping • Cannabinoids • Amphetamines Why do Athletes Take Drugs? There are a large number of reasons why an athlete may decide to take drugs. A selection are listed here: • Pressure to succeed, either from themselves or coaches/family and sponsors (major reason) • Belief that their competitors are taking drugs • Pressure from governments/national authorities (as occurred in the eastern bloc countries in the 60's and 70's) • Financial rewards for outstanding performance • Lack of access to, or funding for training facilities and additional support (nutrition, psychological support) • Community and media attitudes and expectations of success Reference:http://www.teachpe.com/drugs/drugs.php. Drugs in Sports • Blood Doping and Erythropoietin • THG (EPO) • Human Chorionic Gonadotrophin • Human Growth Hormone (HCG) • Anabolic Steroids • Adrenocorticotropic Hormone • Insulin-like Growth Factor (IGF- (ACTH) 1) • Beta-2-Agonists • Cocaine • Hormone Antagonists
    [Show full text]
  • Interactions of Nandrolone and Psychostimulant Drugs on Central Monoaminergic Systems
    Sanna Kailanto Sanna Kailanto Interactions of Nandrolone Sanna Kailanto and Psychostimulant Drugs RESEARCH Interactions of Nandrolone and RESEARCH Psychostimulant Drugs on Central on Central Monoaminergic Monoaminergic Systems Systems Monoaminergic Systems Monoaminergic Central on Drugs Psychostimulant and Nandrolone of Interactions This study had four main aims. First, it aimed to explore the effects of nandrolone decanoate on dopaminergic and serotonergic activities in rat brains. Second, it set out to assess whether nandrolone pre-exposure modulates the acute neurochemical and behavioral effects of psychostimulant drugs in experimental animals. A third aim was to investigate if AAS-pretreatment-induced changes in brain reward circuitry are reversible. Finally, the study was also intended to evaluate the role of androgen receptors in nandrolone’s ability to modulate the dopaminergic and serotonergic effects of stimulants. The results of the study show that AAS pretreatment inhibits the reward- related neurochemical and behavioral effects of amphetamine, MDMA and cocaine in experimental animals. Given that LMA, stereotyped behavior and accumbal outflow of DA and 5-HT are all related to reward, this study suggests that nandrolone, at tested doses, significantly affects the rewarding properties of stimulant drugs. Furthermore, it seems that these effects could be long- lasting and that the ability of nandrolone to modulate reward-related effects of stimulants depends on AR or ER activation. .!7BC5<2"HIFILD! National Institute for Health and Welfare P.O. Box 30 (Mannerheimintie 166) FI-00271 Helsinki, Finland Telephone: +358 20 610 6000 30 ISBN 978-952-245-258-0 www.thl.fi 30 2010 30 Sanna Kailanto Interactions of Nandrolone and Psychostimulant Drugs on Central Monoaminergic Systems Academic disSertAtIoN To be presented with the permission of the Faculty of Biological and Environmental Sciences, University of Helsinki, for public examination in the Arppeanum auditorium, Helsinki University Museum, Snellmaninkatu 3, Helsinki, on April 29nd, at 12 o’clock noon.
    [Show full text]
  • Estradiol Prodrugs (EP) for Efficient Oral Estrogen Treatment And
    Journal of Steroid Biochemistry & Molecular Biology 165 (2017) 305–311 Contents lists available at ScienceDirect Journal of Steroid Biochemistry & Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions a d a a a a e W. Elger , R. Wyrwa , G. Ahmed , F. Meece , H.B. Nair , B. Santhamma , Z. Killeen , a c b a, B. Schneider , R. Meister , H. Schubert , K. Nickisch * a Evestra, Inc., 14805 Omicron Drive, Suite 100, San Antonio, TX 78245, USA b Friedrich Schiller University Jena, Fürstengraben 1, 07743 Jena, Germany c Beuth University of Applied Science, Luxemburger Str. 10, 13353 Berlin, Germany d Innovent e.V., Prüssingstraße 27B, 07745 Jena, Germany e University of Arizona College of Medicine, 1501 N Campbell Ave, Tucson, AZ 85724, USA A R T I C L E I N F O A B S T R A C T Article history: Received 23 March 2016 Oral compared to parenteral estrogen administration is characterized by reduced systemic but Received in revised form 15 July 2016 prominent hepatic estrogenic effects on lipids, hemostatic factors, GH-/IGF I axis, angiotensinogen. In Accepted 18 July 2016 order to avoid such adverse metabolic effects of oral treatment, estradiol (E2) prodrugs (EP) were Available online 20 July 2016 designed which bypass the liver tissue as inactive molecules. Carbone17-OH sulfonamide [-O2–NH2] substituted esters of E2 (EC508, others) were synthesized and tested for carbonic anhydrase II (CA-II) Keywords: binding. CA II in erythrocytes is thought to oppose extraction of EP from portal vein blood during liver COC (combined oral contraceptives) passage.
    [Show full text]
  • Évaluation Biologique in Vitro D'inhibiteurs De La Stéroïde Sulfatase
    Évaluation biologique in vitro d’inhibiteurs de la stéroïde sulfatase ayant un effet SERM Mémoire Charles Ouellet Maîtrise en physiologie-endocrinologie Maître ès sciences (M.Sc.) Québec, Canada © Charles Ouellet, 2013 Résumé Initialement, les cancers du sein sont majoritairement hormonodépendants, c’est-à-dire qu’ils sont stimulés par les hormones estrogéniques endogènes. Une première approche pour traiter ce type de cancer consiste à utiliser un antiestrogène pour bloquer l’activation du récepteur des estrogènes dans le tissu mammaire. Une seconde approche consiste à inhiber la synthèse des estrogènes par l’utilisation d’inhibiteurs spécifiques pour certaines enzymes clés de la stéroïdogénèse. La stéroïde sulfatase (STS), une enzyme impliquée dans la biosynthèse des estrogènes, constituerait une importante cible thérapeutique. Dans le cadre de ce mémoire, je discuterai d’un nouveau projet de recherche qui consiste à développer des composés à double-action combinant les deux types d’approches nommées précédemment. Nous cherchons à développer une molécule non-stéroïdienne qui serait en mesure d’inhiber la STS mais également de bloquer le récepteur des estrogènes dans le tissu mammaire. Notre composé doit donc posséder un effet SERM (Selective Estrogen Receptor Modulator), c’est-à-dire de jouer le rôle d’un antagoniste dans le tissu mammaire tout en jouant le rôle d’un agoniste dans d’autres tissus (i.e. tissu osseux) où l’action des estrogènes est importante. Dans ce mémoire, j’aborderai rapidement la synthèse chimique des deux générations de composés pour m’attarder davantage sur les tests biologiques in vitro nécessaires à l’évaluation de leur potentiel à double-action.
    [Show full text]
  • New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies
    molecules Article New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies Catarina Canário 1 , Mariana Matias 1, Vanessa Brito 1, Adriana O. Santos 1, Amílcar Falcão 2,3 , Samuel Silvestre 1,4,* and Gilberto Alves 1 1 CICS-UBI–Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal; [email protected] (C.C.); [email protected] (M.M.); [email protected] (V.B.); [email protected] (A.O.S.); [email protected] (G.A.) 2 Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; [email protected] 3 CIBIT-Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, 3000-548 Coimbra, Portugal 4 CNC–Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal * Correspondence: [email protected] Abstract: The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehy- drogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher Citation: Canário, C.; Matias, M.; Brito, V.; Santos, A.O.; Falcão, A.; cytotoxicity than the parent compound on MCF-7 cancer cells.
    [Show full text]