DOCSLIB.ORG

Ep 3311667 A1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Ep 3311667 A1 (19) TZZ¥¥___T (11) EP 3 311 667 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 25.04.2018 Bulletin 2018/17 A01N 43/42 (2006.01) A61K 31/44 (2006.01) (21) Application number: 17194444.0 (22) Date of filing: 08.07.2010 (84) Designated Contracting States: • SCHACHTEL, Bernard AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Jupiter, FL Florida 33477 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • TAKIGIKU, Ray PL PT RO SE SI SK SM TR Loveland, OH Ohio 45140 (US) (30) Priority: 08.07.2009 US 223999 P (74) Representative: Avidity IP 09.07.2009 US 224424 P Broers Building Hauser Forum (62) Document number(s) of the earlier application(s) in 21 JJ Thomson Avenue accordance with Art. 76 EPC: Cambridge CB3 0FA (GB) 10797879.3 / 2 451 274 Remarks: (71) Applicant: Charleston Laboratories, Inc. •This application was filed on 02-10-2017 as a Jupiter, FL 33477 (US) divisional application to the application mentioned under INID code 62. (72) Inventors: •Claims f iled aft er the date of fil ing of the • BOSSE, Paul application/after the date of receipt of the divisional Jupiter, FL Florida 33469 (US) application (Rule 68(4) EPC) • AMELING, John Cincinnati, OH 45252-1051 (US) (54) PHARMACEUTICAL COMPOSITIONS (57) Methods and compositions are provided which comprise effective amounts of analgesic to treat a subject, including reducing or eliminating an adverse effect associated with the analgesic. EP 3 311 667 A1 Printed by Jouve, 75001 PARIS (FR) EP 3 311 667 A1 Description CROSS-REFERENCE 5 [0001] This application claims the benefit of U.S. Provisional Application No. 61/223,999, filed July 8, 2009, and U.S. Provisional Application No. 61/224,424, filed July 9, 2009, which are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION 10 [0002] Available pain medications may have adverse effects, such as nausea, vomiting, and skin rashes and sedation. As a result of such adverse effects, many subjects are unable to tolerate recommended dosages needed for effective pain relief because of adverse effects. Accordingly, there remains a need for effective therapeutics with reduced adverse effects. 15 INCORPORATION BY REFERENCE [0003] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. 20 SUMMARY OF THE INVENTION [0004] In one aspect, provided herein is a bi-layer tablet comprising: (1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 135 mg to 25 about 170 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 20 mg of hydroxy methyl propyl cellulose, (d) about 10 mg of croscarmellose sodium (e) from about 1 mg to about 4 mg of magnesium stearate, (f) from about 1mg to about 4 mg of stearic acid, and (g) from about 250 mg to about 402 mg of acetaminophen or a pharma- ceutically acceptable salt thereof; and (2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified 30 microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate. In one embodiment the controlled-release layer comprises about 7.5 mg of hy- drocodone or a pharmaceutically acceptable salt thereof; and wherein the immediate-release layer comprises about 12.5 mg of promethazine or a pharmaceutically acceptable salt thereof. In another embodiment, the controlled-release layer further comprises about 325 mg of acetaminophen or a pharmaceutically acceptable salt thereof. In another 35 embodiment, the tablet has a hardness of about 9.5 kilopond and thickness from about 6.9 to about 7.0 mm. In another embodiment, the hydrocodone salt is hydrocodone bitartrate. In another embodiment, the promethazine salt is promet- hazine HCl. In another embodiment, the effective amount of the hydrocodone or pharmaceutically acceptable salt thereof is an amount effective for treating or preventing pain for a period of 8-12 hours immediately following administration to a subject. In another embodiment, the controlled release layer is formulated to release in a subject in need thereof said 40 hydrocodone or a pharmaceutically acceptable salt thereof, or said acetaminophen or a pharmaceutically acceptable salt thereof at a rate that maintains a higher blood plasma level of said hydrocodone or a pharmaceutically acceptable salt thereof or said acetaminophen or a pharmaceutically acceptable salt for 4-8 hours compared to the blood plasma level after administration of an equivalent dosage of hydrocodone or a pharmaceutically acceptable salt thereof or acetaminophen or a pharmaceutically acceptable salt thereof in a non-controlled release formulation. In another em- 45 bodiment, the immediate release layer is formulated to release, after administration in a subject in need thereof, said promethazine or a pharmaceutically acceptable salt thereof at a rate that produces a peak plasma concentration of promethazine or a pharmaceutically acceptable salt thereof in the subject’s blood about 30-120 minutes earlier compared to peak plasma concentrations after administration to the subject of an equivalent dosage of promethazine or a phar- maceutically acceptable salt thereof in a non-immediate-release formulation. In another embodiment, the promethazine 50 or a pharmaceutically acceptable salt thereof potentiates the analgesic effect of said hydrocodone or a pharmaceutically acceptable salt thereof or said acetaminophen or a pharmaceutically acceptable salt thereof. [0005] In another aspect, provided herein is a method for treating or preventing pain comprising, administering to a subject in need thereof a bi-layer tablet comprising: (1) a controlled- release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 250 to about 402 mg of 55 acetaminophen or a pharmaceutically acceptable salt thereof, (c) from about 135 mg to about 170 mg of silicified microcrystalline cellulose, (d) from about 12 mg to about 20 mg of hydroxy methyl propyl cellulose, (e) from about 1 mg to about 4 mg of magnesium stearate (f) from about 1mg to about 4 mg of stearic acid, and (g) about 10 mg of croscar- mellose sodium; and(2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine 2 EP 3 311 667 A1 or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate. [0006] In another aspect, provided herein is a method for treating or preventing pain comprising, administering to a 5 subject in need thereof a bi-layer tablet comprising: (1) a controlled- release layer comprising about 7.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, about 325 mg of acetaminophen or a pharmaceutically acceptable salt thereof, about 149.5 mg of silicified microcrystalline cellulose, about 15.5 mg of hydroxy methyl propyl cellulose, about 10 mg of croscarmellose sodium, about 2.7 mg of magnesium stearate, and about 2.7 mg of stearic acid; and (2) an immediate release layer comprising about 12.5 mg of promethazine or a pharmaceutically acceptable salt thereof, about 10 121.5 mg of silicified microcrystalline cellulose, about 15 mg of croscarmellose sodium and about 1 mg of magnesium stearate. [0007] In another aspect, provided herein is a bi-layer tablet comprising: (1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 135 mg to about 170 mg of silicified microcrystalline cellulose, (c) about 15.7 mg of hydroxy methyl propyl cellulose, (d) about 15 10 mg of croscarmellose sodium (e) from about 1 mg to about 4 mg of magnesium stearate, (f) from about 1mg to about 4 mg of stearic acid, and from about 250 mg to about 402 mg of acetaminophen or a pharmaceutically acceptable salt thereof; and (2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium 20 stearate. [0008] In another aspect, provided herein is a bi-layer tablet, comprising a a controlled-release layer and an immediate release layer, wherein the controlled-release layer comprises about 7.5 mg of hydrocodone or a pharmaceutically ac- ceptable salt thereof, about 325 mg of acetaminophen or a pharmaceutically acceptable salt thereof, about 149.5 mg of silicified microcrystalline cellulose, about 15mg to 16 mg of hydroxy methyl propyl cellulose, about 9.5mg to 10.5 mg 25 of croscarmellose sodium, about 2.7 mg of magnesium stearate, and about 2.7 mg of stearic acid; and the immediate release layer comprises about 12.5 mg of promethazine or a pharmaceutically acceptable salt thereof, about 121.5 mg of silicified microcrystalline cellulose, about 15 mg of croscarmellose sodium and about 1 mg of magnesium stearate.
Load more

Recommended publications
  • DART-MS/MS Screening for the Determination of 1,3- Dimethylamylamine and Undeclared Stimulants in Seized Dietary Supplements from Brazil
    Forensic Chemistry 8 (2018) 134–145 Contents lists available at ScienceDirect Forensic Chemistry journal homepage: www.elsevier.com/locate/forc DART-MS/MS screening for the determination of 1,3- dimethylamylamine and undeclared stimulants in seized dietary supplements from Brazil Maíra Kerpel dos Santos a, Emily Gleco b, J. Tyler Davidson b, Glen P. Jackson b, Renata Pereira Limberger a, ⇑ Luis E. Arroyo b, a Graduate Program of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Brazil b Department of Forensic & Investigative Science, West Virginia University, USA article info abstract Article history: 1,3-dimethylamylamine (DMAA) is an alkylamine with stimulating properties that has been used pre- Received 15 December 2017 dominantly as an additive in dietary supplements. DMAA is mostly consumed by professional athletes, Received in revised form 14 March 2018 and several doping cases reported since 2008 led to its prohibition by the World Anti-Doping Agency Accepted 18 March 2018 (WADA) in 2010. Adverse effects have indicated DMAA toxicity, and there is few data regarding its safety, Available online 22 March 2018 so it was banned by regulatory agencies from Brazil and the United States. Ambient ionization methods such as Direct Analysis in Real Time Tandem Mass Spectrometry (DART-MS/MS) are an alternative for Keywords: dietary supplements analysis, because they enable the analysis of samples at atmospheric pressure in 1,3-dimethylamylamine a very short time and with only minimal sample preparation. Therefore, the aim of this work was to DART-MS/MS Dietary supplements develop a methodology by DART-MS/MS to detect the presence of DMAA, ephedrine, synephrine, caffeine, Stimulants sibutramine, and methylphenidate in 108 dietary supplements seized by the Brazilian Federal Police Adulterants (BFP).
    [Show full text]
  • Multi-Class Determination of 64 Illicit Compounds in Dietary Supplements Using Liquid Chromatography–Tandem Mass Spectrometry
    molecules Article Multi-Class Determination of 64 Illicit Compounds in Dietary Supplements Using Liquid Chromatography–Tandem Mass Spectrometry Dasom Shin, Hui-Seung Kang *, Hyungsoo Kim and Guiim Moon New Hazardous Substances Division, Department of Food Safety Evaluation, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju 28159, Korea; [email protected] (D.S.); [email protected] (H.K.); [email protected] (G.M.) * Correspondence: [email protected] Received: 11 August 2020; Accepted: 17 September 2020; Published: 24 September 2020 Abstract: In this work, liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated for screening and confirmation of 64 illicit compounds in dietary supplements. The target compounds were illegally used pharmaceutical drugs, prohibited compounds, and not authorized ingredients for different therapeutics (sexual enhancement, weight loss, muscular strengthening, and relaxing products). The validation procedure was performed to evaluate selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision according to the Association of Official Analytical Chemists guidelines. The linearity was >0.98 in the range of 1 1 0.5–200 µg L− . The LOQs were in the range 1–10 µg kg− for all target compounds. The accuracy (expressed as recovery) was 78.5–114%. The precision (expressed as the relative standard deviation) was below 9.15%. The developed method was applied for the determination of illicit compounds in dietary supplements collected from websites. As a result, the total detection rate was 13.5% (27 samples detected in 200 samples). The concentrations of detected samples ranged from 0.51 1 to 226 mg g− .
    [Show full text]
  • Stimulant Medications and Supplements: Clinical Implications for the Sports Medicine Provider Collaborative Solutions for Safety in Sport
    Stimulant Medications and Supplements: Clinical Implications for the Sports Medicine Provider Collaborative Solutions for Safety in Sport Francis G. O’Connor, MD, MPH, COL, MC, USA Professor and Chair, Military and Emergency Medicine Uniformed Services University of the Health Sciences DISCLOSURE . I have no relevant financial disclosures in reference to this lecture. That being said, I am a physician in the US Army, and work for the DoD. My opinions and assertions contained herein are private views and are not to be construed as official or as reflecting the views of the U.S. Army Medical Department , Uniformed Services University or the Department of Defense at large. Case Presentation 1 . 25 y/o soldier presents to the sports medicine clinic for heat tolerance testing and a return to duty assessment; . He sustained an exertional heat stroke (EHS) during Special Forces accession. Soldier was acclimatized with no history of EHS; he had been using a pre- workout stimulant. Case Presentation 2 . 25 y/o soldier presents to the medical aid station complaining of palpitations, agitation and insomnia. He has sinus tachycardia on the monitor and reports regular use of Red Bull and caffeine gum. Unit is requesting guidance on strategies for sleep. Case Presentation 3 . A warfighter contacts the Human Performance Resource Center looking for help. Recently using a new pre- workout supplement to enhance training. Unfortunately the soldier “popped positive” on a recent urine drug screen. Case Presentation 4 . Alison is a 19 y/o transfer female basketball player. She states she has a personal history of ADHD and would like to renew her prescription for Ritalin.
    [Show full text]
  • Chiral Separation for Enantiomeric Determination in the Pharmaceutical Industry
    Chapter CHIRAL SEPARATION FOR ENANTIOMERIC DETERMINATION IN THE PHARMACEUTICAL INDUSTRY Nelu Grinberg, Su Pan Contents 6.1. INTRODUCTION ...................................................................................................................................... 235 6.2. ENANTIOMERS, DIASTEREOMERS, RACEMATES ................................................................... 236 6.3. REQUIREMENTS FOR CHIRAL SEPARATION ............................................................................ 237 6.4. THE TYPES OF MOLECULAR INTERACTIONS ........................................................................... 237 6.4.1. Chiral separation through hydrogen bonding ............................................................. 237 6.4.2. Chiral separation through inclusion compounds ....................................................... 243 6.4.2.1. Cyclodextrins ............................................................................................................ 243 6.4.2.2. Crown ethers ............................................................................................................. 245 6.4.3. Charge transfer .......................................................................................................................... 259 6.4.4. Chiral separation through a combination of charge transfer, hydrogen bonding and electrostatic interactions ........................................................................... 260 233 Chapter 6 6.4.5. Ligand exchange ......................................................................................................................
    [Show full text]
  • Methedrine, Neo-Synephrine, Paredrine, and Pholedrine
    Br Heart J: first published as 10.1136/hrt.6.4.214 on 1 October 1944. Downloaded from CLINICAL EVALUATION OF THE PRESSOR ACTIVITY OF METHEDRINE, NEO-SYNEPHRINE, PAREDRINE, AND PHOLEDRINE BY FREDERICK PRESCOTT From the Wellcome Research Institution, London Received October 10, 1944 Recently a number of pressor drugs of the adrenaline type have come into clinical use for the treatment of low blood pressure following surgical procedures, spinal anxsthesia, circu- latory collapse, and surgical and traumatic shock. For therapeutic purposes the ideal pressor drug should be effective by the intramuscular or intravenous route; it should act rapidly; it should produce a sustained elevation of blood pressure, so that frequent injections of the drug are not necessary; and it should have no undesirable effects on the cardiovascular system and no untoward side effects. Adrenaline and ephedrine were the first drugs to be used clinically to raise the blood pressure in cases of operative shock. Their limitations, however, are nowv well known. Adrenaline may do more harm than good beca4se in thera- peutic doses intrayenously it causes a considerable rise of blood pressure, e.g. 200 mm. to 300 mm. of mercury, with a precipitous fall after a few minutes to a level lower than before. Similarly ephedrine, which for dependable results must be given intravenously, produces a http://heart.bmj.com/ sharp rise of blood pressure that lasts only for ten to twenty minutes. Other pressor drugs have been introduced with a more sustained action. In most of the studies reported on these, however, no definite criteria seem to have been employed in their evaluation, nor have the conditions of administration been standardized.
    [Show full text]
  • Guidelines for the Use of Synephrine in Natural Health Products
    -Notice- Guidelines for the Use of Synephrine in Natural Health Products January 2010 The Natural Health Products Directorate (NHPD) has conducted a review of the safety of synephrine, a substance which has structural resemblance to epinephrine and ephedrine. Based on the potential for cardiovascular toxicity, the NHPD has adopted the following guidelines for the use of synephrine in Natural Health Products. • A limit of 30 mg/day has been adopted as the maximum allowable dose for total synephrine and octopamine, which is related chemically and pharmacologically to synephrine. Sources of these substances include Citrus species such as C. aurantium, as well as certain species of some other genera (e.g. Evodia rutaecarpa), and synthetic sources. The above limit is consistent with that adopted by the Australian Therapeutic Goods Administration for synephrine in over-the-counter products (NDPSC 2003). • Given that there is currently insufficient published clinical evidence to establish a safe level for synephrine + caffeine combinations, caffeine or caffeine sources (e.g. coffee, tea, cola, maté, guarana) will not be permitted in synephrine-containing products without submission of sufficient clinical evidence in humans. • As there is insufficient information to establish the safety of long-term use of synephrine-containing products, a duration-of-use statement is required: Consult a health care practitioner for use beyond 8 weeks (Greenway et al. 2006). Risk Information: • No risk information is required for products providing ≤ 3 mg synephrine + octopamine in a daily dose. This is based on a long history of safe use of bitter orange in Traditional Chinese Medicine at doses that provide approximately 3 mg/day synephrine.
    [Show full text]
  • Alltech® Drug Standards for the Forensic, Clinical & Pharmaceutical Industries OH
    Alltech® Drug Standards For the Forensic, Clinical & Pharmaceutical Industries OH H3C H H H3C H HO Catalog #505B Our Company Welcome to the Grace's Alltech® Drug Standards Catalog W. R. Grace has manufactured high-quality silica for over 150 years. Grace has been behind the scenes for the past 30 years supplying silica to the chromatography industry. Now we’re in the forefront moving beyond silica, developing and delivering innovative complementary products direct to the customer. Grace Davison Discovery Sciences was founded on Grace’s core strength as a premier manufacturer of differentiated media for SPE, Flash, HPLC, and Process chromatography. This core competency is further enhanced by bringing seven well-known global separations companies together, creating a powerful new single source for all your chromatography needs. A Full Portfolio of Chromatography Products to Support Drug Standards: • HPLC Columns • HPLC Accessories • Flash Products • TLC Products • GC Columns • GC Accessories • SPE and Filtration • Equipment • Syringes • Tubing • Vials For complete details, download the Chromatography Essentials catalog from the Grace web site or contact your customer service representative. Alltech - Part of the Grace Family of Products In 2004, Alltech Associates Inc. was acquired by Grace along with the Alltech® Drug Standards product line. Through investment in research and strategic acquisitions, Grace has expanded our product range and global reach while drawing upon the support of the Grace corporate infrastructure and more than 6000 employees globally to support scientific research and analysis worldwide. With key manufacturing sites in North and South America, Europe, and Asia, plus an extensive international sales and distribution network, separation scientists throughout the world can count on timely delivery and expert local technical service.
    [Show full text]
  • History Full Circle: 'Novel' Sympathomimetics in Supplements
    Drug Testing Perspective and Analysis Received: 8 July 2015 Revised: 13 July 2015 Accepted: 15 July 2015 Published online in Wiley Online Library: 2 November 2015 (www.drugtestinganalysis.com) DOI 10.1002/dta.1852 History full circle: ‘Novel’ sympathomimetics in supplements Nicolas Rasmussena* and Peter H. J. Keizersb Since the banning of ephedrine in over-the-counter nutritional supplements a decade ago, a plethora of untested and/or unsafe sympathomimetic stimulants have taken its place. This paper argues that these ‘novel’ stimulants in supplements recapitulate the work of synthetic chemists at commercial pharmaceutical firms during the 1930s and 1940s, all seeking substitutes for recently successful products based on ephedrine and amphetamine. Copyright © 2015 John Wiley & Sons, Ltd. Keywords: nutritional supplements; amphetamines; ephedrine; pharmaceutical regulation; drug safety; substance abuse In the 1920s ephedrine (compound (7) in Table 1 and Figure 1) methamphetamine (6), which was unpatentable (because of the brought a new era in commercial pharmacology. Extracted from publication of its 1919 synthesis and pharmacological characteriza- the Chinese herb Ephedra spp. and characterized to great acclaim tion, in the course of structural studies on ephedrine, by Japanese by elite pharmacologists Ko Kuei Chen and Carl Schmidt, the drug chemist Akira Ogata).[3,7] These methamphetamine products in- exhibited a range of adrenaline-like actions – but in a more useful cluded Pervitin tablets from the German firm Temmler and Methe- form than adrenaline, the hormone blockbuster of 1901.[1–3] drine tablets from Burroughs-Wellcome, and the Drinalfa Inhaler Adrenaline (as the substance was then known, but now as a from Squibb.
    [Show full text]
  • The 2004 "Research on Drug Evidence" Report
    The 2004 “Research on Drug Evidence” Report [From the 14th ICPO / INTERPOL Forensic Science Symposium] Robert F. X. Klein*, Melanie E. Domagala, and Patrick A. Hays U.S. Department of Justice Drug Enforcement Administration Special Testing and Research Laboratory 22624 Dulles Summit Court Dulles, VA 20166 [[email protected]] ABSTRACT: A reprint of the 2004 “Research on Drug Evidence” Report (a review) is provided. KEYWORDS: INTERPOL, Illicit Drugs, Controlled Substances, Forensic Chemistry. Important Information: Presented at the 14th ICPO / INTERPOL Forensic Science Symposium, Lyon, France, October 19 - 22, 2004. Authorized Reprint. Copyright INTERPOL. All rights reserved. May not be reprinted without express permission from INTERPOL. For pertinent background, see: Klein RFX. ICPO / INTERPOL Forensic Science Symposia, 1995 - 2016. “Research on Drug Evidence”. Prefacing Remarks (and a Request for Information). Microgram Journal 2016;13(1-4):1-3. Citations in this report from the Journal of the Clandestine Laboratory Investigating Chemists Association and Microgram were (and remain) Law Enforcement Restricted. Microgram was split into Microgram Bulletin and Microgram Journal in 2002 and 2003, respectively; except for the 2002 Bulletins, both the Bulletin and Journal were (and are) unclassified. The “General Overview” (Talking Paper) was removed from this reprint (Editor’s discretion). This reprint is derived from the original electronic document, and is not an image of the best available hard copy (as was utilized for the 1995 and 1998 reports). For this reason, the pagination in the original document is not retained in this reprint, and some minor reformatting was done to eliminate deadspace. Microgram Journal 2016, Volume 13; Numbers 1-4 171 Research On Drug Evidence July 1, 2001 - June 30, 2004 Presented by: Robert F.X.
    [Show full text]
  • Pharmacology of Stimulants Prohibited by the World Anti-Doping Agency (WADA)
    British Journal of Pharmacology (2008) 154, 606–622 & 2008 Nature Publishing Group All rights reserved 0007– 1188/08 $30.00 www.brjpharmacol.org REVIEW Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA) JR Docherty Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland This review examines the pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). Stimulants that increase alertness/reduce fatigue or activate the cardiovascular system can include drugs like ephedrine available in many over- the-counter medicines. Others such as amphetamines, cocaine and hallucinogenic drugs, available on prescription or illegally, can modify mood. A total of 62 stimulants (61 chemical entities) are listed in the WADA List, prohibited in competition. Athletes may have stimulants in their body for one of three main reasons: inadvertent consumption in a propriety medicine; deliberate consumption for misuse as a recreational drug and deliberate consumption to enhance performance. The majority of stimulants on the list act on the monoaminergic systems: adrenergic (sympathetic, transmitter noradrenaline), dopaminergic (transmitter dopamine) and serotonergic (transmitter serotonin, 5-HT). Sympathomimetic describes agents, which mimic sympathetic responses, and dopaminomimetic and serotoninomimetic can be used to describe actions on the dopamine and serotonin systems. However, many agents act to mimic more than one of these monoamines, so that a collective term of monoaminomimetic may be useful. Monoaminomimietic actions of stimulants can include blockade of re-uptake of neurotransmitter, indirect release of neurotransmitter, direct activation of monoaminergic receptors. Many of the stimulants are amphetamines or amphetamine derivatives, including agents with abuse potential as recreational drugs.
    [Show full text]
  • Transcriptome Profiling in Ephedra Sinica and Catha Edulis Reveals Enzymes Putatively Involved in Ephedrine Alkaloid Biosynthesis
    University of Calgary PRISM: University of Calgary's Digital Repository Graduate Studies The Vault: Electronic Theses and Dissertations 2016-01-14 Transcriptome Profiling in Ephedra sinica and Catha edulis Reveals Enzymes Putatively Involved in Ephedrine Alkaloid Biosynthesis Groves, Ryan A Groves, R. A. (2016). Transcriptome Profiling in Ephedra sinica and Catha edulis Reveals Enzymes Putatively Involved in Ephedrine Alkaloid Biosynthesis (Unpublished master's thesis). University of Calgary, Calgary, AB. doi:10.11575/PRISM/28507 http://hdl.handle.net/11023/2747 master thesis University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. Downloaded from PRISM: https://prism.ucalgary.ca UNIVERSITY OF CALGARY Transcriptome Profiling in Ephedra sinica and Catha edulis Reveals Enzymes Putatively Involved in Ephedrine Alkaloid Biosynthesis by Ryan Alexander Groves A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE GRADUATE PROGRAM IN BIOLOGICAL SCIENCES CALGARY, ALBERTA JANUARY, 2016 © Ryan Alexander Groves 2016 Abstract Amphetamine analogs are a class of medicinal compounds produced by Ephedra sinica and Catha edulis. Two commonly used members of this class of compounds include the cough suppressant (1S-2S)-pseudoephedrine, and the stimulant (1R-2S)-ephedrine. These secondary metabolites are produced in planta through a L-phenylalanine derived multi-step pathway. Despite the importance of this biosynthetic pathway, only one enzyme in the pathway has been characterized at the molecular level.
    [Show full text]
  • Bitter Orange Peel and Synephrine
    American Botanical Council Bitter Orange Peel and Synephrine The following article is reprinted with permission from WholeFoods. Part 1 was published in the March 2004 issue of WholeFoods. Part 2 was published in the March 2005 issue. ©2005 American Botanical Council It was not printed or reprinted in HerbClip or HerbalGram, but we offer it to our readers as a web-only exclusive. Bitter Orange Peel and Synephrine: Part 1 Reprinted with permission from WholeFoods March 2004 issue (Part 2, published in March 2005 follows on this page). ©2005 American Botanical Council. By Mark Blumenthal The announcement in late December by the U.S. Food and Drug Administration (FDA) that it intends to issue regulations banning the sale of dietary supplements containing the controversial herb ephedra (Ephedra sinica) has stimulated a flurry of media articles about the sale, potential safety risks, and need for additional regulation of so-called “ephedra-free” dietary supplements and alternatives to ephedra supplements.* Articles on this subject have appeared in The New York Times, USA Today, the Los Angeles Times, Time magazine, and many other publications and electronic news outlets (e.g., CNN, major television networks and local newscasts) about these alternative products. I have been interviewed by many of the above in the two weeks subsequent to the FDA’s announcement of the proposed ban, as well as during the past year. One of the most frequently mentioned ingredients in all of these stories is bitter orange peel and its primary alkaloid, synephrine. During this post-ephedra ban announcement period, bitter orange has become increasingly controversial.
    [Show full text]