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Investigating Interactions Between Phentermine, Dexfenfluramine, and 5-HT2C Agonists, on Food Intake in the Rat
Psychopharmacology DOI 10.1007/s00213-014-3829-2 ORIGINAL INVESTIGATION Investigating interactions between phentermine, dexfenfluramine, and 5-HT2C agonists, on food intake in the rat Andrew J. Grottick & Kevin Whelan & Erin K. Sanabria & Dominic P. Behan & Michael Morgan & Carleton Sage Received: 2 October 2014 /Accepted: 20 November 2014 # The Author(s) 2014. This article is published with open access at Springerlink.com Abstract Conclusions Dex-phen synergy in the rat is caused by a Rationale Synergistic or supra-additive interactions between pharmacokinetic interaction, resulting in increased central the anorectics (dex)fenfluramine and phentermine have been concentrations of phentermine. reported previously in the rat and in the clinic. Studies with 5- HT2C antagonists and 5-HT2C knockouts have demonstrated Keywords Synergy . BELVIQ® . Lorcaserin . Isobologram . dexfenfluramine hypophagia in the rodent to be mediated by Fen-phen actions at the 5-HT2C receptor. Given the recent FDA approv- al of the selective 5-HT2C agonist lorcaserin (BELVIQ®) for weight management, we investigated the interaction between Introduction phentermine and 5-HT2C agonists on food intake. Objectives This study aims to confirm dexfenfluramine- Fenfluramine (Pondimin) and dexfenfluramine (Redux) are phentermine (dex-phen) synergy in a rat food intake assay, anorectic agents which act to enhance serotonergic transmission to extend these findings to other 5-HT2C agonists, and to both through inhibition of 5-HT reuptake by the parent com- determine whether pharmacokinetic interactions could ex- pounds, and through their major circulating des-ethylated me- plain synergistic findings with particular drug combinations. tabolite, (dex)norfenfluramine, which is a 5-HT reuptake inhib- Methods Isobolographic analyses were performed in which itor, a 5-HT and noradrenaline releasing agent, and a potent phentermine was paired with either dexfenfluramine, the 5- agonist at postsynaptic 5-HT2 receptors (Curzon et al. -
Medical Review Officer Manual
Department of Health and Human Services Substance Abuse and Mental Health Services Administration Center for Substance Abuse Prevention Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs EFFECTIVE OCTOBER 1, 2010 Note: This manual applies to Federal agency drug testing programs that come under Executive Order 12564 dated September 15, 1986, section 503 of Public Law 100-71, 5 U.S.C. section 7301 note dated July 11, 1987, and the Department of Health and Human Services Mandatory Guidelines for Federal Workplace Drug Testing Programs (73 FR 71858) dated November 25, 2008 (effective October 1, 2010). This manual does not apply to specimens submitted for testing under U.S. Department of Transportation (DOT) Procedures for Transportation Workplace Drug and Alcohol Testing Programs (49 CFR Part 40). The current version of this manual and other information including MRO Case Studies are available on the Drug Testing page under Medical Review Officer (MRO) Resources on the SAMHSA website: http://www.workplace.samhsa.gov Previous Versions of this Manual are Obsolete 3 Table of Contents Chapter 1. The Medical Review Officer (MRO)........................................................................... 6 Chapter 2. The Federal Drug Testing Custody and Control Form ................................................ 7 Chapter 3. Urine Drug Testing ...................................................................................................... 9 A. Federal Workplace Drug Testing Overview.................................................................. -
(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. -
Reflections on Contagious Off-Label Use of Phentermine and Fenfluramine
University of Massachusetts Medical School eScholarship@UMMS Population and Quantitative Health Sciences Publications Population and Quantitative Health Sciences 2008 Weighing in 10 Years Later: Reflections on Contagious Off-Label Use of Phentermine and Fenfluramine Regina C. Grebla Brown University Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/qhs_pp Part of the Bioinformatics Commons, Biostatistics Commons, Epidemiology Commons, and the Health Services Research Commons Repository Citation Grebla RC, Waring ME. (2008). Weighing in 10 Years Later: Reflections on Contagious Off-Label Use of Phentermine and Fenfluramine. Population and Quantitative Health Sciences Publications. Retrieved from https://escholarship.umassmed.edu/qhs_pp/379 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Population and Quantitative Health Sciences Publications by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Looking Back, Learning Forward History doesn’t repeat itself -- at best it sometimes rhymes. Mark Twain Weighing in 10 years later: Reflections on Contagious off-label use of Phentermine and Fenfluramine Contributed by Regina C. Grebla, MGA, MPH PhD(c) Molly E. Waring AM PhD(c) Graduate students, Brown Medical School The piece for this edition of Scribe focuses on the phentermine and fenfluramine story. This edition comes to you from two students in my advanced pharmacoepidemiology course, shortened significantly to meet the needs of this column. I welcome contributions which stay true to the theme of reflecting and learning about past challenges in pharmacoepidemiology. Please forward ideas to : [email protected] . -
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol Drug Abuse and Mental Health Administration Pharmacology and Toxicology of Amphetamine and Related Designer Drugs Editors: Khursheed Asghar, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Errol De Souza, Ph.D. Addiction Research Center National Institute on Drug Abuse NIDA Research Monograph 94 1989 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 Pharmacology and Toxicology of Amphetamine and Related Designer Drugs ACKNOWLEDGMENT This monograph is based upon papers and discussion from a technical review on pharmacology and toxicology of amphetamine and related designer drugs that took place on August 2 through 4, 1988, in Bethesda, MD. The review meeting was sponsored by the Biomedical Branch, Division of Preclinical Research, and the Addiction Research Center, National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other matieral in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. -
Methamphetamine (Canadian Drug Summary)
www.ccsa.ca • www.ccdus.ca March 2020 Canadian Drug Summary Methamphetamine Key Points • The prevalence of methamphetamine use in the Canadian population is low (~0.2%). • Several jurisdictions report at least a three-fold increase in the use of methamphetamine over the past five years among individuals accessing treatment or harm reduction services. • Notable increases for rates of criminal violations involving methamphetamine have been observed in the last five years (2013–2018). Introduction Methamphetamine is a synthetic drug classified as a central nervous system (CNS) stimulant or psychostimulant. CNS stimulants cover a wide range of substances that act on the body by increasing the level of activity of the CNS and include caffeine, nicotine, amphetamine (e.g., Adderall®), methylphenidate (e.g., Ritalin®), MDMA (“ecstasy”), cocaine (including crack cocaine) and methamphetamine (including crystal meth).1,2 While both methamphetamine and amphetamine are psychostimulants and often grouped together, they are different drugs. A slight chemical modification of amphetamine produces methamphetamine, which has a different pharmacological profile that results in a larger release of certain neurochemicals in the brain and a stronger and more rapid physiological response. Some amphetamines are prescribed in Canada for attention-deficit hyperactivity disorder (ADHD) and narcolepsy (e.g., Adderall and Vyvanse®), but methamphetamine use is currently illegal. Methamphetamine is often made in illegal, clandestine laboratories with commonly available, inexpensive chemicals, such as ephedrine and pseudoephedrine, found in medications, among other sources. The use of these medications as precursor chemicals for methamphetamine led to stricter regulations introduced in Canada in 2006, limiting access to them by requiring they be kept behind the counter of pharmacies.3 Illegal production can be dangerous due to the toxicity of the chemicals used and the high risk of explosions. -
Toxicology Report Division of Toxicology Daniel D
Franklin County Forensic Science Center Office of the Coroner Anahi M. Ortiz, M.D. 2090 Frank Road Columbus, Ohio 43223 Toxicology Report Division of Toxicology Daniel D. Baker, Chief Toxicologist Casey Goodson Case # LAB-20-5315 Date report completed: January 28, 2021 A systematic toxicological analysis has been performed and the following agents were detected. Postmortem Blood: Gray Top Thoracic ELISA Screen Acetaminophen Not Detected ELISA Screen Barbiturates Not Detected ELISA Screen Benzodiazepines Not Detected ELISA Screen Benzoylecgonine Not Detected ELISA Screen Buprenorphine Not Detected ELISA Screen Cannabinoids See Confirmation ELISA Screen Fentanyl Not Detected ELISA Screen Methamphetamine Not Detected ELISA Screen Naltrexone/Naloxone Not Detected ELISA Screen Opiates Not Detected ELISA Screen Oxycodone/Oxymorphone Not Detected ELISA Screen Salicylates Not Detected ELISA Screen Tricyclics Not Detected Page 1 of 4 Casey Goodson Case # LAB-20-5315 GC/FID Ethanol Not Detected GC/MS Acidic/Neutral Drugs None Detected GC/MS Nicotine Positive GC/MS Cotinine Positive Reference Lab Delta-9-THC 13 ng/mL Reference Lab 11-Hydroxy-Delta-9-THC 1.2 ng/mL Reference Lab 11-Nor-9-Carboxy-Delta-9-THC 15 ng/mL Postmortem Urine: Gray Top Urine GC/MS Cotinine Positive This report has been verified as accurate and complete by ______________________________________ Daniel D. Baker, M.S., F-ABFT Cannabinoid quantitations in blood were performed by NMS Labs, Horsham, PA. Page 2 of 4 Casey Goodson Case # LAB-20-5315 Postmortem Toxicology Scope of Analysis Franklin County Coroner’s Office Division of Toxicology Enzyme Linked Immunosorbant Assay (ELISA) Blood Screen: Qualitative Presumptive Compounds/Classes: Acetaminophen (cut-off 10 µg/mL), Benzodiazepines (cut-off 20 ng/mL), Benzoylecgonine (cut-off 50 ng/mL), Cannabinoids (cut-off 40 ng/mL), Fentanyl (cut-off 1 ng/mL), Methamphetamine/MDMA (cut-off 50 ng/mL), Opiates (cut-off 40 ng/mL), Oxycodone/Oxymorphone (cut-off 40 ng/mL), Salicylates (50 µg/mL). -
Presented to the Graduate Council of the University of North Texas in Partial Fulfillment of the Requirements for the Degree Of
3-7? CHEMICAL IONIZATION (CI) GC/MS ANALYSIS OF UNDERIVATIZED AMPHETAMINES FOLLOWED BY CHIRAL DERIVATIZATION TO IDENTIFY d AND 1-ISOMERS WITH ION TRAP MASS SPECTROMETRY THESIS Presented to the Graduate Council of the University of North Texas in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE (Pharmacology) By John A. Tarver B.S.,B.A. May, 1991 Tarver, John A. Chemical Ionization (CI) GC/MS Analysis of Underivatized Amphetamines Followed by Chiral Derivatiza- tion to Identify d and 1-Isomers with Ion Trap Mass Spectro- metry. Master of Science (Biomedical Sciences), May, 1991, 26 pp., 9 figures, bibliography, 20 titles. An efficient two step procedure has been developed using CI GC/MS for analyzing amphetamines and related compounds. The first step allows the analysis of underiv- atized amphetamines with the necessary sensitivity and specificity to give spectral identification, including differentiation between methamphetamine and phentermine. The second step involves preparing a chiral derivative of the extract to identify d and 1-isomeric composition. TABLE OF CONTENTS Page LIST OF ILLUSTRATIONS.......... ... .. .. .......... iv INTRODUCTION .1........................... EXPERIMENTAL MATERIALS ...--- - - - - ----... -....-..... 15 METHODS --------------------.---...... 15 RESULTS AND DISCUSSION ...-..-..................... 17 CONCLUSION - - - - - -- - - - - --- - --- . - . 23 APPENDIX......... ---. -----....-.-. ----.. -........ 24 REFERENCES ----------------------------.. --. ...---.. 28 iii LIST OF ILLUSTRATIONS -
Phenylmorpholines and Analogues Thereof Phenylmorpholine Und Analoge Davon Phenylmorpholines Et Analogues De Celles-Ci
(19) TZZ __T (11) EP 2 571 858 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 265/30 (2006.01) A61K 31/5375 (2006.01) 20.06.2018 Bulletin 2018/25 A61P 25/24 (2006.01) A61P 25/16 (2006.01) A61P 25/18 (2006.01) (21) Application number: 11723158.9 (86) International application number: (22) Date of filing: 20.05.2011 PCT/US2011/037361 (87) International publication number: WO 2011/146850 (24.11.2011 Gazette 2011/47) (54) PHENYLMORPHOLINES AND ANALOGUES THEREOF PHENYLMORPHOLINE UND ANALOGE DAVON PHENYLMORPHOLINES ET ANALOGUES DE CELLES-CI (84) Designated Contracting States: • DECKER, Ann Marie AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Durham, North Carolina 27713 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (74) Representative: Hoeger, Stellrecht & Partner Patentanwälte mbB (30) Priority: 21.05.2010 US 347259 P Uhlandstrasse 14c 70182 Stuttgart (DE) (43) Date of publication of application: 27.03.2013 Bulletin 2013/13 (56) References cited: WO-A1-2004/052372 WO-A1-2008/026046 (73) Proprietors: WO-A1-2008/087512 DE-B- 1 135 464 • Research Triangle Institute FR-A- 1 397 563 GB-A- 883 220 Research Triangle Park, North Carolina 27709 GB-A- 899 386 US-A1- 2005 267 096 (US) • United States of America, as represented by • R.A. GLENNON ET AL.: "Beta-Oxygenated The Secretary, Department of Health and Human Analogues of the 5-HT2A Serotonin Receptor Services Agonist Bethesda, Maryland 20892-7660 (US) 1-(4-Bromo-2,5-dimethoxyphenyl)-2-aminopro pane", JOURNAL OF MEDICINAL CHEMISTRY, (72) Inventors: vol. -
Conversion Factors Psychotropics
Green List 30th edition, 2019 Annex to the annual statistical report on International Narcotics Control Board psychotropic substances (form P) List of Psychotropic Substances under International Control In accordance with the Convention on Psychotropic Substances of 1971 UPDATES • Inclusion of 5 new substances in Schedule II : ADB-CHMINACA, ADB-FUBINACA, CUMYL- 4CN-BINACA, N-ETHYLNORPENTYLONE and FUB-AMB. The Green List has been prepared by the International Narcotics Control Board to assist Governments in completing the annual statistical report on psychotropic substances (form P) and the quarterly statistics of imports and exports of substances in Schedule II of the Convention on Psychotropic Substances of 1971 (form A/P). For information on the names used for substances under international control and preparations containing such substances, as well as on chemical and structural formulae and other techni cal information, see Multilingual Dictionary of Narcotic Drugs and Psychotropic Substances under International Control .1 __________________ 1 United Nations publication, Sales No. M.06.XI.16. V.19-08673 (E) *1908673* The Green List is divided into three parts: Part one. Substances in Schedules I, II, III and IV of the Convention on Psychotropic Substances of 1971; Part two. Pure drug content of bases and salts of psychotropic substances under international control; Part three. Prohibition of and restrictions on export and import pursuant to article 13 of the Convention on Psychotropic Substances of 1971. 2 Part one. Substances in Schedules I, II, III and IV of the Convention on Psychotropic Substances of 1971 Psychotropic substances under international control are presented in the schedules below. Where an international non-proprietary name (INN) is available for a substance, that INN is given in the left -hand column. -
Recommended Methods for the Identification and Analysis Of
Vienna International Centre, P.O. Box 500, 1400 Vienna, Austria Tel: (+43-1) 26060-0, Fax: (+43-1) 26060-5866, www.unodc.org RECOMMENDED METHODS FOR THE IDENTIFICATION AND ANALYSIS OF AMPHETAMINE, METHAMPHETAMINE AND THEIR RING-SUBSTITUTED ANALOGUES IN SEIZED MATERIALS (revised and updated) MANUAL FOR USE BY NATIONAL DRUG TESTING LABORATORIES Laboratory and Scientific Section United Nations Office on Drugs and Crime Vienna RECOMMENDED METHODS FOR THE IDENTIFICATION AND ANALYSIS OF AMPHETAMINE, METHAMPHETAMINE AND THEIR RING-SUBSTITUTED ANALOGUES IN SEIZED MATERIALS (revised and updated) MANUAL FOR USE BY NATIONAL DRUG TESTING LABORATORIES UNITED NATIONS New York, 2006 Note Mention of company names and commercial products does not imply the endorse- ment of the United Nations. This publication has not been formally edited. ST/NAR/34 UNITED NATIONS PUBLICATION Sales No. E.06.XI.1 ISBN 92-1-148208-9 Acknowledgements UNODC’s Laboratory and Scientific Section wishes to express its thanks to the experts who participated in the Consultative Meeting on “The Review of Methods for the Identification and Analysis of Amphetamine-type Stimulants (ATS) and Their Ring-substituted Analogues in Seized Material” for their contribution to the contents of this manual. Ms. Rosa Alis Rodríguez, Laboratorio de Drogas y Sanidad de Baleares, Palma de Mallorca, Spain Dr. Hans Bergkvist, SKL—National Laboratory of Forensic Science, Linköping, Sweden Ms. Warank Boonchuay, Division of Narcotics Analysis, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Dr. Rainer Dahlenburg, Bundeskriminalamt/KT34, Wiesbaden, Germany Mr. Adrian V. Kemmenoe, The Forensic Science Service, Birmingham Laboratory, Birmingham, United Kingdom Dr. Tohru Kishi, National Research Institute of Police Science, Chiba, Japan Dr. -
Doping Control of Athletes
trends in analytical chemistry, vol. 7, no. IO, I988 375 trends Doping control of athletes E. G. de Jong*, I?. A. A. Maes and The definition of the Council of Europe for doping J. M. van Rossum is2: Utrecht, Netherlands ‘The administration to or the use by a healthy indi- vidual in any way of compounds which are not natu- History ral to the organism or the use of physiological com- The origin of the word doping is not certain. It first pounds in abnormal doses or in an abnormal way appeared in the English dictionaries at the end of the with the only purpose to artificially and dishonestly nineteenth century. The first reference to the use of influence the performance of this person during doping by athletes was in 1864 during swimming competition.’ competitions that were held in the canals of Amster- Another possible definition is: dam. The use of what is known as a ‘speedball’, a ‘The use of compounds which are not synthesized mixture of heroine and cocaine, by cyclists was de- by the human body or the use of endogenous com- scribed in 1869. In 1904 the Russian chemist pounds in excessive doses with the aim to improve Bukowski was able to identify some alkaloids in the performance in sport competitions.’ saliva of horses’. A simpler definition is: Australia was the first country to take measures ‘The use of forbidden drugs. ’ against doping in sports in 1962, and England fol- The last definition can only be used when we have lowed with the drugs bill in 1964.