DOCSLIB.ORG

Cannabinoids, Stimulants, and Hallucinogens

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cannabinoids, Stimulants, and Hallucinogens Chapter 88 Novel Drugs of Abuse: Cannabinoids, Stimulants, and Hallucinogens Evan S. Herrmann, Patrick S. Johnson, Matthew W. Johnson, Ryan Vandrey Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abbreviations pFPP para-Fluorophenylpiperazine SCBs Synthetic cannabinoids 25B-NBOMe 2-(4-Bromo-2,5-dimethoxyphenyl)-N-[(2-methoxy- TFMPP 3-Trifluoromethylphenylpiperazine phenyl)methyl]ethanamine THC Δ9-Tetrahydrocannabinol 25C-NBOMe 2-(4-Chloro-2,5-dimethoxyphenyl)-N-[(2-methoxy- α-PVP alpha-Pyrrolidinovalerophenone phenyl)methyl]ethanamine 25I-NBOMe 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl) INTRODUCTION methyl]ethanamine 2C-B 4-Bromo-2,5-dimethoxyphenethylamine From 2009 to 2012, 164 unique and previously undetected 2C-B-BZP 4-Bromo-2,5-dimethoxy-1-benzylpiperazine psychoactive compounds were observed following analyses 2C-E 2,5-Dimethoxy-4-ethylphenethylamine of illicit drugs confiscated and tested in Europe (European 2C-I 2,5-Dimethoxy-4-iodophenethylamine Monitoring Centre for Drugs and Drug Addiction, 2012). This 2C-T-7 2,5-Dimethoxy-4-propylthiophenethylamine trend is a sharp contrast to most of the 20th century, when a 4-AcO-DMT O-Acetylpsilocin comparatively small number of psychoactive recreational 4-MEC 4-Methyl-N-ethylcathinone drugs were available on illicit drug markets. Although many 4-MePPP 4-Methyl-α-pyrrolidinopropiophenone new compounds continue to be identified annually, most of 5-HT 5-Hydroxytryptamine those that have emerged as popular drugs of abuse since the 5-MeO-AMT 5-Methoxy-α-methyltryptamine late 1990s can generally be classified into one of six categories 5-MeO-DALT N,N-Diallyl-5-methoxytryptamine based on similarities in both molecular structure and in 5-MeO-DiPT 5-Methoxy-diisopropyltryptamine physiological, subjective, and behavioral effects: synthetic Bromo-DragonFLY 1-(4-Bromofuro[2,3-f][1]benzofuran-8-yl)- cannabinoids (SCBs); synthetic cathinones; phenethylamines; propan-2-amine piperazines; tryptamines; and Salvia divinorum. Some of these BZP Benzylpiperazine compounds (e.g., newer “second-generation” synthetic cathi- CB1 Cannabinoid receptor type 1 nones) were first synthesized shortly before they emerged as CB2 Cannabinoid receptor type 2 recreational drugs, while others (e.g., S. divinorum) have had DMT N,N-Dimethyltryptamine known psychoactive properties for hundreds of years, but have DOB 2,5-Dimethoxy-4-bromoamphetamine just recently become popular as drugs of abuse. DOC 2,5-Dimethoxy-4-chloroamphetamine This chapter focuses on providing a review of the basic DOI 2,5-Dimethoxy-4-iodoamphetamine pharmacology, history, current trends of use, and psychological, DOM 2,5-Dimethoxy-4-methylamphetamine subjective, and behavioral effects of representative substances DSM-IV Diagnostic and Statistical Manual for Metal Disorders, in each of the aforementioned drug classes. Because this is a 4th Edition relatively new and rapidly emerging area of study on an unstable DEA Drug Enforcement Administration drug market, the inclusiveness of drugs and related scientific LSD Lysergic acid diethylamide data described in this chapter are somewhat limited. However, MDMA 3,4-Methylenedioxy-methamphetamine the data available are sufficient to provide a general overview MDPV 3,4-Methylenedioxypyrovalerone of these novel classes of substances, supplemented by providing MeOPP para-Methoxyphenylpiperazine examples of specific compounds that are representative of each Mephedrone 4-Methylmethcathinone drug class. When possible, we provide references to published Methylone 3,4-Methylenedioxymethcathinone work that provides more in-depth information on individual Naphyrone Naphthylpyrovalerone compounds. Neuropathology of Drug Addictions and Substance Misuse, Volume 3. 893 894 PART | VII Emerging Addictions and Drugs of Abuse SYNTHETIC CANNABINOIDS these substances via regulatory mechanisms typically used for con- trolling drugs of abuse. However, clandestine chemists’ response As a broad classification, SCBs can include any synthetically to this was to drastically increase the number of compounds, with derived compounds that have a binding affinity for and pharmaco- similar pharmacology, but distinct chemical structures, used to adul- logically modulate (e.g., have agonist, antagonist, inverse agonist, terate the plant material in commercially available SCB products neutral antagonist effects) endogenous cannabinoid receptors (e.g., (Seely et al., 2013). Indeed, the number of new SCBs on the illicit cannabinoid receptor types 1 and 2; CB1 and CB2). The develop- drug market increased rapidly from two new compounds in 2009 to ment of SCBs began when the structure and function of the CB1 51 new compounds in 2012 (Randolph, 2014). Hundreds of brands receptor was discovered and characterized in the late 1980s (e.g., emerged and the availability and use of these products increased Devane, Dysarz, Johnson, Melvin, & Howlett, 1988). Following rapidly from 2009 to 2011 as media reports and Internet content the discovery of the endogenous cannabinoid receptor system, a expanded awareness of their existence and availability. number of SCBs were formulated and evaluated by academic sci- Due to the relatively recent availability of SCBs on the drug entists as pharmacologic tools for understanding endocannabinoid market, few data are available on SCB use from large represen- pharmacology and neurobiology, or by pharmaceutical companies tative drug use surveys. Perhaps the best available epidemiologi- as candidate medications for the treatment of various health condi- cal data is from the US Monitoring the Future survey. Outcomes tions (Gurney, Scott, Kacinko, Presley, & Logan, 2014). from that study suggest that the prevalence of SCB use peaked Beginning around the year 2004, retail products sold primar- among US high-school seniors (grade 12) in 2011, when 11.4% ily under the brand name “Spice” began to surface in Europe of students surveyed indicated that they had used an SCB product (Psychonaut Web Mapping Research Group, 2009). Spice products in the past year (Johnston, O’Malley, Bachman, Schulenberg, & consisted of inert dried plant material that later was discovered to Miech, 2014). Data from more recent Monitoring the Future sur- have been adulterated with one or more SCBs (Auwärter et al., veys suggest the prevalence of use among surveyed students has 2009). The general consensus is that chemists in clandestine declined annually, with past year use being reported by only 6% in laboratories were mining the published work of scientists such as 2014 (Johnston et al., 2014). More detailed analyses of Monitor- John Huffman and Alex Makriyannis to find potent CB1 receptor ing the Future survey data indicated that use of alcohol, tobacco, agonists that were not explicitly regulated chemicals under drug or other drugs was robustly associated with increased odds of SCB laws at the time (Table 1 displays common synthetic cannabinoid use, with intensity of use of natural cannabis being the most robust products grouped according to scientific origin). These products predictor of SCB use (e.g., only 0.5% of those who had never used were, and continue to be, sold as “herbal blends,” “incense,” or cannabis reported use of SCBs in the past year, whereas 39.8% of “potpourri” in retail stores (e.g., tobacco shops, “head” shops, gas those who had used cannabis 40 or more times in their lifetime stations) or from Internet-based vendors and labeled as “not for reported SCB use in the past year) (Palamar & Acosta, 2015). human consumption.” This type of labeling is used by distributors Another proxy for the prevalence of use is data tracking by as a means of selling psychoactive substances without overtly vio- emergency health providers. In the United States, calls to poison lating drug control laws, though the legality of this remains a point control centers reported only 13 cases related to SCB administra- of contention (e.g., Vandrey, Dunn, Fry, & Girling, 2012). tion in 2009. The number of SCB-associated cases then increased Forensic analysis of products began in earnest to identify and annually from 2906 in 2010 to a peak of 6959 calls in 2011. SCB- characterize the SCBs used in Spice and similar products. Initial test- related calls to poison control centers declined in 2012 and 2013 ing identified JWH-018, JWH-073, JWH-250, JWH-398, HU-210, (5200 and 2668, respectively), but increased again in 2014 to a and CP-47,497 as the predominant compounds used. This resulted total of 3680 in 2014 (American Association of Poison Control in relatively fast action by governing authorities to effectively ban Centers, 2015). Controlled studies evaluating the effects of SCBs have been rare and limited to preclinical experiments. These studies indicate that the SCBs commonly found in commercial products intended TABLE 1 Synthetic Cannabinoids for illicit drug use typically have the following characteristics: (1) Specific Compounds they have high affinity for the CB1 receptor; (2) they are full ago- Commonly Found in nists at the CB1 receptor; (3) they are highly potent; (4) they share Origin (First Synthetic Cannabis discriminative stimulus properties with Δ9-tetrahydrocannabinol Family Synthesized) Products (THC), the primary psychoactive compound in cannabis; and (5) the potent psychoactive metabolites have been observed for some CP Pfizer CP 47,497 compounds (e.g., Fantegrossi, Moran, Radominska-Pandya, & HU Raphael Mechoulam, HU-210
Load more

Recommended publications
  • Adverse Reactions to Hallucinogenic Drugs. 1Rnstttutton National Test
    DOCUMENT RESUME ED 034 696 SE 007 743 AUTROP Meyer, Roger E. , Fd. TITLE Adverse Reactions to Hallucinogenic Drugs. 1rNSTTTUTTON National Test. of Mental Health (DHEW), Bethesda, Md. PUB DATP Sep 67 NOTE 118p.; Conference held at the National Institute of Mental Health, Chevy Chase, Maryland, September 29, 1967 AVATLABLE FROM Superintendent of Documents, Government Printing Office, Washington, D. C. 20402 ($1.25). FDPS PRICE FDPS Price MFc0.50 HC Not Available from EDRS. DESCPTPTOPS Conference Reports, *Drug Abuse, Health Education, *Lysergic Acid Diethylamide, *Medical Research, *Mental Health IDENTIFIEPS Hallucinogenic Drugs ABSTPACT This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different methods of therapy. Data are also presented on the psychological and physiolcgical effects of L.S.D. given as a treatment under controlled medical conditions. Possible genetic effects of L.S.D. and other drugs are discussed on the basis of data from laboratory animals and humans. Also discussed are needs for futher research. The necessity to aviod scare techniques in disseminating information about drugs is emphasized. An aprentlix includes seven background papers reprinted from professional journals, and a bibliography of current articles on the possible genetic effects of drugs. (EB) National Clearinghouse for Mental Health Information VA-w. Alb alb !bAm I.S. MOMS Of NAM MON tMAN IONE Of NMI 105 NUNN NU IN WINES UAWAS RCM NIN 01 NUN N ONMININI 01011110 0.
    [Show full text]
  • Neuroreceptor Activation by Vibration-Assisted Tunneling
    OPEN Neuroreceptor Activation by SUBJECT AREAS: Vibration-Assisted Tunneling BIOPHYSICAL CHEMISTRY Ross D. Hoehn1, David Nichols2, Hartmut Neven3 & Sabre Kais4,5,6 MECHANISM OF ACTION 1Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA, 2Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA,3 Google, Venice, CA 90291, USA,4 Department of Received 5 20 October 2014 Chemistry, Purdue University, West Lafayette, IN 47907, USA, Departments of Physics, Purdue University, West Lafayette, IN 47907, USA,6 Qatar Environment and Energy Research Institute, Qatar Foundation, Doha, Qatar. Accepted 20 March 2015 G protein-coupled receptors (GPCRs) constitute a large family of receptor proteins that sense molecular Published signals on the exterior of a cell and activate signal transduction pathways within the cell. Modeling how an 24 April 2015 agonist activates such a receptor is fundamental for an understanding of a wide variety of physiological processes and it is of tremendous value for pharmacology and drug design. Inelastic electron tunneling spectroscopy (IETS) has been proposed as a model for the mechanism by which olfactory GPCRs are activated by a bound agonist. We apply this hyothesis to GPCRs within the mammalian nervous system Correspondence and using quantum chemical modeling. We found that non-endogenous agonists of the serotonin receptor share requests for materials a particular IET spectral aspect both amongst each other and with the serotonin molecule: a peak whose should be addressed to intensity scales with the known agonist potencies. We propose an experiential validation of this model by S.K. (kais@purdue. utilizing lysergic acid dimethylamide (DAM-57), an ergot derivative, and its deuterated isotopologues; we also provide theoretical predictions for comparison to experiment.
    [Show full text]
  • DEMAND REDUCTION a Glossary of Terms
    UNITED NATIONS PUBLICATION Sales No. E.00.XI.9 ISBN: 92-1-148129-5 ACKNOWLEDGEMENTS This document was prepared by the: United Nations International Drug Control Programme (UNDCP), Vienna, Austria, in consultation with the Commonwealth of Health and Aged Care, Australia, and the informal international reference group. ii Contents Page Foreword . xi Demand reduction: A glossary of terms . 1 Abstinence . 1 Abuse . 1 Abuse liability . 2 Action research . 2 Addiction, addict . 2 Administration (method of) . 3 Adverse drug reaction . 4 Advice services . 4 Advocacy . 4 Agonist . 4 AIDS . 5 Al-Anon . 5 Alcohol . 5 Alcoholics Anonymous (AA) . 6 Alternatives to drug use . 6 Amfetamine . 6 Amotivational syndrome . 6 Amphetamine . 6 Amyl nitrate . 8 Analgesic . 8 iii Page Antagonist . 8 Anti-anxiety drug . 8 Antidepressant . 8 Backloading . 9 Bad trip . 9 Barbiturate . 9 Benzodiazepine . 10 Blood-borne virus . 10 Brief intervention . 11 Buprenorphine . 11 Caffeine . 12 Cannabis . 12 Chasing . 13 Cocaine . 13 Coca leaves . 14 Coca paste . 14 Cold turkey . 14 Community empowerment . 15 Co-morbidity . 15 Comprehensive Multidisciplinary Outline of Future Activities in Drug Abuse Control (CMO) . 15 Controlled substance . 15 Counselling and psychotherapy . 16 Court diversion . 16 Crash . 16 Cross-dependence . 17 Cross-tolerance . 17 Custody diversion . 17 Dance drug . 18 Decriminalization or depenalization . 18 Demand . 18 iv Page Demand reduction . 19 Dependence, dependence syndrome . 19 Dependence liability . 20 Depressant . 20 Designer drug . 20 Detoxification . 20 Diacetylmorphine/Diamorphine . 21 Diuretic . 21 Drug . 21 Drug abuse . 22 Drug abuse-related harm . 22 Drug abuse-related problem . 22 Drug policy . 23 Drug seeking . 23 Drug substitution . 23 Drug testing . 24 Drug use .
    [Show full text]
  • Molecular Mechanisms of Addiction
    Molecular Mechanisms of Addiction Eric J. Nestler Nash Family Professor The Friedman Brain Institute Medical Model of Addiction • Pathophysiology - To identify changes that drugs produce in a vulnerable brain to cause addiction. • Individual Risk - To identify specific genes and non-genetic factors that determine an individual’s risk for (or resistance to) addiction. - About 50% of the risk for addiction is genetic. Only through an improved understanding of the biology of addiction will it be possible to develop better treatments and eventually cures and preventive measures. Scope of Drug Addiction • 25% of the U.S. population has a diagnosis of drug abuse or addiction. • 50% of U.S. high school graduates have tried an illegal drug; use of alcohol and tobacco is more common. • >$400 billion incurred annually in the U.S. by addiction: - Loss of life and productivity - Medical consequences (e.g., AIDS, lung cancer, cirrhosis) - Crime and law enforcement Diverse Chemical Substances Cause Addiction • Opiates (morphine, heroin, oxycontin, vicodin) • Cocaine • Amphetamine and like drugs (methamphetamine, methylphenidate) • MDMA (ecstasy) • PCP (phencyclidine or angel dust; also ketamine) • Marijuana (cannabinoids) • Tobacco (nicotine) • Alcohol (ethanol) • Sedative/hypnotics (barbiturates, benzodiazepines) Chemical Structures of Some Drugs of Abuse Cocaine Morphine Ethanol Nicotine ∆9-tetrahydrocannabinol Drugs of Abuse Use of % of US population as weekly users 100 25 50 75 0 Definition of Drug Addiction • Loss of control over drug use. • Compulsive drug seeking and drug taking despite horrendous adverse consequences. • Increased risk for relapse despite years of abstinence. Definition of Drug Addiction • Tolerance – reduced drug effect after repeated use. • Sensitization – increased drug effect after repeated use.
    [Show full text]
  • Use of Sympathomimetic Drugs Leads to Increased Risk of Hospitalization for Arrhythmias in Patients with Congestive Heart Failure
    ORIGINAL INVESTIGATION Use of Sympathomimetic Drugs Leads to Increased Risk of Hospitalization for Arrhythmias in Patients With Congestive Heart Failure Marcel L. Bouvy, PharmD; Eibert R. Heerdink, PhD; Marie L. De Bruin, PharmD; Ron M. C. Herings, PhD; Hubert G. M. Leufkens, PhD; Arno W. Hoes, PhD Background: Sympathomimetic agents have a direct exposure to sympathomimetic agents, expressed as positive chronotropic effect on heart rate and may cause odds ratios. hypokalemia, even when administered by inhalation. In selected patients (eg, patients with congestive heart fail- Results: Of 149 case patients, a total of 33 (22.1%) were ure [CHF]) this can lead to arrhythmias. Despite the po- treated with any sympathomimetic agent, and 6 pa- tential adverse effects of these agents, they are used fre- tients (4.0%) were treated with systemic sympathomi- quently in patients with CHF, due to a high incidence of metics. The use of any sympathomimetic drug was as- respiratory comorbidity. This study investigates the ef- sociated with an increased risk of admission for arrhythmia fects of sympathomimetics on the incidence of hospital- (odds ratio, 4.0; 95% confidence interval, 1.0-15.1). For izations for arrhythmias in patients with CHF. systemic sympathomimetic drugs, the corresponding odds ratio was 15.7 (95% confidence interval, 1.1-228.0). Methods: In a cohort of 1208 patients with a validated hospital discharge diagnosis of CHF, we identified 149 Conclusions: The results of this study strongly suggest cases with a readmission for arrhythmias, and com- an increased risk of hospitalization for arrhythmias in pa- pared these in a nested matched case-control design tients with CHF treated with sympathomimetic drugs.
    [Show full text]
  • Adrenergic Drugs
    Adrenergic Drugs Overview Overview -- Adrenergic drugs exert their principal pharmacological and • therapeutic effects by either enhancing or reducing the activity of the sympathetic division of the autonomic nervous system. Substances (drugs)that produce effects similar to stimulation of sympathetic nervous activity are known as sympathomimetics or adrenergic stimulants. Those that decrease sympathetic activity are referred to as sympatholyti- cs, antiadrenergics, or adrenergic-blocking agents. Overview -- Adrenergic agents either act on adrenergic • receptors (adrenoceptors, ARs) or affect the life cycle of adrenergic neurotransmitters (NTs), including norepinephrine (NE, noradrenaline), epinephrine (E, adrenaline), and dopamine (DA). Normally these NTs modulate many vital functions, such as the rate and force of cardiac contraction, constriction and dilation of blood vessels and bronchioles, the release of insulin, and the breakdown of fat (table 16.1). Overview Adrenergic NTs(structure and physicochemical properties) -- NE, E, and DA are chemically catecholamines (CAs), which • refer generally to all organic compounds that contain a catechol nucleus (ortho-dihydroxybenzene) and an ethylamine group • (Fig. 16.1). In a physiological context, the term usually means DA and its metabolites NE and E. E contains one secondary amino group and three hydroxyl groups. Using calculated log p(-0.63) of E, one would expect the molecule is polar and soluble in water. NTs NTs -- E is a weak base (pKa = 9.9) because of its aliphatic • amino group. It is also a weak acid (pKa =8.7) because of its phenolic hydroxyl groups. It can be predicted that ionized species (the cation form) of E at physiological pH is predominant (log D at pH 7 = -2.75).
    [Show full text]
  • GPCR/G Protein
    Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com GPCR/G Protein G Protein Coupled Receptors (GPCRs) perceive many extracellular signals and transduce them to heterotrimeric G proteins, which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signaling pathways. G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). In unstimulated cells, the state of G alpha is defined by its interaction with GDP, G beta-gamma, and a GPCR. Upon receptor stimulation by a ligand, G alpha dissociates from the receptor and G beta-gamma, and GTP is exchanged for the bound GDP, which leads to G alpha activation. G alpha then goes on to activate other molecules in the cell. These effects include activating the MAPK and PI3K pathways, as well as inhibition of the Na+/H+ exchanger in the plasma membrane, and the lowering of intracellular Ca2+ levels. Most human GPCRs can be grouped into five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin, forming the GRAFS classification system. A series of studies showed that aberrant GPCR Signaling including those for GPCR-PCa, PSGR2, CaSR, GPR30, and GPR39 are associated with tumorigenesis or metastasis, thus interfering with these receptors and their downstream targets might provide an opportunity for the development of new strategies for cancer diagnosis, prevention and treatment. At present, modulators of GPCRs form a key area for the pharmaceutical industry, representing approximately 27% of all FDA-approved drugs. References: [1] Moreira IS. Biochim Biophys Acta. 2014 Jan;1840(1):16-33.
    [Show full text]
  • Idiopathic Orthostatic Hypotension from Failure of Noradrenaline Release in a Patient with Vasomotor Innervation
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.1.11 on 1 January 1977. Downloaded from Journal ofNeurology, Neurosurgery, and Psychiatry, 1977, 40, 11-19 Idiopathic orthostatic hypotension from failure of noradrenaline release in a patient with vasomotor innervation R. N. NANDA,1 F. C. BOYLE, J. S. GILLESPIE, R. H. JOHNSON,2 AND H. J. KEOGH From the University Department ofNeurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, and the University Department ofPharmacology, Glasgow SUMMARY A 26 year old man is described with life-long orthostatic hypotension unrelated to autonomic nerve degeneration and apparently due to failure ofperipheral noradrenaline release. Tests of parasympathetic and sympathetic cholinergic nerve function were normal, but sympathetic adren- ergic activity was defective. Thus blood pressure regulation was abnormal. There was no pressor response to tyramine, an indirect sympathomimetic drug, but a marked pressor response to the directly acting sympathomimetic drugs phenylephrine and noradrenaline. On standing there was a guest. Protected by copyright. progressive fall rather than a rise in circulating noradrenaline concentrations, although adrenaline levels rose normally. The pupils showed diminished responses to ephedrine and cocaine, and a normal response to phenylephrine. Fluorescence microscopy of blood vessels showed that they were in- nervated with adrenergic nerves. His orthostatic hypotension responded well to oral phenylephrine (50 mg five times daily) but not to other forms of therapy. It is suggested that this patient's symptoms were due to failure of noradrenaline release even though sympathetic adrenergic nerves were present. We therefore wish to draw attention to a further cause oforthostatic hypotension, failure ofperipheral noradrenaline release without autonomic neuropathy.
    [Show full text]
  • Vol. 85 Tuesday, No. 67 April 7, 2020 Pages 19375–19640
    Vol. 85 Tuesday, No. 67 April 7, 2020 Pages 19375–19640 OFFICE OF THE FEDERAL REGISTER VerDate Sep 11 2014 21:02 Apr 06, 2020 Jkt 250001 PO 00000 Frm 00001 Fmt 4710 Sfmt 4710 E:\FR\FM\07APWS.LOC 07APWS khammond on DSKJM1Z7X2PROD with FR-1WS II Federal Register / Vol. 85, No. 67 / Tuesday, April 7, 2020 The FEDERAL REGISTER (ISSN 0097–6326) is published daily, SUBSCRIPTIONS AND COPIES Monday through Friday, except official holidays, by the Office PUBLIC of the Federal Register, National Archives and Records Administration, under the Federal Register Act (44 U.S.C. Ch. 15) Subscriptions: and the regulations of the Administrative Committee of the Federal Paper or fiche 202–512–1800 Register (1 CFR Ch. I). The Superintendent of Documents, U.S. Assistance with public subscriptions 202–512–1806 Government Publishing Office, is the exclusive distributor of the official edition. Periodicals postage is paid at Washington, DC. General online information 202–512–1530; 1–888–293–6498 Single copies/back copies: The FEDERAL REGISTER provides a uniform system for making available to the public regulations and legal notices issued by Paper or fiche 202–512–1800 Federal agencies. These include Presidential proclamations and Assistance with public single copies 1–866–512–1800 Executive Orders, Federal agency documents having general (Toll-Free) applicability and legal effect, documents required to be published FEDERAL AGENCIES by act of Congress, and other Federal agency documents of public Subscriptions: interest. Assistance with Federal agency subscriptions: Documents are on file for public inspection in the Office of the Federal Register the day before they are published, unless the Email [email protected] issuing agency requests earlier filing.
    [Show full text]
  • 4-Fluoroamphetamine (4-FA) Critical Review Report Agenda Item 4.3
    4-Fluoroamphetamine (4-FA) Critical Review Report Agenda Item 4.3 Expert Committee on Drug Dependence Thirty-ninth Meeting Geneva, 6-10 November 2017 39th ECDD (2017) Agenda item 4.3 4-FA Contents Acknowledgements.................................................................................................................................. 4 Summary...................................................................................................................................................... 5 1. Substance identification ....................................................................................................................... 6 A. International Nonproprietary Name (INN).......................................................................................................... 6 B. Chemical Abstract Service (CAS) Registry Number .......................................................................................... 6 C. Other Chemical Names ................................................................................................................................................... 6 D. Trade Names ....................................................................................................................................................................... 6 E. Street Names ....................................................................................................................................................................... 6 F. Physical Appearance ......................................................................................................................................................
    [Show full text]
  • Journal of Pharmacology and Toxicological Studies
    e-ISSN:2322-0139 p-ISSN:2322-0120 RESEARCH AND REVIEWS: JOURNAL OF PHARMACOLOGY AND TOXICOLOGICAL STUDIES Exploration of Mechanism of Action of Ephedrine on Rat Blood Pressure. Paresh Solanki1, Preeti Praveen Yadav2*, Naresh D Kantharia2. 1Lambda Therapeutic Research LTD, Ahmedabad, Gujarat, India. 2Department of Pharmacology, Government Medical College, Surat, Gujarat, India. Research Article Received: 19/05/2014 ABSTRACT Revised: 20/06/2014 Accepted: 24/06/2014 The aim of the study is to study mechanism of action (direct, indirect or mixed) of ephedrine on rat blood pressure by *For Correspondence using agents affecting synthesis, storage and release of noradrenaline. 30 male Wistar albino rats divided into 6 groups Department of Pharmacology, (n=5). A: ephedrine control, B: tyramine control, C: reserpine + Government Medical College, metyrosine + ephedrine, D: reserpine + metyrosine + tyramine, E: Surat, Gujarat, India. desipramine + ephedrine, F: desipramine + tyramine. In A and B: Mobile: +91 9408670190 blood pressure responses of ephedrine and tyramine were taken for control, C and D: reserpine was injected 18 hrs. before and Keywords: Reserpine, metyrosine was injected 2 hrs before taking responses of ephedrine Metyrosine, Tyramine, or tyramine respectively. For E and F: desipramine w a s given 10 desipramine min. before taking response of ephedrine or tyramine respectively. Rat mean blood pressure was measured by using student’s physiograph. Reserpine and metyrosine, inhibits the vesicular uptake and synthesis of noradrenaline respectively decrease the pressor responses of tyramine significantly (p=0.000) but not of ephedrine (p=0.893).Prior administration of desipramine which inhibits axonal uptake of noradrenaline also significantly decreases the effect of tyramine (p=0.000) but do not affect the effect of ephedrine significantly (p=0.893).Study concludes the pressor effect of ephedrine is not mediated by release of noradrenaline from neurons, indicating that ephedrine act directly on adrenergic receptors.
    [Show full text]
  • Fluticasone Furoate; Umeclidinium Bromide; Vilanterol Trifenatate May 2021
    Contains Nonbinding Recommendations Draft – Not for Implementation Draft Guidance on Fluticasone Furoate; Umeclidinium Bromide; Vilanterol Trifenatate May 2021 This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the Office of Generic Drugs. This guidance, which interprets the Agency’s regulations on bioequivalence at 21 CFR part 320, provides product-specific recommendations on, among other things, the design of bioequivalence studies to support abbreviated new drug applications (ANDAs) for the referenced drug product. FDA is publishing this guidance to further facilitate generic drug product availability and to assist the generic pharmaceutical industry with identifying the most appropriate methodology for developing drugs and generating evidence needed to support ANDA approval for generic versions of this product. The contents of this document do not have the force and effect of law and are not meant to bind the public in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA guidances means that something is suggested or recommended, but not required. This is a new draft product-specific guidance for industry on generic fluticasone furoate; umeclidinium bromide; vilanterol trifenatate.
    [Show full text]