DOCSLIB.ORG

1 the ROLE of SERTONIN and VESICULAR MONOAMINE TRANSPORTERS in the ADVERSE RESPONSES to METHYLENEDIOXYMETHAMPHETAMINE by Lucina

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
1 the ROLE of SERTONIN and VESICULAR MONOAMINE TRANSPORTERS in the ADVERSE RESPONSES to METHYLENEDIOXYMETHAMPHETAMINE by Lucina The Role Of Sertonin And Vesicular Monoamine Transporters In The Adverse Responses To Methylenedioxymethamphetamine Item Type text; Electronic Dissertation Authors Lizarraga-Zazueta, Lucina Eridna Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 24/09/2021 17:03:12 Link to Item http://hdl.handle.net/10150/332686 1 THE ROLE OF SERTONIN AND VESICULAR MONOAMINE TRANSPORTERS IN THE ADVERSE RESPONSES TO METHYLENEDIOXYMETHAMPHETAMINE by Lucina Eridna Lizarraga Zazueta A Dissertation Submitted to the Faculty of the DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College at THE UNIVERSITY OF ARIZONA 2014 2 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by Lucina Eridna Lizarraga Zazueta entitled “The Role of Serotonin and Vesicular Monoamine Transporters in the Adverse Responses to Methylenedioxymethamphetamine” and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy ________________________________________________________________Date: 06/20/2014 Dr. Terrence J. Monks ________________________________________________________________Date: 06/20/2014 Dr. Serrine S. Lau ________________________________________________________________Date: 06/20/2014 Dr. John W. Regan _______________________________________________________________Date: 06/20/2014 Dr. Josephine Lai ________________________________________________________________Date: 06/20/2014 Dr. Stephen Wright Final approval and acceptance of this dissertation is contingent upon the candidate’s submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fulfilling the dissertation requirement. ________________________________________________ Date: 06/20/2014 Dissertation Director: Dr. Terrence J. Monks 3 STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this dissertation are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author. SIGNED: Lucina Eridna Lizarraga Zazueta 4 ACKNOWLEDGEMENTS I would like to begin by thanking the College of Pharmacy at the University of Arizona for giving me the opportunity to attain my goal of pursuing a graduate degree. Also, special thanks to my committee members, Dr. Serrine Lau, Dr. Josephine Lai, Dr. John Regan and Dr. Stephen Wright, for all their time and advice. In particular, I have to acknowledge my advisor, Dr. Terrence Monks, for his support and mentorship. His guidance was instrumental in helping me become the critical and independent scientist I am today. I have to express my most sincere gratitude to all my family, especially to my parents, Roberto and Maria, and brothers, Roberto, Pablo and Juan. Words cannot describe the love and admiration I have for all of you. You have been and will continue to be my source of strength and inspiration. Thank you to my husband and best friend, Ricardo, for all his love and support. You encourage me every day to pursuit my dreams and face my challenges, helping me to become a better person. I am very thankful for all the joy you bring to my life. At last, thank you to all my colleagues and friends at the College of Pharmacy. I made great friendships during my journey as a graduate student that I hope to maintain throughout my life. 5 DEDICATION To my father, Roberto Lizarraga, Who inspired me to pursuit a career in science Thank you for all your dedication and guidance 6 TABLE OF CONTENTS LIST OF FIGURES.......................................................................................................................................8 LIST OF ABBREVIATIONS...........................................................................................................................9 ABSTRACT .............................................................................................................................................. 12 CHAPTER 1: INTRODUCTION .................................................................................................................. 14 1.1 MDMA: THE PROTOTYPE CLUB DRUG......................................................................................................14 1.1.1 History ...........................................................................................................................................14 1.1.2 Epidemiology.................................................................................................................................15 1.1.3 Chemical Structure, Route of Administration and Dosage ............................................................16 1.2 PHARMACOKINETICS OF MDMA..............................................................................................................19 1.2.1 MDMA Metabolism and Potential Bioactivation ..........................................................................20 1.3 PHARMACOLOGY OF MDMA ...................................................................................................................27 1.3.1 Mechanism of Action.....................................................................................................................27 1.3.1 Acute Effects and Toxicity..............................................................................................................32 1.4 MECHANISMS OF ACUTE MDMA TOXICITY, AN EMPHASIS ON HYPERTHERMIA AND THE 5-HT BEHAVIORAL SYNDROME.........................................................................................................................33 1.4.1 Hyperthermia ................................................................................................................................33 1.4.2 The 5-HT behavioral syndrome......................................................................................................42 1.5 MECHANISMS OF LONG-TERM MDMA NEUROTOXICITY.........................................................................45 1.5.1 General Comments on Neurotoxicity ............................................................................................45 1.5.2 MDMA Neurotoxicity in Experimental Animals.............................................................................47 1.5.3 Evidence of Serotonergic Neurotoxicity in Ecstasy Users ..............................................................51 1.5.4 Molecular Mechanisms of MDMA-Mediated Neurotoxicity .........................................................52 1.5.4.1 Oxidative Stress................................................................................................................................. 52 1.5.4.2 DA Contributions............................................................................................................................... 59 1.5.4.3 The Role of Quinones in MDMA Neurotoxicity ................................................................................. 60 1.5.4.4 The Involvement of Serotonin Transporters ..................................................................................... 66 1.5.4.5 Contributions of Vesicular Transport to MDMA Neurotoxicity ......................................................... 69 1.6 DISSERTATION AIMS ................................................................................................................................71 CHAPTER 2: MATERIALS AND METHODS ................................................................................................75 2.1 MATERIALS ..............................................................................................................................................75 2.1.1 Chemicals and Reagents................................................................................................................75 2.1.2 Animals and Dose Regimen...........................................................................................................76 2.1.2.1 SERT Deficiency in Rats...................................................................................................................... 76 2.1.2.2 Pharmacological Inhibition of VMAT2 in Rats ................................................................................... 76 2.2 METHODS ................................................................................................................................................77 2.2.1 Confirmation of VMAT2 Inhibition by Ro4-1284 ...........................................................................77
Load more

Recommended publications
  • Journal of Biological Rhythms Official Publication of the Society for Research on Biological Rhythms
    Journal of Biological Rhythms Official Publication of the Society for Research on Biological Rhythms Volume 16, Issue 6 December 2001 EDITORIAL Pebbles of Truth 515 Martin Zatz FEATURE Review Clockless Yeast and the Gears of the Clock: How Do They Mesh? 516 Ruben Baler ARTICLES Resetting of the Circadian Clock by Phytochromes 523 and Cryptochromes in Arabidopsis Marcelo J. Yanovsky, M. Agustina Mazzella, Garry C. Whitelam, and Jorge J. Casal Distinct Pharmacological Mechanisms Leading to c-fos 531 Gene Expression in the Fetal Suprachiasmatic Nucleus Lauren P. Shearman and David R. Weaver Daily Novel Wheel Running Reorganizes and 541 Splits Hamster Circadian Activity Rhythms Michael R. Gorman and Theresa M. Lee Temporal Reorganization of the Suprachiasmatic Nuclei 552 in Hamsters with Split Circadian Rhythms Michael R. Gorman, Steven M. Yellon, and Theresa M. Lee Light-Induced Resetting of the Circadian Pacemaker: 564 Quantitative Analysis of Transient versus Steady-State Phase Shifts Kazuto Watanabe, Tom Deboer, and Johanna H. Meijer Temperature Cycles Induce a Bimodal Activity Pattern in Ruin Lizards: 574 Masking or Clock-Controlled Event? A Seasonal Problem Augusto Foà and Cristiano Bertolucci LETTER Persistence of Masking Responses to Light in Mice Lacking Rods and Cones 585 N. Mrosovsky, Robert J. Lucas, and Russell G. Foster MEETING Eighth Meeting of the Society for Research on Biological Rythms 588 Index 589 Journal of Biological Rhythms Official Publication of the Society for Research on Biological Rhythms EDITOR-IN-CHIEF Martin Zatz FEATURES EDITORS ASSOCIATE EDITORS Larry Morin Michael Hastings SUNY, Stony Brook University of Cambridge Anna Wirz-Justice Ken-Ichi Honma University of Basel Hokkaido Univ School Medicine Michael Young Rockefeller University EDITORIAL BOARD Josephine Arendt Terry Page University of Surrey Vanderbilt University Charles A.
    [Show full text]
  • A Review of Effective ADHD Treatment Devin Hilla Grand Valley State University, [email protected]
    Grand Valley State University ScholarWorks@GVSU Honors Projects Undergraduate Research and Creative Practice 12-2015 Changing Behavior, Brain Differences, or Both? A Review of Effective ADHD Treatment Devin Hilla Grand Valley State University, [email protected] Follow this and additional works at: http://scholarworks.gvsu.edu/honorsprojects Part of the Medicine and Health Sciences Commons Recommended Citation Hilla, Devin, "Changing Behavior, Brain Differences, or Both? A Review of Effective ADHD Treatment" (2015). Honors Projects. 570. http://scholarworks.gvsu.edu/honorsprojects/570 This Open Access is brought to you for free and open access by the Undergraduate Research and Creative Practice at ScholarWorks@GVSU. It has been accepted for inclusion in Honors Projects by an authorized administrator of ScholarWorks@GVSU. For more information, please contact [email protected]. Running Head: EFFECTIVE ADHD TREATMENT 1 Changing Behavior, Brain Differences, or Both? A Review of Effective ADHD Treatment Devin Hilla Grand Valley State University Honors Senior Thesis EFFECTIVE ADHD TREATMENT 2 Abstract Much debate exists over the proper course of treatment for individuals with attention- deficit/hyperactivity disorder (ADHD). Stimulant medications, such as methylphenidate (e.g., Ritalin) and amphetamine (e.g., Adderall), have been shown to be effective in managing ADHD symptoms. More recently, non-stimulant medications, such as atomoxetine (e.g., Strattera), clonidine (e.g., Kapvay), and guanfacine (e.g., Intuniv), have provided a pharmacological alternative with potentially lesser side effects than stimulants. Behavioral therapies, like behavioral parent training, behavioral classroom management, and behavioral peer interventions, have shown long-term benefits for children with ADHD; however, the success of the short-term management of ADHD symptoms is not as substantial when compared with stimulant medications.
    [Show full text]
  • Gabab Regulation of Methamphetamine-Induced Associative Learning
    Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 2010 Gabab Regulation of Methamphetamine-Induced Associative Learning Robin Michelle Voigt Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Pharmacology Commons Recommended Citation Voigt, Robin Michelle, "Gabab Regulation of Methamphetamine-Induced Associative Learning" (2010). Dissertations. 38. https://ecommons.luc.edu/luc_diss/38 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 2010 Robin Michelle Voigt LOYOLA UNIVERSITY CHICAGO GABAB REGULATION OF METHAMPHETAMINE-INDUCED ASSOCIATIVE LEARNING A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL IN CANDIDACY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY PROGRAM IN MOLECULAR PHARMACOLOGY & THERAPEUTICS BY ROBIN MICHELLE VOIGT CHICAGO, IL DECEMBER 2010 Copyright by Robin Michelle Voigt, 2010 All rights reserved ACKNOWLEDGEMENTS Without the support of so many generous and wonderful individuals I would not have been able to be where I am today. First, I would like to thank my Mother for her belief that I could accomplish anything that I set my mind to. I would also like to thank my dissertation advisor, Dr. Celeste Napier, for encouraging and challenging me to be better than I thought possible. I extend gratitude to my committee members, Drs. Julie Kauer, Adriano Marchese, Micky Marinelli, and Karie Scrogin for their guidance and insightful input.
    [Show full text]
  • Current Research on Methamphetamine-Induced Neurotoxicity: Animal Models of Monoamine Disruption
    J Pharmacol Sci 92, 178 – 195 (2003) Journal of Pharmacological Sciences ©2003 The Japanese Pharmacological Society Critical Review Current Research on Methamphetamine-Induced Neurotoxicity: Animal Models of Monoamine Disruption Taizo Kita1,2, George C. Wagner3, and Toshikatsu Nakashima1,* 1Department of Pharmacology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 2Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawacho, Minamiku, Fukuoka 815-8511, Japan 3Department of Psychology, Rutgers, The State University, New Brunswick, NJ 08903, USA Received March 6, 2003 Abstract. Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH- induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypo- thesis is based on the observation of free radical formation and oxidative stress produced by auto- oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH- induced neurotoxicity has also been established including evidence of protection of bcl-2, expres- sion of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3.
    [Show full text]
  • Effects of Ayahuasca on Psychometric Measures of Anxiety, Panic-Like and Hopelessness in Santo Daime Members R.G
    Journal of Ethnopharmacology 112 (2007) 507–513 Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members R.G. Santos a,∗, J. Landeira-Fernandez b, R.J. Strassman c, V. Motta a, A.P.M. Cruz a a Departamento de Processos Psicol´ogicos B´asicos, Instituto de Psicologia, Universidade de Bras´ılia, Asa Norte, Bras´ılia-DF 70910-900, Brazil b Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA c Departamento de Psicologia, Pontif´ıcia Universidade Cat´olica do Rio de Janeiro, PUC-RJ, Brazil Received 21 December 2006; received in revised form 16 April 2007; accepted 18 April 2007 Available online 25 April 2007 Abstract The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1 h after the ingestion of the brew, in a double-blind, placebo-controlled procedure.
    [Show full text]
  • The Dopamine D2, but Not D3 Or D4, Receptor Subtype Is Essential for the Disruption of Prepulse Inhibition Produced by Amphetamine in Mice
    The Journal of Neuroscience, June 1, 1999, 19(11):4627–4633 The Dopamine D2, but not D3 or D4, Receptor Subtype is Essential for the Disruption of Prepulse Inhibition Produced by Amphetamine in Mice Rebecca J. Ralph,1 Geoffrey B. Varty,2 Michele A. Kelly,3 Yan-Min Wang,5 Marc G. Caron,5 Marcelo Rubinstein,6 David K. Grandy,4 Malcolm J. Low,3 and Mark A. Geyer1,2 Departments of 1Neuroscience and 2Psychiatry, University of California at San Diego, La Jolla, California 92093-0804, 3Vollum Institute and 4Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201, 5Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham North Carolina 27710, and 6Instituto de Investigaciones en Ingenieria´ Gene´ tica y Biologı´a Molecular, Consejo Nacional de Investigiones Cientı´ficas y Te´ cnicas y Departamento de Biologı´a, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina Brain dopamine (DA) systems are involved in the modulation of observed at baseline. AMPH significantly disrupted PPI in the the sensorimotor gating phenomenon known as prepulse inhi- D2 (1/1) mice but had no effect in the D2 (2/2) mice. After bition (PPI). The class of D2-like receptors, including the D2, AMPH treatment, both DA D3 and D4 receptor (1/1) and (2/2) D3, and D4 receptor subtypes, have all been implicated in the mice had significant disruptions in PPI. These findings indicate control of PPI via studies of DA agonists and antagonists in that the AMPH-induced disruption of PPI is mediated via the rats.
    [Show full text]
  • Rescue of Dopamine Transporter Function in Hypoinsulinemic Rats by a D2 Receptor–ERK-Dependent Mechanism
    The Journal of Neuroscience, February 22, 2012 • 32(8):2637–2647 • 2637 Cellular/Molecular Rescue of Dopamine Transporter Function in Hypoinsulinemic Rats by a D2 Receptor–ERK-Dependent Mechanism W. Anthony Owens,1* Jason M. Williams,3,6,7* Christine Saunders,4,6 Malcolm J. Avison,4,5,7# Aurelio Galli,3,6# and Lynette C. Daws1,2# Departments of 1Physiology and 2Pharmacology, The University of Texas Health Science Center, San Antonio, Texas 78229, and Departments of 3Molecular Physiology and Biophysics, 4Pharmacology, and 5Radiology and Radiological Sciences, 6Center for Molecular Neuroscience, and 7Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, Tennessee 37232 The dopamine (DA) transporter (DAT) is a major target for abused drugs and a key regulator of extracellular DA. A rapidly growing literature implicates insulin as an important regulator of DAT function. We showed previously that amphetamine (AMPH)-evoked DA release is markedly impaired in rats depleted of insulin with the diabetogenic agent streptozotocin (STZ). Similarly, functional magnetic resonance imaging experiments revealed that the blood oxygenation level-dependent signal following acute AMPH administration in STZ-treated rats is reduced. Here, we report that these deficits are restored by repeated, systemic administration of AMPH (1.78 mg/kg, every other day for 8 d). AMPH stimulates DA D2 receptors indirectly by increasing extracellular DA. Supporting a role for D2 receptors in mediating this “rescue,” the effect was completely blocked by pre-treatment of STZ-treated rats with the D2 receptor antagonist raclopride before systemic AMPH. D2 receptors regulate DAT cell surface expression through ERK1/2 signaling. In ex vivo striatal preparations, repeated AMPH injections increased immunoreactivity of phosphorylated ERK1/2 (p-ERK1/2) in STZ-treated but not control rats.
    [Show full text]
  • A Study in D1 and D2 Receptor Knock-Out Mice
    The Journal of Neuroscience, November 1, 2002, 22(21):9604–9611 Differential Effects of Direct and Indirect Dopamine Agonists on Prepulse Inhibition: A Study in D1 and D2 Receptor Knock-Out Mice Rebecca J. Ralph-Williams,1 Virginia Lehmann-Masten,2 Veronica Otero-Corchon,3 Malcolm J. Low,3,4 and Mark A. Geyer2 1Alcohol and Drug Abuse Research Center, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478, 2Department of Psychiatry, University of California, San Diego, La Jolla, California 92093-0804, 3Vollum Institute and 4Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97201 Stimulation of the dopamine (DA) system disrupts prepulse indirect agonist in mice. As reported previously, amphetamine inhibition (PPI) of the acoustic startle response. On the basis of (10 mg/kg) failed to disrupt PPI in D2R knock-out mice, sup- rat studies, it appeared that DA D2 receptors (D2Rs) rather than porting a unique role of the D2R in the modulation of PPI. D1 receptors (D1Rs) regulate PPI, albeit possibly in synergism Dizocilpine (0.3 mg/kg) induced similar PPI deficits in D1R and with D1Rs. To characterize the DA receptor modulation of PPI in D2R mutant mice, confirming that the influences of the NMDA another species, we tested DA D1R and D2R mutant mice with receptor on PPI are independent of D1Rs and D2Rs in rodents. direct and indirect DA agonists and with the glutamate receptor Thus, both D1Rs and D2Rs modulate aspects of PPI in mice in antagonist, dizocilpine (MK-801). Neither the mixed D1/D2 ag- a manner that differs from dopaminergic modulation in rats.
    [Show full text]
  • SCH23390 Reduces Methamphetamine Self-Administration and Prevents Methamphetamine-Induced Striatal LTD
    International Journal of Molecular Sciences Article SCH23390 Reduces Methamphetamine Self-Administration and Prevents Methamphetamine-Induced Striatal LTD Yosef Avchalumov 1, Wulfran Trenet 1, Juan Piña-Crespo 2 and Chitra Mandyam 1,3,* 1 VA San Diego Healthcare System, San Diego, CA 92161, USA; [email protected] (Y.A.); [email protected] (W.T.) 2 Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA; [email protected] 3 Department of Anesthesiology, University of California San Diego, San Diego, CA 92161, USA * Correspondence: [email protected] Received: 31 July 2020; Accepted: 2 September 2020; Published: 5 September 2020 Abstract: Extended-access methamphetamine self-administration results in unregulated intake of the drug; however, the role of dorsal striatal dopamine D1-like receptors (D1Rs) in the reinforcing properties of methamphetamine under extended-access conditions is unclear. Acute (ex vivo) and chronic (in vivo) methamphetamine exposure induces neuroplastic changes in the dorsal striatum, a critical region implicated in instrumental learning. For example, methamphetamine exposure alters high-frequency stimulation (HFS)-induced long-term depression in the dorsal striatum; however, the effect of methamphetamine on HFS-induced long-term potentiation (LTP) in the dorsal striatum is unknown. In the current study, dorsal striatal infusion of SCH23390, a D1R antagonist, prior to extended-access methamphetamine self-administration reduced methamphetamine addiction-like behavior. Reduced
    [Show full text]
  • Minireview the Pharmacological Case for Cannabigerol
    1521-0103/376/2/204–212$35.00 https://doi.org/10.1124/jpet.120.000340 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 376:204–212, February 2021 Copyright ª 2021 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. Minireview The Pharmacological Case for Cannabigerol Rahul Nachnani, Wesley M. Raup-Konsavage, and Kent E. Vrana Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania Received September 15, 2020; accepted November 4, 2020 ABSTRACT Downloaded from Medical cannabis and individual cannabinoids, such as D9- antibacterial activity. There is growing interest in the commercial tetrahydrocannabinol (D9-THC) and cannabidiol (CBD), are re- use of this unregulated phytocannabinoid. This review focuses ceiving growing attention in both the media and the scientific on the unique pharmacology of CBG, our current knowledge literature. The Cannabis plant, however, produces over 100 of its possible therapeutic utility, and its potential toxicolog- different cannabinoids, and cannabigerol (CBG) serves as the ical hazards. precursor molecule for the most abundant phytocannabinoids. jpet.aspetjournals.org CBG exhibits affinity and activity characteristics between SIGNIFICANCE STATEMENT D9-THC and CBD at the cannabinoid receptors but appears Cannabigerol is currently being marketed as a dietary supple- to be unique in its interactions with a-2 adrenoceptors and ment and, as with cannabidiol (CBD) before, many claims are 5-hydroxytryptamine (5-HT1A). Studies indicate that CBG may being made about its benefits. Unlike CBD, however, little have therapeutic potential in treating neurologic disorders research has been performed on this unregulated molecule, (e.g., Huntington disease, Parkinson disease, and multiple and much of what is known warrants further investigation to sclerosis) and inflammatory bowel disease, as well as having identify potential areas of therapeutic uses and hazards.
    [Show full text]
  • Mechanisms of Cocaine Abuse and Toxicity
    Mechanisms of Cocaine Abuse and Toxicity U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse, and Mental Health Administration I Mechanisms of Cocaine Abuse and Toxicity Editors: Doris Clouet, Ph.D. Khursheed Asghar, Ph.D. Roger Brown, Ph.D. Division of Preclinical Research National Institute on Drug Abuse NIDA Research Monograph 88 1988 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 NIDA Research Monographs are prepared by the research divisions of the National Institute on Drug Abuse and published by its Office of Science. The primary objective of the series is to provide critical reviews of research problem areas and techniques, the content of state-of-the-art conferences, and integrative research reviews. Its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community. Editorial Advisors MARTIN W. ADLER, Ph.D. MARY L. JACOBSON Temple University School of Medicine National Federation of Parents for Philadelphia,Pennsylvania Drug-Free Youth Omaha, Nebraska SYDNEY ARCHER, Ph.D. Rensselaer Polytechnic lnstitute Troy, New York REESE T. JONES, M.D. Langley Porter Neuropsychiatric lnstitute RICHARD E. BELLEVILLE, Ph.D. San Francisco, California NB Associates, Health Sciences RockviIle, Maryland DENISE KANDEL, Ph.D. KARST J. BESTEMAN College of Physicians and Surgeons of Alcohol and Drug Problems Association Columbia University of North America New York, New York Washington, D.C. GILBERT J.
    [Show full text]
  • Adrenergic Agonists
    ADRENERGIC AGONISTS • Course: Integrated Therapeutics 1 • Lecturer: Dr. E. Konorev • Date: September 16, 2010 • Materials on: Exam #2 • Required reading: Katzung, Chapter 9 1 ADRENERGIC NEUROTRANSMISSION Pre-Synaptic Neuron Synapse Post-Synaptic Neuron Tyrosine Reuptake Tyrosine Hydroxylase NE -receptors NE -receptors MAO 2-autoreceptors NE = norepinephrine 2 REGULATION OF ADRENERGIC TRANSMISSION BY PRESYNAPTIC RECEPTORS • Autoreceptors (2) • Heteroreceptors 3 CATECHOLAMINES AS ADRENERGIC NEUROTRANSMITTERS Sympathetic Neurotransmitters 4 TYPES OF ADRENERGIC RECEPTORS • -AR defined by the following potency norepinephrine > epinephrine >> isoproterenol – Subtypes of were originally identified by selective antagonists • 1 blocked by prazosin • 2 blocked by yohimbine – Further subtypes are now known – Selective 1 and 2 agonists are now known Dr. Raymond Ahlquist (1914-1989), suggested that CA act via two principal types of AR, and (1948) 5 TYPES OF ADRENERGIC RECEPTORS • -AR defined by the following potency isoproterenol >> epinephrine > norepinephrine – 1 and 2 subtypes of determined by affinity • 1 affinity – epinephrine = norepinephrine • 2 affinity – epinephrine >> norepinephrine – 3-AR subtype has now been described • Dopamine (D) receptors – Distinct from and receptors – Important in brain, splanchnic and renal vasculature 6 TYPES OF ADRENERGIC RECEPTORS Gene on Receptor Agonist Antagonist Effects Chromosome 1 type Phenylephrine Prazosin ↑ IP3, DAG common to all 1A C5 1B C8 1D C20 2 type Clonidine Yohimbine cAMP common to all
    [Show full text]