DOCSLIB.ORG

Valeriana Officinalis and Melissa Officinalis Extracts Normalize Brain Levels of GABA and Glutamate Altered by Chronic Stress

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Valeriana Officinalis and Melissa Officinalis Extracts Normalize Brain Levels of GABA and Glutamate Altered by Chronic Stress ISSN: 2572-4053 Scaglione and Zangara. J Sleep Disord Manag 2017, 3:016 DOI: 10.23937/2572-4053.1510016 Volume 3 | Issue 1 Journal of Open Access Sleep Disorders and Management RESEARCH ARTICLE Valeriana Officinalis and Melissa Officinalis Extracts Normalize Brain Levels of GABA and Glutamate Altered by Chronic Stress Francesco Scaglione1* and Andrea Zangara2,3 1Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy 2Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Australia 3Natural Power Meds Consulting, Barcelona, Spain *Corresponding author: Prof. Francesco Scaglione, MD, PhD, Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, 20129-Milan, Italy, Tel: ++39-0250317073, Fax: ++39-0250317050, E-mail: [email protected] Abstract Keywords Despite being traditionally used herbals to treat mild anxiety Valeriana officinalis, Melissa officinalis, GABA, Glutamate, and sleep disorders, Valeriana officinalis and Melissa officina- Sleep lis mechanism of action is not fully understood. While the pat- tern of mood modulation of both herbals suggests the involve- ment of the Gamma-Aminobutyric Acid (GABA) ergic system, Introduction other changes in the neurotransmitters pathways can provide Sleep loss and sleep disorders are among the most an explanation for the clinical effects. The aim of this study was to examine the combined mechanism of action of the two ex- common health problems. Surveys report that approx- tracts in order to explain the anxiolytic and calming effects that imately 30% to 40% of adults have problems initiat- may facilitate sleep induction and improve sleep quality in pa- ing or maintaining sleep [1-3]. About 10% to 15% of tients with mild to moderate sleep disturbances. These effects adults report severe problems, and this statistic rises have been previously reported in the literature for a botanical product combining 120 mg Valeriana officinalis and 80 mg of up to 25% in the elderly [2]. Insomnia is found in up Melissa officinalis standardized extracts (Songha® Night). To to 69% of patients attending primary care clinics and assess mechanism of action we employed the Unpredictable more common with chronic medical conditions [3,4]. Chronic Mild Stress (UCMS) animal model, as it has strong Chronic sleep loss has serious consequences for health, predictive validity. Brain GABA and glutamate levels were performance, and safety [5]. Anxiety and stress disor- sampled using a microdialysis technique and measured by HPLC. Additional in vitro experiments investigated the effects ders represent a range of conditions that include gen- of the extracts on Group II Metabotropic Glutamate Receptors eralized anxiety, panic attacks, post-traumatic stress (mGlu2) binding and GABA Transaminase (GABA-T) activity. disorder, obsessive-compulsive syndrome, and social Results indicate that the two extracts together exert a func- phobias. All of them lead to sleep disturbances and tional synergism leading to normalization of brain levels of GABA and glutamate altered by stress. In vitro experiments interfere with cognitive functions [6]. Unfortunately, reveal that the combination of both extracts could inhibit GA- there is only limited evidence to support the efficacy BA-T activity more effectively than the single extracts, and that of many of the commonly used remedies for insomnia, Valeriana officinalis binds mGlu2 receptors. Altogether these including antihistamines, chloral hydrate, barbiturates, results demonstrate a synergistic effect of Valeriana officinalis tryptophan, and melatonin [7]. Although benzodiaze- and Melissa officinalis standardized extracts on counteracting the alterations in neurotransmitter levels caused by chronic pines are known to be effective for insomnia, their clin- stress and support the tranquilizing and sleep inducing activity ical benefit is negligible and similar to that found with of Songha® Night observed in clinical trials. exercise therapy alone [8]. Moreover, benzodiazepine receptor agonists chronic treatment is limited by con- Citation: Scaglione F, Zangara A (2017) Valeriana Officinalis and Melissa Officinalis Extracts Normalize Brain Levels of GABA and Glutamate Altered by Chronic Stress. J Sleep Disord Manag 3:016. doi.org/10.23937/2572- 4053.1510016 Received: May 05, 2017: Accepted: September 16, 2017: Published: September 18, 2017 Copyright: © 2017 Scaglione F, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Scaglione and Zangara. J Sleep Disord Manag 2017, 3:016 • Page 1 of 7 • DOI: 10.23937/2572-4053.1510016 ISSN: 2572-4053 cerns regarding long-term efficacy and the potential for Nervous System (CNS). For this reason, we measured abuse, dependence, and adverse side effects, including the levels of glutamate and GABA in the brain of rats an increased risk of motor vehicle accidents, falls, and exposed to chronic stress and treated with either VAL, fractures [7]. For these reasons, many people with sleep or MEL, or a combination of both extracts. We select- disorders resort to complementary medicines, including ed the Unpredictable Chronic Mild Stress (UCMS) ani- herbal extracts [9]. mal model, as most effects of UCMS can be reversed by antidepressant agents, illustrating a strong predictive Two herbal extracts, Valeriana officinalis (VAL) and validity [35]. Melissa officinalis (MEL) have been commonly used to treat mild anxiety and sleep disorders [10,11]. The Materials and Methods extract of the root of VAL, a flowering plant, has been widely used to treat sleep disorders in Europe for de- Animals cades [10] and is becoming increasingly popular in the Six to eight-week-old female Wistar rats were pur- United States as a self-prescribed treatment for insom- chased from Charles River (Calco, Italy). Animals were nia. In a national survey, approximately two million left to acclimate for 1 week before entering the study. adults reported using valerian in the past week [11]. Rats were then divided in five groups (ten animals per The perennial lemon-scented herb MEL (synonym group) and stressed using the UCMS technique. Institu- lemon balm) has been in use as a pan-cultural medicinal tional and national guide for the care and use of labora- treatment for more than two millennia. Its traditional tory animals was followed (Prot. N. 15-2013). indications have included general beneficial effects on Materials the brain as a treatment for memory disorders [12] and for “all complaints supposed to proceed from a disor- MEL and VAL standardized extracts were supplied by dered state of the nervous system” [13]. Contemporary Ginsana SA (Bioggio, Swizerland). The analytical mark- reports emphasize the sedative, spasmolytic, and anti- ers for VAL are valerenic acids, and the fixed ratio herbal bacterial effects of MEL, with indications encompassing drug:dry extract = 4.5:1; while the MEL analytical mark- nervous, gastrointestinal, and sleep disorders [14-16]. er is rosmarinic acid (> 1.8%) and the extract is stan- dardized on the fixed ratio herbal drug:dry extract = 5:1. The specific mechanisms of action responsible for the pharmacological effects of VAL and MEL have not Chemicals been fully elucidated, nevertheless, accumulating evi- L-[3,4-3H]-Glutamic acid (49.9 Ci/mmol) was obtained dence points towards both GABAergic and glutamater- from Perkin Elmer Life and Analytical Sciences, Inc. LC- gic actions of both extracts [10,17-24]. CG-I (2S,1S,2S)-2-(Carboxycyclopropyl)glycine and L-AP4 While GABA receptor binding activity is relatively (L-(+)-2-Amino-4-phosphonobutyric acid) were obtained well studied in anxiolytic botanicals, one of the other from Tocris Bioscience (Ellisville, MO). All other reagents mechanisms that induce GABA levels to increase in the were obtained from Sigma-Aldrich Co. brain and potentially cause anxiety reduction is the inhi- Stress procedures bition of the enzyme GABA-T [25-27]. The UCMS model involves the chronic sequential Anxiety-related cognitive and behavioral disorders of- application of a variety of extremely mild stressors in a ten result from low levels of the inhibitory neurotransmit- random order, so that they are unpredictable. The stress ter GABA [28] and an increased glutamate release [29]. regimen is applied for three weeks. Different stressors A precise combination of 120 mg VAL and 80 mg MEL are presented: standardized extracts (Songha® Night) has been shown • to improve sleep quality in patients with mild to mod- Short periods (3 h) of food and water deprivations erate sleep disturbances and to have anxiolytic effects, • Confinement in a small tube (1 h) with no decrease in vigilance or mental performance, • Paired housing (exposure of a rat to another stressed no additive effect with alcohol in the psychomotor func- rat in the same cage) (2 h) tioning, and rare or inconsistent hangover symptoms, [30,31], as opposed to benzodiazepines and other sed- • Reversal of the dark/light cycle ative compounds. The neurotransmitters GABA and • 45° tilt cage (1 h) glutamate are both involved in the pathophysiology of sleep and mood disorders; published data point to an • Forced swim (30 min) increase of glutamate release and a deficit of GABA [28, • Housing with damp sawdust 29,32-34]. • Access to an empty bottle (2 h). Hence, we tested the hypothesis
Load more

Recommended publications
  • ON ATTRACTION of SLIME MOULD PHYSARUM POLYCEPHALUM to PLANTS with SEDATIVE PROPERTIES 1. Introduction Physarum Polycephalum Belo
    ON ATTRACTION OF SLIME MOULD PHYSARUM POLYCEPHALUM TO PLANTS WITH SEDATIVE PROPERTIES ANDREW ADAMATZKY Abstract. A plasmodium of acellular slime mould Physarum polycephalum is a large single cell with many nuclei. Presented to a configuration of attracting and repelling stimuli a plasmodium optimizes its growth pattern and spans the attractants, while avoiding repellents, with efficient network of protoplasmic tubes. Such behaviour is interpreted as computation and the plasmodium as an amorphous growing biologi- cal computer. Till recently laboratory prototypes of slime mould computing devices (Physarum machines) employed rolled oats and oat powder to represent input data. We explore alternative sources of chemo-attractants, which do not require a sophis- ticated laboratory synthesis. We show that plasmodium of P. polycephalum prefers sedative herbal tablets and dried plants to oat flakes and honey. In laboratory experi- ments we develop a hierarchy of slime-moulds chemo-tactic preferences. We show that Valerian root (Valeriana officinalis) is strongest chemo-attractant of P. polycephalum outperforming not only most common plants with sedative activities but also some herbal tablets. Keywords: Physarum polycephalum, slime mould, valerian, passion flower, hops, ver- vain, gentian, wild lettuce, chemo-attraction 1. Introduction Physarum polycephalum belongs to the species of order Physarales, subclass Myxo- gastromycetidae, class Myxomycetes, division Myxostelida. It is commonly known as a true, acellular or multi-headed slime mould. Plasmodium is a `vegetative' phase, single cell with a myriad of diploid nuclei. The plasmodium looks like an amorphous yellowish mass with networks of protoplasmic tubes. The plasmodium behaves and moves as a giant amoeba. It feeds on bacteria, spores and other microbial creatures and micro- particles (Stephenson & Stempen, 2000).
    [Show full text]
  • Yerevan State Medical University After M. Heratsi
    YEREVAN STATE MEDICAL UNIVERSITY AFTER M. HERATSI DEPARTMENT OF PHARMACY Balasanyan M.G. Zhamharyan A.G. Afrikyan Sh. G. Khachaturyan M.S. Manjikyan A.P. MEDICINAL CHEMISTRY HANDOUT for the 3-rd-year pharmacy students (part 2) YEREVAN 2017 Analgesic Agents Agents that decrease pain are referred to as analgesics or as analgesics. Pain relieving agents are also called antinociceptives. An analgesic may be defined as a drug bringing about insensibility to pain without loss of consciousness. Pain has been classified into the following types: physiological, inflammatory, and neuropathic. Clearly, these all require different approaches to pain management. The three major classes of drugs used to manage pain are opioids, nonsteroidal anti-inflammatory agents, and non opioids with the central analgetic activity. Narcotic analgetics The prototype of opioids is Morphine. Morphine is obtained from opium, which is the partly dried latex from incised unripe capsules of Papaver somniferum. The opium contains a complex mixture of over 20 alkaloids. Two basic types of structures are recognized among the opium alkaloids, the phenanthrene (morphine) type and the benzylisoquinoline (papaverine) type (see structures), of which morphine, codeine, noscapine (narcotine), and papaverine are therapeutically the most important. The principle alkaloid in the mixture, and the one responsible for analgesic activity, is morphine. Morphine is an extremely complex molecule. In view of establish the structure a complicated molecule was to degrade the: compound into simpler molecules that were already known and could be identified. For example, the degradation of morphine with strong base produced methylamine, which established that there was an N-CH3 fragment in the molecule.
    [Show full text]
  • Vademecum Agrovet Market Animal Health
    Vademecum Agrovet Market Animal Health We are a Peruvian company focused on the development, production and commercialization of veterinary products, driving its technical and creative development to meet the needs of veterinarians and stock farmers with unique products of high quality. www.agrovetmarket.com Mission l Products of Unique Class Provide veterinary, nutritional and farmaceutical products of unique class; developed in a creative and innovative way, under high standards of quality that allow us to reach international markets and consolidate locally through the formal stablishment of strategical alliances. Antibiotics Line of large animals am Line of companion animals ac Line of poultry and swine av www.agrovetmarket.com Antibiotics ® Agrogenta 11 | Vetigen 11 Injectable Solution Broad-spectrum aminoglycoside Composition: Gentamicin (as sulphate) 110 mg, excipients q.s. ad 1 mL. Indications: Treatment and prevention of infections caused by microorganisms sensitive to gentamicin (of the urogenital, respiratory and gastrointestinal systems). Also useful in cases of mastitis, metritis, post-operatory and cutaneous infections, septicemias, among others.. Dosage and Administration: Cattle, horse, sheep, goat, swine, camelid: 1 mL/27.5 kg of b.w.; young animals, dogs and cats: 1 mL/14 kg; poultry: 0.1 mL/1.4 kg; every 24 hours for 3 to 5 consecutive days by subcutaneous or intramuscular route. Intrauterine or intra-mammary route: Cows: 2 mL diluted in 20 mL of physiological saline solution for 3 to 5 days. Mares: 20 mL diluted in 200 - 500 mL of physiological saline solution for 3 to 5 days (only intrauterine route). Commercial Presentation: Bottle x 100 mL and 250 mL.
    [Show full text]
  • Valerenic Acid Potentiates and Inhibits GABAA Receptors: Molecular Mechanism and Subunit Specificity
    ARTICLE IN PRESS + MODEL Neuropharmacology xx (2007) 1e10 www.elsevier.com/locate/neuropharm Valerenic acid potentiates and inhibits GABAA receptors: Molecular mechanism and subunit specificity S. Khom a, I. Baburin a, E. Timin a, A. Hohaus a, G. Trauner b, B. Kopp b, S. Hering a,* a Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria b Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria Received 8 December 2006; received in revised form 11 April 2007; accepted 30 April 2007 Abstract Valerian is a commonly used herbal medicinal product for the treatment of anxiety and insomnia. Here we report the stimulation of chloride currents through GABAA receptors (IGABA) by valerenic acid (VA), a constituent of Valerian. To analyse the molecular basis of VA action, we expressed GABAA receptors with 13 different subunit compositions in Xenopus oocytes and measured IGABA using the two-microelectrode voltage-clamp technique. We report a subtype-dependent stimulation of IGABA by VA. Only channels incorporating b2 or b3 subunits were stimulated by VA. Replacing b2/3 by b1 drastically reduced the sensitivity of the resulting GABAA channels. The stimulatory effect of VA on a1b2 receptors was substantially reduced by the point mutation b2N265S (known to inhibit loreclezole action). Mutating the corresponding residue of b1 (b1S290N) induced VA sensitivity in a1b1S290N comparable to a1b2 receptors. Modulation of IGABA was not significantly dependent on incorporation of a1, a2, a3 or a5 subunits. VA displayed a significantly lower efficiency on channels incorporating a4 subunits. IGABA modulation by VA was not g subunit dependent and not inhibited by flumazenil (1 mM).
    [Show full text]
  • Receives Fda Approval for the Treatment of Insomnia
    AMBIEN CR™ (ZOLPIDEM TARTRATE EXTENDED-RELEASE TABLETS) CIV RECEIVES FDA APPROVAL FOR THE TREATMENT OF INSOMNIA First and Only Extended-Release Prescription Sleep Medication Indicated for Sleep Induction and Maintenance Covers Broad Insomnia Population Paris, France, September 6, 2005 - Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that the U.S. Food and Drug Administration (FDA) has approved AMBIEN CR™ (zolpidem tartrate extended-release tablets) CIV, a new extended-release formulation of the number ® one prescription sleep aid, AMBIEN (zolpidem tartrate) CIV, for the treatment of insomnia. AMBIEN CR is non-narcotic and a non-benzodiazepine, formulated to offer a similar safety profile to AMBIEN with a new indication for sleep maintenance, in addition to sleep induction. AMBIEN CR is the first and only extended-release prescription sleep medication to help people with insomnia fall asleep fast and maintain sleep with no significant decrease in next day performance. AMBIEN CR, a bi-layered tablet, is delivered in two stages. The first layer dissolves quickly to induce sleep. The second layer is released more gradually into the body to help provide more continuous sleep. “Insomnia is a significant public health problem, affecting millions of Americans. Insomnia impacts daily activities and is associated with increased health care costs,” said James K. Walsh, PhD, Executive Director and Senior Scientist, Sleep Medicine and Research Center at St. Luke's Hospital in St. Louis, Missouri. “Helping patients stay asleep is recognized as being as important as helping them fall asleep,” said Walsh. “Ambien CR has shown evidence of promoting sleep onset and more continuous sleep".
    [Show full text]
  • Plant-Based Medicines for Anxiety Disorders, Part 2: a Review of Clinical Studies with Supporting Preclinical Evidence
    CNS Drugs 2013; 24 (5) Review Article Running Header: Plant-Based Anxiolytic Psychopharmacology Plant-Based Medicines for Anxiety Disorders, Part 2: A Review of Clinical Studies with Supporting Preclinical Evidence Jerome Sarris,1,2 Erica McIntyre3 and David A. Camfield2 1 Department of Psychiatry, Faculty of Medicine, University of Melbourne, Richmond, VIC, Australia 2 The Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, VIC, Australia 3 School of Psychology, Charles Sturt University, Wagga Wagga, NSW, Australia Correspondence: Jerome Sarris, Department of Psychiatry and The Melbourne Clinic, University of Melbourne, 2 Salisbury Street, Richmond, VIC 3121, Australia. Email: [email protected], Acknowledgements Dr Jerome Sarris is funded by an Australian National Health & Medical Research Council fellowship (NHMRC funding ID 628875), in a strategic partnership with The University of Melbourne, The Centre for Human Psychopharmacology at the Swinburne University of Technology. Jerome Sarris, Erica McIntyre and David A. Camfield have no conflicts of interest that are directly relevant to the content of this article. 1 Abstract Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. Thus, our aim was to provide a comprehensive narrative review of plant-based medicines that have clinical and/or preclinical evidence of anxiolytic activity. We present the article in two parts. In part one, we reviewed herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In this current article (part two), we review herbal medicines for which there have been both preclinical and clinical investigations for anxiolytic activity.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,101,662 B2 Tamarkin Et Al
    USOO91 01662B2 (12) United States Patent (10) Patent No.: US 9,101,662 B2 Tamarkin et al. (45) Date of Patent: *Aug. 11, 2015 (54) COMPOSITIONS WITH MODULATING A61K 47/32 (2013.01); A61 K9/0014 (2013.01); AGENTS A61 K9/0031 (2013.01); A61 K9/0034 (2013.01); A61 K9/0043 (2013.01); A61 K (71) Applicant: Foamix Pharmaceuticals Ltd., Rehovot 9/0046 (2013.01); A61 K9/0048 (2013.01); (IL) A61 K9/0056 (2013.01) (72) Inventors: Dov Tamarkin, Macabim (IL); Meir (58) Field of Classification Search Eini, Ness Ziona (IL); Doron Friedman, CPC ........................................................ A61 K9/12 Karmei Yosef (IL); Tal Berman, Rishon See application file for complete search history. le Ziyyon (IL); David Schuz, Gimzu (IL) (56) References Cited (73) Assignee: Foamix Pharmaceuticals Ltd., Rehovot U.S. PATENT DOCUMENTS (IL) 1,159,250 A 11/1915 Moulton (*) Notice: Subject to any disclaimer, the term of this 1,666,684 A 4, 1928 Carstens patent is extended or adjusted under 35 1924,972 A 8, 1933 Beckert 2,085,733. A T. 1937 Bird U.S.C. 154(b) by 0 days. 2,390,921 A 12, 1945 Clark This patent is Subject to a terminal dis 2,524,590 A 10, 1950 Boe claimer. 2,586.287 A 2/1952 Apperson 2,617,754 A 1 1/1952 Neely 2,767,712 A 10, 1956 Waterman (21) Appl. No.: 14/045,528 2.968,628 A 1/1961 Reed 3,004,894 A 10/1961 Johnson et al. (22) Filed: Oct. 3, 2013 3,062,715 A 11/1962 Reese et al.
    [Show full text]
  • Herbal Remedies and Their Possible Effect on the Gabaergic System and Sleep
    nutrients Review Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep Oliviero Bruni 1,* , Luigi Ferini-Strambi 2,3, Elena Giacomoni 4 and Paolo Pellegrino 4 1 Department of Developmental and Social Psychology, Sapienza University, 00185 Rome, Italy 2 Department of Neurology, Ospedale San Raffaele Turro, 20127 Milan, Italy; [email protected] 3 Sleep Disorders Center, Vita-Salute San Raffaele University, 20132 Milan, Italy 4 Department of Medical Affairs, Sanofi Consumer HealthCare, 20158 Milan, Italy; Elena.Giacomoni@sanofi.com (E.G.); Paolo.Pellegrino@sanofi.com (P.P.) * Correspondence: [email protected]; Tel.: +39-33-5607-8964; Fax: +39-06-3377-5941 Abstract: Sleep is an essential component of physical and emotional well-being, and lack, or dis- ruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control.
    [Show full text]
  • Prohibited Substances List
    Prohibited Substances List This is the Equine Prohibited Substances List that was voted in at the FEI General Assembly in November 2009 alongside the new Equine Anti-Doping and Controlled Medication Regulations(EADCMR). Neither the List nor the EADCM Regulations are in current usage. Both come into effect on 1 January 2010. The current list of FEI prohibited substances remains in effect until 31 December 2009 and can be found at Annex II Vet Regs (11th edition) Changes in this List : Shaded row means that either removed or allowed at certain limits only SUBSTANCE ACTIVITY Banned Substances 1 Acebutolol Beta blocker 2 Acefylline Bronchodilator 3 Acemetacin NSAID 4 Acenocoumarol Anticoagulant 5 Acetanilid Analgesic/anti-pyretic 6 Acetohexamide Pancreatic stimulant 7 Acetominophen (Paracetamol) Analgesic/anti-pyretic 8 Acetophenazine Antipsychotic 9 Acetylmorphine Narcotic 10 Adinazolam Anxiolytic 11 Adiphenine Anti-spasmodic 12 Adrafinil Stimulant 13 Adrenaline Stimulant 14 Adrenochrome Haemostatic 15 Alclofenac NSAID 16 Alcuronium Muscle relaxant 17 Aldosterone Hormone 18 Alfentanil Narcotic 19 Allopurinol Xanthine oxidase inhibitor (anti-hyperuricaemia) 20 Almotriptan 5 HT agonist (anti-migraine) 21 Alphadolone acetate Neurosteriod 22 Alphaprodine Opiod analgesic 23 Alpidem Anxiolytic 24 Alprazolam Anxiolytic 25 Alprenolol Beta blocker 26 Althesin IV anaesthetic 27 Althiazide Diuretic 28 Altrenogest (in males and gelidngs) Oestrus suppression 29 Alverine Antispasmodic 30 Amantadine Dopaminergic 31 Ambenonium Cholinesterase inhibition 32 Ambucetamide Antispasmodic 33 Amethocaine Local anaesthetic 34 Amfepramone Stimulant 35 Amfetaminil Stimulant 36 Amidephrine Vasoconstrictor 37 Amiloride Diuretic 1 Prohibited Substances List This is the Equine Prohibited Substances List that was voted in at the FEI General Assembly in November 2009 alongside the new Equine Anti-Doping and Controlled Medication Regulations(EADCMR).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,636.405 B2 Tamarkin Et Al
    USOO9636405B2 (12) United States Patent (10) Patent No.: US 9,636.405 B2 Tamarkin et al. (45) Date of Patent: May 2, 2017 (54) FOAMABLE VEHICLE AND (56) References Cited PHARMACEUTICAL COMPOSITIONS U.S. PATENT DOCUMENTS THEREOF M (71) Applicant: Foamix Pharmaceuticals Ltd., 1,159,250 A 1 1/1915 Moulton Rehovot (IL) 1,666,684 A 4, 1928 Carstens 1924,972 A 8, 1933 Beckert (72) Inventors: Dov Tamarkin, Maccabim (IL); Doron 2,085,733. A T. 1937 Bird Friedman, Karmei Yosef (IL); Meir 33 A 1683 Sk Eini, Ness Ziona (IL); Alex Besonov, 2,586.287- 4 A 2/1952 AppersonO Rehovot (IL) 2,617,754. A 1 1/1952 Neely 2,767,712 A 10, 1956 Waterman (73) Assignee: EMY PHARMACEUTICALs 2.968,628 A 1/1961 Reed ... Rehovot (IL) 3,004,894. A 10/1961 Johnson et al. (*) Notice: Subject to any disclaimer, the term of this 3,062,715. A 1 1/1962 Reese et al. tent is extended or adiusted under 35 3,067,784. A 12/1962 Gorman pa 3,092.255. A 6/1963 Hohman U.S.C. 154(b) by 37 days. 3,092,555 A 6/1963 Horn 3,141,821 A 7, 1964 Compeau (21) Appl. No.: 13/793,893 3,142,420 A 7/1964 Gawthrop (22) Filed: Mar. 11, 2013 3,144,386 A 8/1964 Brightenback O O 3,149,543 A 9/1964 Naab (65) Prior Publication Data 3,154,075 A 10, 1964 Weckesser US 2013/0189193 A1 Jul 25, 2013 3,178,352.
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • Zebrafish Behavioural Profiling Identifies GABA and Serotonin
    ARTICLE https://doi.org/10.1038/s41467-019-11936-w OPEN Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation Matthew N. McCarroll1,11, Leo Gendelev1,11, Reid Kinser1, Jack Taylor 1, Giancarlo Bruni 2,3, Douglas Myers-Turnbull 1, Cole Helsell1, Amanda Carbajal4, Capria Rinaldi1, Hye Jin Kang5, Jung Ho Gong6, Jason K. Sello6, Susumu Tomita7, Randall T. Peterson2,10, Michael J. Keiser 1,8 & David Kokel1,9 1234567890():,; Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity—a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish. 1 Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA. 2 Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
    [Show full text]