Ergot Alkaloids As Dopamine Agonists: Comparison in Two Rodent Models
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Evidence for the Involvement of Spinal Cord 1 Adrenoceptors in Nitrous
Anesthesiology 2002; 97:1458–65 © 2002 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Evidence for the Involvement of Spinal Cord ␣ 1 Adrenoceptors in Nitrous Oxide–induced Antinociceptive Effects in Fischer Rats Ryo Orii, M.D., D.M.Sc.,* Yoko Ohashi, M.D.,* Tianzhi Guo, M.D.,† Laura E. Nelson, B.A.,‡ Toshikazu Hashimoto, M.D.,* Mervyn Maze, M.B., Ch.B.,§ Masahiko Fujinaga, M.D.ʈ Background: In a previous study, the authors found that ni- opioid peptide release in the brain stem, leading to the trous oxide (N O) exposure induces c-Fos (an immunohisto- 2 activation of the descending noradrenergic inhibitory chemical marker of neuronal activation) in spinal cord ␥-ami- nobutyric acid–mediated (GABAergic) neurons in Fischer rats. neurons, which results in modulation of the pain–noci- 1 In this study, the authors sought evidence for the involvement ceptive processing in the spinal cord. Available evi- Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/97/6/1458/337059/0000542-200212000-00018.pdf by guest on 01 October 2021 ␣ of 1 adrenoceptors in the antinociceptive effect of N2O and in dence suggests that at the level of the spinal cord, there activation of GABAergic neurons in the spinal cord. appear to be at least two neuronal systems that are Methods: Adult male Fischer rats were injected intraperitone- involved (fig. 1). In one of the pathways, activation of ally with ␣ adrenoceptor antagonist, ␣ adrenoceptor antago- 1 2 ␣ nist, opioid receptor antagonist, or serotonin receptor antago- the 2 adrenoceptors produces either direct presynaptic nist and, 15 min later, were exposed to either air (control) or inhibition of neurotransmitter release from primary af- 75% N2O. -
Lysergic Acid on the Heart of Venus Mercenaria By
Brit. J. Pharmacol. (1962), 18, 440-450. ACTIONS OF DERIVATIVES OF -LYSERGIC ACID ON THE HEART OF VENUS MERCENARIA BY ANNE McCOY WRIGHT, MERILYN MOORHEAD AND J. H. WELSH From the Biological Laboratories, Harvard University, Cambridge, Massachusetts, U.S.A. (Received February 5, 1962) 5-Hydroxytryptamine and a number of (+ )-lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5-hydroxy- tryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethyl- amide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10"6 M lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one-half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5-hydroxytryptamine blocking action. This group consisted of 1-methyl-, I-acetyl-, and 2-bromo-lysergic acid diethylamide and 1-methyl- lysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10' M, and it blocked 5-hydroxytryptamine in a molar ratio of about one to one. During the early studies on the pharmacology of the heart of the mollusc, Venus mercenaria, certain of the ergot alkaloids were observed to have a remarkable excitatory action that was only very slowly reversed by washing (Welsh & Taub, 1948). -
The Serotonergic System in Migraine Andrea Rigamonti Domenico D’Amico Licia Grazzi Susanna Usai Gennaro Bussone
J Headache Pain (2001) 2:S43–S46 © Springer-Verlag 2001 MIGRAINE AND PATHOPHYSIOLOGY Massimo Leone The serotonergic system in migraine Andrea Rigamonti Domenico D’Amico Licia Grazzi Susanna Usai Gennaro Bussone Abstract Serotonin (5-HT) and induce migraine attacks. Moreover serotonin receptors play an impor- different pharmacological preventive tant role in migraine pathophysiolo- therapies (pizotifen, cyproheptadine gy. Changes in platelet 5-HT content and methysergide) are antagonist of are not casually related, but they the same receptor class. On the other may reflect similar changes at a neu- side the activation of 5-HT1B-1D ronal level. Seven different classes receptors (triptans and ergotamines) of serotoninergic receptors are induce a vasocostriction, a block of known, nevertheless only 5-HT2B-2C neurogenic inflammation and pain M. Leone • A. Rigamonti • D. D’Amico and 5HT1B-1D are related to migraine transmission. L. Grazzi • S. Usai • G. Bussone (౧) syndrome. Pharmacological evi- C. Besta National Neurological Institute, Via Celoria 11, I-20133 Milan, Italy dences suggest that migraine is due Key words Serotonin • Migraine • e-mail: [email protected] to an hypersensitivity of 5-HT2B-2C Triptans • m-Chlorophenylpiperazine • Tel.: +39-02-2394264 receptors. m-Chlorophenylpiperazine Pathogenesis Fax: +39-02-70638067 (mCPP), a 5-HT2B-2C agonist, may The 5-HT receptor family is distinguished from all other 5- Introduction 1 HT receptors by the absence of introns in the genes; in addi- tion all are inhibitors of adenylate cyclase [1]. Serotonin (5-HT) and serotonin receptors play an important The 5-HT1A receptor has a high selective affinity for 8- role in migraine pathophysiology. -
Pharmacognosy
Pharmacognosy Third stage Dr. Enass Najem 2nd semester Lec:8 ERGOT, ERGOT ALKALOIDS, AND LSD When the parasitic fungus Claviceps purpurea lives on rye and other cereal crops, a poisonous alkaloid and called ergot is produced. Ergot was the subject of great fear previously, because people who ate rye products infected with this, fungus experienced a strange and debilitating, and frequently lethal, disease. Ergot contains alkaloids that contract the blood vessels of arms and legs, preventing circulation of the blood, and gangrene results. Thus, people suffering from ergot poisoning lost their hands and legs without bleeding (ergotism), after they became darkened. Although it was well known that ergot was very dangerous, midwives in Europe were also using it for promotion of the contraction of the womb post-parturition. Subsequently, studies of the active principle(s) of ergot responsible for the contractions were initiated. The first alkaloid isolated in crystalline form was ergotinine , but it did not possess the uterocontracting activity. Ergotoxine was the first biologically active alkaloid isolated, and was shown to be a mixture of ergocristine, ergocornine, and related alkaloids. Ergotamine was isolated later in a pure form. The common skeleton of these ergot alkaloids is known as lysergic acid, and ergotamine comprises a structure based on lysergic acid coupled with a peptide moiety. The universal skeleton of the ergot alkaloids is known as the ergoline nucleus. It was shown by using cultivated Claviceps that the ergoline skeleton was derived biosynthetically from tryptophan and a C5 unit of mevalonic acid origin. 1 Pharmacognosy Simple lysergic acid amides, such as ergine and lysergic acid hydroxyethylamide, are obtained from the ergot that lives on wild grass. -
Selective Labeling of Serotonin Receptors Byd-[3H]Lysergic Acid
Proc. Nati. Acad. Sci. USA Vol. 75, No. 12, pp. 5783-5787, December 1978 Biochemistry Selective labeling of serotonin receptors by d-[3H]lysergic acid diethylamide in calf caudate (ergots/hallucinogens/tryptamines/norepinephrine/dopamine) PATRICIA M. WHITAKER AND PHILIP SEEMAN* Department of Pharmacology, University of Toronto, Toronto, Canada M5S 1A8 Communicated by Philip Siekevltz, August 18,1978 ABSTRACT Since it was known that d-lysergic acid di- The objective in this present study was to improve the se- ethylamide (LSD) affected catecholaminergic as well as sero- lectivity of [3H]LSD for serotonin receptors, concomitantly toninergic neurons, the objective in this study was to enhance using other drugs to block a-adrenergic and dopamine receptors the selectivity of [3HJISD binding to serotonin receptors in vitro by using crude homogenates of calf caudate. In the presence of (cf. refs. 36-38). We then compared the potencies of various a combination of 50 nM each of phentolamine (adde to pre- drugs on this selective [3H]LSD binding and compared these clude the binding of [3HJLSD to a-adrenoceptors), apmo ie, data to those for the high-affinity binding of [3H]serotonin and spiperone (added to preclude the binding of [3H[LSD to (39). dopamine receptors), it was found by Scatchard analysis that the total number of 3H sites went down to 300 fmol/mg, compared to 1100 fmol/mg in the absence of the catechol- METHODS amine-blocking drugs. The IC50 values (concentrations to inhibit Preparation of Membranes. Calf brains were obtained fresh binding by 50%) for various drugs were tested on the binding of [3HLSD in the presence of 50 nM each of apomorphine (A), from the Canada Packers Hunisett plant (Toronto). -
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol Drug Abuse and Mental Health Administration Pharmacology and Toxicology of Amphetamine and Related Designer Drugs Editors: Khursheed Asghar, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Errol De Souza, Ph.D. Addiction Research Center National Institute on Drug Abuse NIDA Research Monograph 94 1989 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 Pharmacology and Toxicology of Amphetamine and Related Designer Drugs ACKNOWLEDGMENT This monograph is based upon papers and discussion from a technical review on pharmacology and toxicology of amphetamine and related designer drugs that took place on August 2 through 4, 1988, in Bethesda, MD. The review meeting was sponsored by the Biomedical Branch, Division of Preclinical Research, and the Addiction Research Center, National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other matieral in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. -
Cabergoline Patient Handout
Cabergoline For the Patient: Cabergoline Other names: DOSTINEX® • Cabergoline (ca-BERG-go-leen) is used to treat cancers that cause the body to produce too much of a hormone called prolactin. Cabergoline helps decrease the size of the cancer and the production of prolactin. It is a tablet that you take by mouth. • Tell your doctor if you have ever had an unusual or allergic reaction to bromocriptine or other ergot derivatives, such as pergoline (PERMAX®) and methysergide (SANSERT®), before taking cabergoline. • Blood tests and blood pressure measurement may be taken while you are taking cabergoline. The dose of cabergoline may be changed based on the test results and/or other side effects. • It is important to take cabergoline exactly as directed by your doctor. Make sure you understand the directions. Take cabergoline with food. • If you miss a dose of cabergoline, take it as soon as you can if it is within 2 days of the missed dose. If it is over 2 days since your missed dose, skip the missed dose and go back to your usual dosing times. • Other drugs such as azithromycin (ZITHROMAX®), clarithromycin (BIAXIN®), erythromycin, domperidone, metoclopramide, and some drugs used to treat mental or mood problems may interact with cabergoline. Tell your doctor if you are taking these or any other drugs as you may need extra blood tests or your dose may need to be changed. Check with your doctor or pharmacist before you start or stop taking any other drugs. • The drinking of alcohol (in small amounts) does not appear to affect the safety or usefulness of cabergoline. -
Male Anorgasmia: from “No” to “Go!”
Male Anorgasmia: From “No” to “Go!” Alexander W. Pastuszak, MD, PhD Assistant Professor Center for Reproductive Medicine Division of Male Reproductive Medicine and Surgery Scott Department of Urology Baylor College of Medicine Disclosures • Endo – speaker, consultant, advisor • Boston Scientific / AMS – consultant • Woven Health – founder, CMO Objectives • Understand what delayed ejaculation (DE) and anorgasmia are • Review the anatomy and physiology relevant to these conditions • Review what is known about the causes of DE and anorgasmia • Discuss management of DE and anorgasmia Definitions Delayed Ejaculation (DE) / Anorgasmia • The persistent or recurrent delay, difficulty, or absence of orgasm after sufficient sexual stimulation that causes personal distress Intravaginal Ejaculatory Latency Time (IELT) • Normal (median) à 5.4 minutes (0.55-44.1 minutes) • DE à mean IELT + 2 SD = 25 minutes • Incidence à 2-11% • Depends in part on definition used J Sex Med. 2005; 2: 492. Int J Impot Res. 2012; 24: 131. Ejaculation • Separate event from erection! • Thus, can occur in the ABSENCE of erection! Periurethral muscle Sensory input - glans (S2-4) contraction Emission Vas deferens contraction Sympathetic input (T12-L1) SV, prostate contraction Bladder neck contraction Expulsion Bulbocavernosus / Somatic input (S1-3) spongiosus contraction Projectile ejaculation J Sex Med. 2011; 8 (Suppl 4): 310. Neurochemistry Sexual Response Areas of the Brain • Pons • Nucleus paragigantocellularis Neurochemicals • Norepinephrine, serotonin: • Inhibit libido, -
Hallucinogens: an Update
National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Hallucinogens: An Update 146 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Hallucinogens: An Update Editors: Geraline C. Lin, Ph.D. National Institute on Drug Abuse Richard A. Glennon, Ph.D. Virginia Commonwealth University NIDA Research Monograph 146 1994 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGEMENT This monograph is based on the papers from a technical review on “Hallucinogens: An Update” held on July 13-14, 1992. The review meeting was sponsored by the National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. -
Package Leaflet: Information for the Patient Dostinex® 0.5 Mg Tablets
Package leaflet: Information for the patient Dostinex® 0.5 mg Tablets cabergoline Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What Dostinex is and what it is used for 2. What you need to know before you take Dostinex 3. How to take Dostinex 4. Possible side effects 5 How to store Dostinex 6. Contents of the pack and other information 1. What Dostinex is and what it is used for - Dostinex contains the active ingredient cabergoline. This medicine belongs to a class of medicines called ‘dopamine agonists’. Dopamine is produced naturally in the body and helps to transmit messages to the brain. - Dostinex is used to stop breast milk production (lactation) soon after childbirth, stillbirth, abortion or miscarriage. It can also be used if you do not want to continue to breast-feed your baby once you have started. - Dostinex can also be used to treat other conditions caused by hormonal disturbance which can result in high levels of prolactin being produced. This includes lack of periods, infrequent and very light menstruation, periods in which ovulation does not occur and secretion of milk from your breast without breast-feeding. -
Early Piribedil Monotherapy of Parkinson's Disease
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Repositório Científico do Centro Hospitalar do Porto Movement Disorders Vol. 21, No. 12, 2006, pp. 2110–2115 © 2006 Movement Disorder Society Early Piribedil Monotherapy of Parkinson’s Disease: A Planned Seven-Month Report of the REGAIN Study Olivier Rascol, MD, PhD,1* Bruno Dubois, MD,2 Alexandre Castro Caldas, MD,3 Stephen Senn, MD,4 Susanna Del Signore, MD,5 and Andrew Lees, MD,6 on behalf of the Parkinson REGAIN Study Group 1INSERM U455, Clinical Investigation Center and Departments of Clinical Pharmacology and Neurosciences, Faculte´deMe´decine, Toulouse, France 2INSERM U610/Groupe Hospitalier Pitie´-Salpeˆtrie`re, Paris, France 3Instituto de Cie¨nsas da Sau`de, Lisbon, Portugal 4Department of Statistics, University of Glasgow, Glasgow, United Kingdom 5Institut de Recherches Internationales Servier, Courbevoie, France 6Royal Free and University College Medical School, University College London/Reta Lila, Weston Institute of Neurological Studies, London, United Kingdom Abstract: Piribedil is a D2 dopamine agonist, which has been significantly higher for piribedil (42%) than for placebo (14%) shown to improve symptoms of Parkinson’s disease (PD) when (OR ϭ 4.69; 95% CI ϭ 2.82–7.80; P Ͻ 0.001). Piribedil combined with L-dopa. The objective of this study was to significantly improved several UPDRS III subscores. UPDRS compare the efficacy of piribedil monotherapy to placebo in II improved on piribedil by Ϫ1.2 points, while it deteriorated patients with early PD over a 7-month period. Four hundred by 1.5 points on placebo (estimated effect ϭ 2.71; 95% CI ϭ and five early PD patients were randomized (double-blind) to 1.8–3.62; P Ͻ 0.0001). -
Effects of Drugs Acting on Cerebral 5-Hydroxytryptamine Mechanisms on Dopamine-Dependent Turning Behaviour in Mice
Br. J. Pharmac. (1976), 56, 77-85 EFFECTS OF DRUGS ACTING ON CEREBRAL 5-HYDROXYTRYPTAMINE MECHANISMS ON DOPAMINE-DEPENDENT TURNING BEHAVIOUR IN MICE J.A. MILSON Department of Pharmacology, University of Bristol Medical School, Bristol BS8 1TD C.J. PYCOCK Department of Neurology, Institute of Psychiatry, Denmark Hill, London SE5 8AF I The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2 Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3 Parachlorophenylalanine (3 x 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4 Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5 Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025- 0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6 The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5- hydroxytryptamine. 7 The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed. Introduction Recent behavioural studies have stressed an inter- terminals of the intact side and cause the animal to relation between 5-hydroxytryptamine'and the cate- circle towards the damaged'side.