DOCSLIB.ORG

By ZAHID HUSSAIN SIDDIK a Thesis Submitted for the Degree of Doctor

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
By ZAHID HUSSAIN SIDDIK a Thesis Submitted for the Degree of Doctor THE METABOLIC FATE OF LYSERGIC ACID DIETHYIAMIDE (LSi7) Iii LABORATORY AI,ItiALS by ZAHID HUSSAIN SIDDIK a thesis submitted for the degree of Doctor of Philosophy in the University of London September, 1975 Department of Biochemistry, St. Mary's Hospital Medical School, London, 42 ABSTRACT The metabolism of [i14lk C]-LSD has been studied in the Rhesus monkey, guinea pig and the rat. Marked species differences were observed in its excretion and metabolism. Rats excreted 71, of the dose (1 mg/kg intraperitoneally) in the faeces in 96 h, 16-, in the urine and 3.42, as 14CO2. Guinea pigs eliminated 40';‘, of the intraperitoneally administered 14C (1 mg/kg) in the faeces in 96 h, with 282, in the urine and as 14CO2. Monkeys receiving LSD (0.12 or 0.15 mg/kg) intra- muscularly, however, excreted 39-412c in the urine in 96 h and only 22-24;i, in the faeces. Biliary excretion of radioactivity (dose 1.33 mg/kg intravenously) in the rat was very rapid and 682i; appeared in 5 h whereas guinea pigs eliminated only 522L- (dose 0.5 mg/kg intravenously) in 6 h. Ring hydroxylation was extensive in the rat, glucuronides of 13- and 14- hydroxy-LSD being identified as the main excretory products. A third metabolite was identified as 2-oxo-LSD. 13-Hydroxy-LSD was a minor biliary metabolite as was lysergic acid monoethylamide (LAE) in the urine. Metabolites found in vivo were also present in the bile from isolated perfused livers in addition to some LSD. The perfusate and liver contained mostly LSD but also some glucuronides, 2-oxo-LSD, LAE, nor-LSD and probably "aromatised" 2-oxo-LSD. Ring hydroxylation and 2-oxidation, giving 14-hydroxy-LSD (as the glucuronide) and 2-oxo-LSD respectively, were major transformation products of LSD in the guinea pig. The glucuronide of 13-hydroxy-LSD, LAE and LSD were formed in small quantities. The monkey urine contained very little 13- and ik-hydroxy-LSD glucuronides. Some LAE, LSD and probably "aromatised" 2-oxo-LSD were also present. Of the fourteen compounds tested, seven, including LSD, altered the EEG pattern of the rabbit after intravenous administration. The stability of LSD and the fluorescence properties of LSD and a number of the metabolites have been investigated. 3 ;EEO;EMEt The work described in this thesis was carried out between October 1972 and June 1975 in the Department of Biochemistry, St. Mary's Hospital Medical School. I wish to thank Professor R.T. Williams, F.R.S., for the great interest he has shown throughout the course of this project. To Dr. L.G. Dring and Professor R.L. Smith, I am deeply grateful for their encouragement and helpful advice over the last three years. I will always appreciate the willingness of my fellow research workers, members of staff and the technical staff to assist practically whenever necessary and in providing helpful information. I will remember always Dr. R.B. Franklin for being a constant source of encouragement and practical advice during my first two years. I am indebted to Dr. R.D. Barnes, not only for carrying out the difficult task of synthesising the authentic compounds, but also for his many helpful discussions. I also wish to thank Dr. J.H.J. Durston for his supervision during the EEG study and for his analysis of the results. Miss Joan Caudrey and Miss Emilia Szigeti provided technical assistance during the BEG recordings and I am most grateful. My sincere thanks to Miss Rene Anderson for so capably typing this thesis. Finally, words can never adequately express my appreciation to members of my family for the understanding, patience and encouragement shown to me at all times. This work was carried out during the duration of a Research and Development Contract (NRC71/917) between the Medical Research Council and the Department of Biochemistry, St. Mary's Hospital Medical School, London, W2. 4 INDEX Abstract 2 Acknowledgements 3 Chapter One Introduction 5 Two Materials and Methods 67 Three Metabolism of [14C]-LSD in the Rat, Guinea Pig and Rhesus Monkey 101 Four The Fluorescence of LSD and its Derivatives and the Stability of LSD 175 Five The Effects of LSD and its Derivatives upon the Electroencephalogram (EEG) of Rabbits 204 Six Concluding Remarks and Scope for Future Metabolic Study of LSD 212 Appendix 216 References 225 5 CHAPTER ONE Introduction Contents page Introduction 6 Naturally Occurring Hallucinogens 6 History of Ergot and the Discovery of LSD-25 10 The Psychic Effects of LSD 12 Illicit Use of LSD 13 Therapeutic Use of LSD 17 Toxicological Studies of LSD 20 Behavioural Effects of LSD 24 Pharmacological Effects of LSD 26 The Mechanism of Action of LSD 28 Biochemical Effects of LSD 37 Structure-Activity Relationship 38 Chemical and Physical Aspects of LSD 41 General Aspects of the Metabolism of Foreign Compounds 43 Absorption, Binding and Distribution of LSD in the Body 46 Metabolism of LSD 51 In Vivo Studies 51 In Vitro Studies 54 Inhibitors of the Metabolism of LSD 57 The Metabolism of Compounds Structurally Related to LSD 57 Scope of the Present Study 66 Introduction (+)-Lysergic acid diethylamide (LSD, LSD-25, delysid, lysergide) is the most potent of a group of compounds which produce changes in thought, perception and mood and elicit visual and auditory hallucinations. These compounds were collectively named "phantastica" by Lewin in 1924. This designation never gained popularity especially among the English-speaking countries and so Hoffer and Osmond (1967) suggested the term "hallucinogens"; producers of hallucinations. True hallucinations, however, were rarely observed in the drug-induced states and this led to the designation "psychotomimetics", coined by Gerard in 1955. But the drugged state did not quite mimic the naturally occurring psychosis as suggested by the term psychotonimetic and it also became inappropriate. "Psychedelics", meaning mind-manifesting, was the term suggested by Osmond (1957) "because it is clear, euphonious and uncontaminated by other associations". "Psychotaraxics" (Caldwell, 1958), meaning mind-disturbers, "psychodysleptics" (Delay, 1959), "psycholytics", "mysticomimetics" (Valzelli, 1973), "psychotogens" and "illusinogen" (Cohen, 1970) are other designations that have been used. Of the above mentioned synonyms, psychotomimetic, psychedelic and hallucinogen are most often used in the scientific literature. kiaturally occurring Hallucinogens Most of the naturally occurring hallucinogens are of plant origin and the respective plants have been used as magic or sacred drugs since time immemorial. Primitive cultures, where sickness and death are usually ascribed to a supernatural cause, have long accorded hallucinogenic plants a high, even sacred, rank in their magic, medical and religious practices (Schultes, 1969). Aside from this, human beings in their persistent drive to acquire unusual states of consciousness have always used drugs. Some major hallucinatory constituents of the psychotomimetic plants are shown in Fig. 1,1. Fig. 1.1. Structures of some major hallucinogenic constituents of psychotomimetic plants 0 on 11 cEr 0„,--CP2N(5)3 o 3 Muscimole MUscarine ci130 CH2C H "2 2 0H3 O 3 Yescaline Harmine CF2CH2N(OH3)2 a) 111=H; R2=H: N,N—Dimethyltryptamine b)R I=H; R2=0H: Eufotenine c)R I=H; R2= CC 5—Nethoxy—N,11— a)R 1=H; R2=H: (+)—Lysergic acid amide dimethyltryptamine b)R I=CH0RCH3; R2=H: (-0—Lysergic acid d) RI=OH; R2=H: Psilocin met hylcarbinolamide e) RI=OPO3H; R2=H: Psilocybin a) R1=e2H5; R2=C225: (+)—LSD OH c5 HII (n) (n) CIL CH3 ZS,9—Tetrahydrocannabinol A8—Tetrahydrohydrocannabinol 8 Of the hallucinogens, 'soma' is the most ancient. According to the old Sanskrit manuscripts, the drug, used several thousand years ago in religious rites in India and Central Asia, "made one feel like a God". It is no longer known from what plant soma was obtained (De F6lice, 1936). The use of the mild hallucinogen hashish (Cannabis sativa, marihuana, Indian hemp) dates back more than 2500 years. According to Herodotus (500 B.C.), the Scythians, Who inhabited what is now the Soviet Union, threw hemp seeds on to hot stones and intoxicated themselves by inhaling the vapours (Lewin, 1924). During the course of time, hashish became widely used throughout the world. In thirteenth century Asia Minor, the hashishins were political murderers who, by ingesting hashish, would carry out murder for pay; assassin is derived from this Arabic term. The drug became very popular in France around the middle of the nine- teenth century, especially among poets and writers in Paris (Caldwell, 19(0). The interest was such that "Club des Hachichins" was formed in Faris. members of the club included people such as Gautier and Baudelaire, the latter describing his experiences with hashish in 1860 in his famous book "Les Paradis Artificiels". Today, the drug is eaten by millions, especially in Moslem areas of North Africa and the Near East. It is in India, however, that hashish assumes extraordinary religious significance. The ancient Atharva-Veda called it a "liberator of sin" and "heavenly guide" and it is still used in temples as a sacred plant (Schultes, 1969). In addition to its religious use, it is valued by the poor of India in folk medicine and as an aphrodisiac. The hallucinogenic action of hashish is mainly due to its content of tetra- hydrocannabinols (Hofmann, 1968). Amanita muscaria, also called "fly agaric", is a mushroom that grows in Europe, Asia and North America. Koryak nomads, from the Kamchatkan peninsula in northeastern Asia, discovered its hallucinogenic property and found that the voided urine after ingesting the mushroom was also hallucinogenic. Its activity in the central nervous system is probably primarily due to muscimole although other minor constituents like musearine and bufotenine may help in potentiating the effect (L'arnsworth, 1960).
Load more

Recommended publications
  • Review of Market for Octane Enhancers
    May 2000 • NREL/SR-580-28193 Review of Market for Octane Enhancers Final Report J.E. Sinor Consultants, Inc. Niwot, Colorado National Renewable Energy Laboratory 1617 Cole Boulevard Golden, Colorado 80401-3393 NREL is a U.S. Department of Energy Laboratory Operated by Midwest Research Institute • Battelle • Bechtel Contract No. DE-AC36-99-GO10337 May 2000 • NREL/SR-580-28193 Review of Market for Octane Enhancers Final Report J.E. Sinor Consultants, Inc. Niwot, Colorado NREL Technical Monitor: K. Ibsen Prepared under Subcontract No. TXE-0-29113-01 National Renewable Energy Laboratory 1617 Cole Boulevard Golden, Colorado 80401-3393 NREL is a U.S. Department of Energy Laboratory Operated by Midwest Research Institute • Battelle • Bechtel Contract No. DE-AC36-99-GO10337 NOTICE This report was prepared as an account of work sponsored by an agency of the United States government. Neither the United States government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States government or any agency thereof. Available electronically at http://www.doe.gov/bridge Available for a processing fee to U.S.
    [Show full text]
  • First Xenon-Xenon Collisions in the Lhc
    9th International Particle Accelerator Conference IPAC2018, Vancouver, BC, Canada JACoW Publishing ISBN: 978-3-95450-184-7 doi:10.18429/JACoW-IPAC2018-MOPMF039 FIRST XENON-XENON COLLISIONS IN THE LHC M. Schaumann∗, R. Alemany-Fernandez, P. Baudrenghien, T. Bohl, C. Bracco, R. Bruce, N. Fuster-Martinez, M. A. Jebramcik, J.M. Jowett, T. Mertens, D. Mirarchi, S. Redaelli, B. Salvachua, M. Solfaroli, H. Timko, J. Wenninger, CERN, Geneva, Switzerland Abstract EXECUTION OF THE RUN In 2017, the CERN accelerator complex once again demonstrated its flexibility by producing beams of a new A total of about 18 h of LHC time were taken for the Xe ion species, xenon, that were successfully injected into LHC. collision run. The schedule was designed to include set-up, On 12 October, collisions of fully stripped xenon nuclei first injection, validation and physics data taking. A further 12 h were devoted to experiments on crystal collimation, de- were recorded for the first time in the LHC√ at a centre-of- scribed elsewhere [3]. This tight schedule was only feasible mass energy per colliding nucleon pair of sNN = 5.44 TeV. Physics data taking started 9.5hafter the first injection of by drastically reducing the complexity of the set-up follow- xenon beams and lasted a total of 6h. The integrated lumi- ing the model of the p–Pb pilot run in September 2012 [4,5] nosity delivered to the four LHC experiments was sufficient when first injection, validation and physics data-taking were that new physics results can be expected soon. We provide achieved within a single fill.
    [Show full text]
  • Formation of Highly Oxygenated Organic Molecules from Aromatic Compounds
    Formation of highly oxygenated organic molecules from aromatic compounds. Ugo Molteni1, Federico Bianchi1-2, Felix Klein1, Imad El Haddad1, Carla Frege1, Michel J. Rossi1, Josef Dommen1, Urs Baltensperger1,* 5 1Laboratory of Atmospheric Chemistry, Paul Scherrer Institute, CH-5232 Villigen, Switzerland 2Department of Physics, University of Helsinki, 00014 Helsinki, Finland Correspondence to: Urs Baltensperger ([email protected]) Abstract 10 Anthropogenic volatile organic compounds (AVOC) often dominate the urban atmosphere and consist to a large degree of aromatic hydrocarbons (ArHC), such as benzene, toluene, xylenes, and trimethylbenzenes, e.g. from handling and combustion of fuels. These compounds are important precursors for the formation of secondary organic aerosol. Despite their recognized importance as atmospheric reactants, the formation of highly oxygenated molecules (HOMs) in the gas phase leading to (extremely) low volatility compounds has not been studied in the past. Here we show that oxidation of 15 aromatics with OH leads to a subsequent autoxidation chain reaction forming HOMs with an O:C ratio of up to 1.09. This is exemplified for five single-ring ArHC (benzene, toluene, o-/m-/p-xylene, mesitylene (1,3,5-trimethylbenzene) and ethylbenzene), as well as two conjugated polycyclic ArHC (naphthalene and biphenyl). We present the identified compounds, differences in the observed oxidation patterns and discuss mechanistic pathways. We report the elemental composition of the HOMs and show the differences in the oxidation patterns of these ArHCs. A potential pathway for the 20 formation of these HOMs from aromatics is presented and discussed. We hypothesize that AVOC may contribute substantially to new particle formation events that have been detected in urban areas.
    [Show full text]
  • Inline-Supplementary-Material-1.Pdf
    Appendix 1: STOPP/START criteria version 2 applied to the TRUST dataset Physiological system Criteria Criteria included Number (%) (The relevant () criteria for each participant were applied to the dataset and recorded in of Microsoft Office Excel ® (2013)) criteria included out of total criteria STOPP criteria Indication of medication A1. Any drug prescribed without an evidence-based clinical indication. X 1/3 (33.3) A2. Any drug prescribed beyond the recommended duration, where treatment duration is X well defined. A3. Any duplicate drug class prescription e.g. two concurrent NSAIDs, SSRIs, loop diuretics, ACE inhibitors, anticoagulants (optimisation of monotherapy within a single drug class should be observed prior to considering a new agent). Cardiovascular system B1. Digoxin for heart failure with preserved systolic ventricular function (no clear evidence X 7/13 (53.8) of benefit). B2. Verapamil or diltiazem with NYHA Class III or IV heart failure (may worsen heart failure). B3. Beta-blocker in combination with verapamil or diltiazem (risk of heart block). B4. Beta blocker with symptomatic bradycardia (< 50/min), type II heart block or complete heart block (risk of profound hypotension, asystole). B5. Amiodarone as first-line antiarrhythmic therapy in supraventricular tachyarrhythmias X (higher risk of side-effects than beta-blockers, digoxin, verapamil or diltiazem). B6. Loop diuretic as first-line treatment for hypertension (safer, more effective alternatives available). B7. Loop diuretic for dependent ankle oedema without clinical, biochemical evidence or radiological evidence of heart failure, liver failure, nephrotic syndrome or renal failure (leg elevation and /or compression hosiery usually more appropriate). B8. Thiazide diuretic with current significant hypokalaemia (i.e.
    [Show full text]
  • XENON X-1100 High-Intensity Pulsed Light System
    XENON X-1100 High-Intensity Pulsed Light System The low cost R&D tool for investigating the applicability of Pulsed Light for new and emerging applications. The tool that researchers, scientists and engineers have been looking for is here. An easy-to-use photonic system developed by XENON that will open new doors and lead to new discoveries. The power of Pulsed Light In virtually all disciplines of science and technology there are applications where precise delivery of energy is demanded. One less studied energy delivery mechanism is the use of high-intensity pulsed light. At present the most prevalent example of this is in the use of lasers. However, the point source, coherent and single wavelength nature of lasers, are often not suited to the majority of challenges facing many industries. In these situations, it is crucial to have a broad spectra source so as not to be restricted in choosing materials with specific absorption characteristics. Because XENON sources generate light which extends from the deep UV to IR and often with peak pulse powers measured in megawatts, the ability of these sources to perform tasks such as breaking chemical bonds, sintering, ablating or sterilizing is highly realizable. The high peak powers generated by XENON’s production level systems are possible by tightly controlling the pulse durations measured from a few microseconds to milliseconds. Until now there was no practical method of generating this intense pulsed light in a low-cost R&D tool that was safe, compact and versatile. XENON has developed a system to address this challenge based on over 50 years of exper- tise in the Pulsed Light industry.
    [Show full text]
  • PDF Download
    CURRENT THERAPEUTIC RESEARCH VOL. 56, NO. 5, MAY 1995 EFFECTS OF CEREBRAL METABOLIC ENHANCERS ON BRAIN FUNCTION IN RODENTS KOICHIRO TAKAHASHI,l MINORU YAMAMOTO,’ MASANORI SUZUKI,’ YUKIKO OZAWA,’ TAKASHI YAMAGUCHI,l HIROFUMI ANDOH, AND KOUICHI ISHIKAWA2 ‘Department of Pharmacology, Clinical Pharmacology Research Laboratory, Yamunouchi Pharmaceutical Co. Ltd., and ‘Department of Pharmacology, School of Medicine, Nihon University, Tokyo, Japan AFWI’RACT The effects of cerebral metabolic enhancers (indeloxazine, bi- femelane, idebenone, and nicergoline) on reserpine-induced hypother- mia, the immobility period in forced swimming tests, and passive avoidance learning behavior were compared with the effects of ami- triptyline in rodents. Indeloxazine, bifemelane, and amitriptyline antagonized hypothermia in mice given reserpine. Indeloxaxine and amitriptyline decreased the immobility period in mice in the forced swimming test in a dose-dependent manner. The latency of step- through in the passive avoidance test in rats was prolonged by ad- ministration of indeloxazine but shortened by administration of amitriptyline. Neither idebenone nor nicergoline displayed any phar- macologic action in these tests. The results suggest that indeloxaxine possesses an antidepressant activity similar to that of amitriptyline but differs from amitriptyline in its anticholinergic properties and its ability to ameliorate impaired brain function such as that of learning behavior. In addition, indeloxazine exhibited broader effects on brain functions than either bifemelane, idebenone, or nicergoline. INTRODUCTION Cerebral metabolic enhancers (drugs that enhance energy metabolism) including brain glucose and ATP levels such as indeloxazine,1*2 bi- femelane, 3*4idebenone?6 and nicergoline,7>8 are currently used for the treatment of patients with various psychiatric symptoms. These symptoms include reduced spontaneity and emotional disturbance in patients with cerebral vascular disease.
    [Show full text]
  • Local Product Document Pfizer Venezuela, S.A
    LOCAL PRODUCT DOCUMENT PFIZER VENEZUELA, S.A. 1. MEDICINAL PRODUCT BRAND NAME ® SERMION 2. CUALITATIVE AND CUANTITATIVE COMPOSITION Every coated tablet contains 10 and 30 mg of Nicergoline. 3. PHARMACEUTICAL FORM Coated tablets. 4. CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS 1. Cerebrovascular insufficiency of senile source. 2. Peripheral Vasodilator. 3. Treatment of Senile dementia from light to medium level of vascular type and Alzheimer. 4.2 DOSAGE 1. 30 mg/day and Cerebrovascular insufficiency of senile source. 2. 30 mg twice per day, as Peripheral Vasodilator and on treatment of Senile dementia from light to medium level of vascular type and Alzheimer. 4.3 CONTRAINDICATIONS Hypersensitivity to Nicergoline. 4.4 WARNINGS AND PRECAUTIONS Nicergoline, as other adrenergic blocking agents, may significantly reduce blood pressure (arterial hypotension) in some patients. Likewise, as other sympatholytic agents, it has been associated to different degrees of sexual impotence and libido reduction. Do not administer this product if pregnant, if pregnancy is suspected or during breast-feeding. 4.5 ADVERSE EFFECTS Drowsiness, cephalea, tiredness, constipation, pyrosis, vomiting, diarrhea, facial flushing, sexual impotence and libido reduction, uric acid and L.H increment. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacokinetics Properties A) Onset and Duration - Benign prostatic hypertrophy, intramuscular: 2 hours. - Two hours after a single 4-mg intramuscular injection, average peak and mean urinary flow rates increased by 50% and 77%, respectively. B) Drug Concentration Levels - ORAL: 1 to 1.5 hours. - Maximal blood levels are reached 1 to 1.5 hours after oral dosing. - The mean maximum plasma concentrations after daily administration of a 30-mg film-coated tablet and a 30-mg effervescent tablet solution are 88 ng/mL and 41 ng/mL, respectively).
    [Show full text]
  • Non-Antibiotics, Efflux Pumps and Drug Resistance of Gram-Negative Rods
    Polish Journal of Microbiology MINIREVIEW 2018, Vol. 67, No 2, 129–135 DOI: 10.21307/pjm-2018-017 Non-antibiotics, Efflux Pumps and Drug Resistance of Gram-negative Rods AGNIESZKA EWA LAUDY* Department of Pharmaceutical Microbiology, Medical University of Warsaw, Warsaw, Poland Submitted 24 March 2018, revised 29 March 2018, accepted 04 April 2018 Abstract Non-antibiotic medicinal products consist of drugs with diverse activity against bacteria. Many non-antibiotics demonstrate direct anti- bacterial activity against Gram-positive cocci. The activity observed against Gram-negative rods is much lower and non-antibiotics primarily from the following groups: non-steroidal anti-inflammatory drugs, cardiovascular and antidepressant medicinal products demonstrate this activity. It has been shown that the low activity of some non-antibiotics or the absence of activity against Gram-negative rods is related, among other things, to the extrusion of these compounds from bacterial cells by multi-drug resistance efflux pumps. Substrates for the resistance-nodulation-division efflux systems include the following non-antibiotics: salicylate, diclofenac, ibuprofen, mefenamic acid, naproxen, amitriptyline, alendronate sodium, nicergoline, and ticlopidine. In addition, interactions between non-antibiotics and multi-drug resistance efflux pumps have been observed. It has also been revealed that depending on the concentration, salicylate induces expression of multi-drug resistance efflux pumps in Escherichia coli, Salmonella enterica subsp. enterica serotype Typhimurium, and Burkholderia cenoce­ pacia. However, salicylate does not affect the expression of the resistance-nodulation-division efflux systems Stenotrophomonasin maltophilia and Acinetobacter baumannii. Most importantly, there were no effects of medicinal products containing some non-antibiotic active substances, except salicylate, as substrates of multi-drug resistance efflux pumps, on the induction of Gram-negative rod resistance to quinolones.
    [Show full text]
  • Pharmacology – Inhalant Anesthetics
    Pharmacology- Inhalant Anesthetics Lyon Lee DVM PhD DACVA Introduction • Maintenance of general anesthesia is primarily carried out using inhalation anesthetics, although intravenous anesthetics may be used for short procedures. • Inhalation anesthetics provide quicker changes of anesthetic depth than injectable anesthetics, and reversal of central nervous depression is more readily achieved, explaining for its popularity in prolonged anesthesia (less risk of overdosing, less accumulation and quicker recovery) (see table 1) Table 1. Comparison of inhalant and injectable anesthetics Inhalant Technique Injectable Technique Expensive Equipment Cheap (needles, syringes) Patent Airway and high O2 Not necessarily Better control of anesthetic depth Once given, suffer the consequences Ease of elimination (ventilation) Only through metabolism & Excretion Pollution No • Commonly administered inhalant anesthetics include volatile liquids such as isoflurane, halothane, sevoflurane and desflurane, and inorganic gas, nitrous oxide (N2O). Except N2O, these volatile anesthetics are chemically ‘halogenated hydrocarbons’ and all are closely related. • Physical characteristics of volatile anesthetics govern their clinical effects and practicality associated with their use. Table 2. Physical characteristics of some volatile anesthetic agents. (MAC is for man) Name partition coefficient. boiling point MAC % blood /gas oil/gas (deg=C) Nitrous oxide 0.47 1.4 -89 105 Cyclopropane 0.55 11.5 -34 9.2 Halothane 2.4 220 50.2 0.75 Methoxyflurane 11.0 950 104.7 0.2 Enflurane 1.9 98 56.5 1.68 Isoflurane 1.4 97 48.5 1.15 Sevoflurane 0.6 53 58.5 2.5 Desflurane 0.42 18.7 25 5.72 Diethyl ether 12 65 34.6 1.92 Chloroform 8 400 61.2 0.77 Trichloroethylene 9 714 86.7 0.23 • The volatile anesthetics are administered as vapors after their evaporization in devices known as vaporizers.
    [Show full text]
  • 4 Supplementary File
    Supplemental Material for High-throughput screening discovers anti-fibrotic properties of Haloperidol by hindering myofibroblast activation Michael Rehman1, Simone Vodret1, Luca Braga2, Corrado Guarnaccia3, Fulvio Celsi4, Giulia Rossetti5, Valentina Martinelli2, Tiziana Battini1, Carlin Long2, Kristina Vukusic1, Tea Kocijan1, Chiara Collesi2,6, Nadja Ring1, Natasa Skoko3, Mauro Giacca2,6, Giannino Del Sal7,8, Marco Confalonieri6, Marcello Raspa9, Alessandro Marcello10, Michael P. Myers11, Sergio Crovella3, Paolo Carloni5, Serena Zacchigna1,6 1Cardiovascular Biology, 2Molecular Medicine, 3Biotechnology Development, 10Molecular Virology, and 11Protein Networks Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 34149, Trieste, Italy 4Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy 5Computational Biomedicine Section, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany 6Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy 7National Laboratory CIB, Area Science Park Padriciano, Trieste, 34149, Italy 8Department of Life Sciences, University of Trieste, Trieste, 34127, Italy 9Consiglio Nazionale delle Ricerche (IBCN), CNR-Campus International Development (EMMA- INFRAFRONTIER-IMPC), Rome, Italy This PDF file includes: Supplementary Methods Supplementary References Supplementary Figures with legends 1 – 18 Supplementary Tables with legends 1 – 5 Supplementary Movie legends 1, 2 Supplementary Methods Cell culture Primary murine fibroblasts were isolated from skin, lung, kidney and hearts of adult CD1, C57BL/6 or aSMA-RFP/COLL-EGFP mice (1) by mechanical and enzymatic tissue digestion. Briefly, tissue was chopped in small chunks that were digested using a mixture of enzymes (Miltenyi Biotec, 130- 098-305) for 1 hour at 37°C with mechanical dissociation followed by filtration through a 70 µm cell strainer and centrifugation.
    [Show full text]
  • 11.8 Aromatic Compounds Aromatic Compounds Naming Aromatic
    11.8 Aromatic Compounds In 1825, Michael Faraday isolated a hydrocarbon called benzene, which consists of a six-carbon ring with alternating double bonds and has the molecular formula C6H6. Learning Goal Describe the bonding in benzene; name aromatic compounds, and draw their skeletal formulas. Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. Aromatic Compounds Benzene is • an aromatic compound • a ring of six C atoms, each bonded to one H atom • a flat ring structure drawn with three alternating double bonds • represented by two structures because the electrons are shared equally among all the C atoms • represented by a skeletal formula using a circle in the center instead of the alternating double bonds Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. Naming Aromatic Compounds Aromatic compounds containing a benzene ring and a single substituent are named as benzene derivatives. Since the ring contains only one substituent, the ring is not numbered. Some common names such as toluene, aniline, and phenol are allowed by IUPAC rules. Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. 1 Naming Aromatic Compounds When there are two or more substituents, the benzene ring is numbered to give the lowest numbers to the substituents. Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. Naming Aromatic Compounds When a common name such as toluene, phenol, or aniline can be used, • the carbon atom attached to the methyl, hydroxyl, or amine group is numbered as carbon 1 • the other substituents are named alphabetically Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc.
    [Show full text]
  • Xenon Gas Xe Safety Data Sheet SDS P4677
    Xenon Safety Data Sheet P-4677 This SDS conforms to U.S. Code of Federal Regulations 29 CFR 1910.1200, Hazard Communication. Date of issue: 01/01/1979 Revision date: 10/24/2016 Supersedes: 10/02/2014 SECTION: 1. Product and company identification 1.1. Product identifier Product form : Substance Name : Xenon CAS No : 7440-63-3 Formula : Xe Other means of identification : Xenon 1.2. Relevant identified uses of the substance or mixture and uses advised against Use of the substance/mixture : Industrial use. Use as directed. 1.3. Details of the supplier of the safety data sheet Praxair, Inc. 10 Riverview Drive Danbury, CT 06810-6268 - USA T 1-800-772-9247 (1-800-PRAXAIR) - F 1-716-879-2146 www.praxair.com 1.4. Emergency telephone number Emergency number : Onsite Emergency: 1-800-645-4633 CHEMTREC, 24hr/day 7days/week — Within USA: 1-800-424-9300, Outside USA: 001-703-527-3887 (collect calls accepted, Contract 17729) SECTION 2: Hazard identification 2.1. Classification of the substance or mixture GHS-US classification Compressed gas H280 2.2. Label elements GHS-US labeling Hazard pictograms (GHS-US) : GHS04 Signal word (GHS-US) : WARNING Hazard statements (GHS-US) : H280 - CONTAINS GAS UNDER PRESSURE; MAY EXPLODE IF HEATED OSHA-H01 - MAY DISPLACE OXYGEN AND CAUSE RAPID SUFFOCATION Precautionary statements (GHS-US) : P202 - Do not handle until all safety precautions have been read and understood P271+P403 - Use and store only outdoors or in a well-ventilated place CGA-PG05 - Use a back flow preventive device in the piping CGA-PG10 - Use only with equipment rated for cylinder pressure CGA-PG06 - Close valve after each use and when empty CGA-PG02 - Protect from sunlight when ambient temperature exceeds 52°C (125°F) 2.3.
    [Show full text]