DOCSLIB.ORG

A Study on Beta Blockers - a Brief Review Tv

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Study on Beta Blockers - a Brief Review Tv IJRPC 2018, 8(4), 508-529 Namratha et al. ISSN: 22312781 INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Review Article A STUDY ON BETA BLOCKERS - A BRIEF REVIEW TV. Namratha*, KC. Chaluvaraju and AM. Anushree Department of Pharmaceutical Chemistry, Government College of Pharmacy, Bengaluru-560 027, Karnataka, India. ABSTRACT Beta blockers are agents or drugs which competitively inhibit the action of catecholamines at the beta adrenergic receptors, which are mainly used to treat variety of clinical conditions like angina, hypertension, asthma, COPD and arrhythmias. These drugs are also useful in several other therapeutic situations including shock, premature labor and opioid withdrawal, and as adjuncts to general anesthetics. These drugs produce their effect by interacting with the beta adrenergic receptors. In the present communication, an effort has been made to compile beta adrenergic receptors and the chemistry, discovery and development, classification and therapeutic applications of beta blockers. Keywords: Beta blockers, adrenergic receptors, catecholamines and aryloxypropanolamines. 1. INTRODUCTION Beta blockers were first developed by Sir 1.1 Adrenergic receptors James Black in 1962. The structures of The ability of a molecule to selectively these receptors have been studied by x- agonize or antagonize adrenergic ray crystallography.5 In the current article receptor made great advances in beta blockers are majorly focused with pharmacotherapeutics. The discovery of respect to their location, functions adrenergic receptors lead to major mediated, discovery and development, development of newer adrenergic SAR, classification, structures and agonists as well as antagonist.1 therapeutic applications. Adrenergic receptors are 7- transmembrane spanning receptors 1.2 Locations and agonistic action of beta which mediate both central and adrenergic receptors6 peripheral actions of the adrenergic The following are the various beta neurotransmitters. Adrenergic receptors adrenergic receptors found in different are found in nearly all peripheral tissues physiological locations and their actions and on many neurons within the central mediated by their stimulation with beta nervous system.2 They play an important adrenergic agonists. (Table 1) role in the control of blood pressure, myocardial contractile rate and force, 2. DISCOVERY AND DEVELOPMENT OF airway reactivity, and a variety of BETA ADRENERGIC ANTAGONISTS metabolic and central nervous system One of the beta adrenergic agonist functions.3 drugs, Isoprenaline (Fig. 1), was In 1948, Raymond P. Ahlquist classified considered as a lead molecule. It is a the adrenergic receptors into two major beta receptor agonist but has no action types i.e. α and β, based on their on alpha receptors. This lead molecule pharmacological characteristics such as was studied in depth and suitable rank order of potency of agonists.4 structural modifications required for beta Subsequently, both α and β types were adrenergic antagonistic activity were 3 subdivided into α1, α2, β1, β2 and implemented. β3subtypes respectively. Further, based The first such modifications carried out on pharmacological and molecular included was the replacement of the evidences alpha receptor subtypes were phenolic hydroxyl groups in isoprenaline classified into α1A, α1B, α1D. with chloro substituents gave 508 IJRPC 2018, 8(4), 508-529 Namratha et al. ISSN: 22312781 dichloroisoprenaline (Fig. 2), which is a 3.2 Based on their chemical nucleus partial agonist. Beta blockers can be classified This promising molecule into: dichloroisoprenaline gave an insight in 1. Arylethanolamines next stage of development to convert the Ex: pronetalol, sotalol, labetalol, beta adrenergic agonistic activity into brefonalol, Bufuralol antagonistic activity. The general 2. Aryloxypropanolamines methodology to do so was to introduce Ex: Propranolol, esmolol, metoprolol, another aromatic ring into the existing acebutalol, atenolol molecule. This resulted in a drastic change in hydrophobic interaction of the molecule with the receptor and also 3.3 FDA classes of beta blockers for changed the induced fit between the use in pregnant women 7,8 ligand and the binding site. This new fit A. Category A resulted in binding of ligand to the Adequate and well-controlled studies receptor’s binding site but without the have failed to demonstrate a risk to activation of the same. the fetus in the first trimester of Considering the above fact, the chloro pregnancy (and there is no evidence groups were replaced with a benzene of risk in later trimesters). ring, to form a rigid naphthalene ring No β-blockers is completely safe for system. This gave pronethalol (Fig. 3), using during pregnancy. the first beta blocker to be used clinically to treat angina, arrhythmia and B. Category B hypertension.5 Though, it exhibited great Animal reproduction studies have therapeutic activity, it was soon failed to demonstrate a risk to the withdrawn due to its carcinogenic effects. fetus and there are no adequate and 6 well-controlled studies in pregnant The further development was a result of women. the introduction of side chains between Eg. Pindalol, acebutalol, sotalol the naphthalene ring and the ethanolamine. The discovery of C. Category C propranolol (Fig. 4) was in fact a result of Animal reproduction studies have an accident during the synthesis for shown an adverse effect on the fetus which α-naphthol was used in the and there are no adequate and well reaction mixture instead of the β- controlled studies in humans, but naphthol and a drug having structure potential benefits may warrant use of with side chain at C1 of the naphthalene the drug in pregnant women despite ring rather than the C2 was obtained. potential risks. Propranolol is a pure antagonist and this Eg. Labetalol, Bisoprolol, Timolol, molecule is considered to be a bench Metoprolol mark in evaluation of all other beta blockers. D. Category D There is positive evidence of human 3. CLASSIFICATION OF BETA fetal risk based on adverse reaction BLOCKERS data from investigational or marketing 3.1 Beta blocking agents are classified experience or studies in humans, but into 3 classes based on selectivity and potential benefits may warrant use of action: the drug in pregnant women despite 1 First generation-Non selective in potential risks. nature and cause no vasodilation Eg. Atenolol Ex: Propranolol, Nadolol, Pindolol 2 Second generation - cardioselective 4. STRUCTURE ACTIVITY in nature RELATIONSHIP OF Ex: Acebutolol, atenolol ARYLOXYPROPANOLAMINES 3 Third generation–Non selective Presently, aryloxypropanolamines are agents which cause vasodilation the most commonly used beta Ex: Primidolol, Epanolol adrenergic blockers. Though the beta blockers are marketed in the racemic form, typically the activity lies only in one of its isomeric form. In arylethanolamines, the activity was 509 IJRPC 2018, 8(4), 508-529 Namratha et al. ISSN: 22312781 found to reside in the (R) form, while receptors by the neurotransmitters, in case of aryloxypropanolamines, it results in the production of cAMP by resides in the (S) form.9 adenyl cyclase. cAMP is a secondary Following are the necessary structural messenger molecule which activates requirements for their optimum activity: 4 the Protein Kinase A (PKA). The Presence of branched N-alkyl action of PKA is to increase the functional moieties. This fits into the calcium release which is responsible hydrophobic pockets, both branching for the physiological action. Beta and extension of this alkyl side chain blockers act by binding to the beta is essential. adrenergic receptors and blocking the Presence of hydroxyl group on the action of neurotransmitters. (Fig. 5) side chain is essential for the hydrogen bonding with receptors. 6. BETA ADRENERGIC Presence of amino group is essential BLOCKERS10-25 and it should be secondary in nature, Various beta adrenergic blockers, and it is required for the ionic bonding their structures, molecular formula, interaction. molar mass and therapeutic uses are Presence of oxymethylene bridge is discussed here. also essential for the drug to bind to The following are the most widely the receptor. used beta adrenergic blockers: (Table 2). However, the following changes are feasible: The aromatic ring system can be 7. CONCLUSION heterocyclic in nature. Beta blockers constitute an important Aryloxy substitution can be at C2 class of drugs in the clinical treatment which gives more potent compounds of various disorders like hypertension, than those substituted at C1 angina pectoris, asthma, glaucoma Variation in lipophilicity can be and arrhythmias. Various physical achieved by introducing suitable and chemical parameters of beta substituents. adrenergic antagonists such as the specificity, solubility, permeability and The following modifications were found to be distribution of the molecule can be detrimental and lead to loss of activity: modified in order to obtain a drug with Introduction of substituent on the preferred characteristics. Study of the propyl side chain. nature and type of receptor at the Replacement of the ethereal oxygen target tissue, and also by analyzing with S, CH2 or N-CH3. the structure activity relationship helps in obtaining molecules with 5. MECHANISM OF ACTION OF BETA optimum biological and BLOCKERS 6 physiochemical properties. Beta receptors are G protein coupled receptors. Activation of these 510 IJRPC 2018, 8(4), 508-529 Namratha et al. ISSN: 22312781 TABLES Table
Load more

Recommended publications
  • UC San Francisco Electronic Theses and Dissertations
    UCSF UC San Francisco Electronic Theses and Dissertations Title Machine Learning for Medical Image Analysis and Compound-Target Interactions Permalink https://escholarship.org/uc/item/8c54b5m7 Author Gaskins, Garrett Publication Date 2020 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California Machine Learning for Medical Image Analysis and Compound-Target Interactions by Garrett Gaskins DISSERTATION Submitted in partial satisfaction of the requirements for degree of DOCTOR OF PHILOSOPHY in Biological and Medical Informatics in the GRADUATE DIVISION of the UNIVERSITY OF CALIFORNIA, SAN FRANCISCO Approved: ______________________________________________________________________________Michael J Keiser Chair ______________________________________________________________________________Jason Gestwicki ______________________________________________________________________________Sourav Bandyopadhyay ______________________________________________________________________________ ______________________________________________________________________________ Committee Members Copyright 2020 by Garrett Gaskins ii ACKNOWLEDGEMENTS The graduate process is quite an experience. There is a subtle difficulty in describing it, as a peculiar quality of its existence is defined by the uniqueness of it all. Everyone I’ve known to be a part of or to have gone through graduate school has described a truly different journey. Perhaps this is integral to what makes the whole thing work. At the least,
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al
    USOO9498481 B2 (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao et al. (45) Date of Patent: *Nov. 22, 2016 (54) CYCLOPROPYL MODULATORS OF P2Y12 WO WO95/26325 10, 1995 RECEPTOR WO WO99/O5142 2, 1999 WO WOOO/34283 6, 2000 WO WO O1/92262 12/2001 (71) Applicant: Apharaceuticals. Inc., La WO WO O1/922.63 12/2001 olla, CA (US) WO WO 2011/O17108 2, 2011 (72) Inventors: Tadimeti Rao, San Diego, CA (US); Chengzhi Zhang, San Diego, CA (US) OTHER PUBLICATIONS Drugs of the Future 32(10), 845-853 (2007).* (73) Assignee: Auspex Pharmaceuticals, Inc., LaJolla, Tantry et al. in Expert Opin. Invest. Drugs (2007) 16(2):225-229.* CA (US) Wallentin et al. in the New England Journal of Medicine, 361 (11), 1045-1057 (2009).* (*) Notice: Subject to any disclaimer, the term of this Husted et al. in The European Heart Journal 27, 1038-1047 (2006).* patent is extended or adjusted under 35 Auspex in www.businesswire.com/news/home/20081023005201/ U.S.C. 154(b) by Od en/Auspex-Pharmaceuticals-Announces-Positive-Results-Clinical M YW- (b) by ayS. Study (published: Oct. 23, 2008).* This patent is Subject to a terminal dis- Concert In www.concertpharma. com/news/ claimer ConcertPresentsPreclinicalResultsNAMS.htm (published: Sep. 25. 2008).* Concert2 in Expert Rev. Anti Infect. Ther. 6(6), 782 (2008).* (21) Appl. No.: 14/977,056 Springthorpe et al. in Bioorganic & Medicinal Chemistry Letters 17. 6013-6018 (2007).* (22) Filed: Dec. 21, 2015 Leis et al. in Current Organic Chemistry 2, 131-144 (1998).* Angiolillo et al., Pharmacology of emerging novel platelet inhibi (65) Prior Publication Data tors, American Heart Journal, 2008, 156(2) Supp.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • 2D6 Substrates 2D6 Inhibitors 2D6 Inducers
    Physician Guidelines: Drugs Metabolized by Cytochrome P450’s 1 2D6 Substrates Acetaminophen Captopril Dextroamphetamine Fluphenazine Methoxyphenamine Paroxetine Tacrine Ajmaline Carteolol Dextromethorphan Fluvoxamine Metoclopramide Perhexiline Tamoxifen Alprenolol Carvedilol Diazinon Galantamine Metoprolol Perphenazine Tamsulosin Amiflamine Cevimeline Dihydrocodeine Guanoxan Mexiletine Phenacetin Thioridazine Amitriptyline Chloropromazine Diltiazem Haloperidol Mianserin Phenformin Timolol Amphetamine Chlorpheniramine Diprafenone Hydrocodone Minaprine Procainamide Tolterodine Amprenavir Chlorpyrifos Dolasetron Ibogaine Mirtazapine Promethazine Tradodone Aprindine Cinnarizine Donepezil Iloperidone Nefazodone Propafenone Tramadol Aripiprazole Citalopram Doxepin Imipramine Nifedipine Propranolol Trimipramine Atomoxetine Clomipramine Encainide Indoramin Nisoldipine Quanoxan Tropisetron Benztropine Clozapine Ethylmorphine Lidocaine Norcodeine Quetiapine Venlafaxine Bisoprolol Codeine Ezlopitant Loratidine Nortriptyline Ranitidine Verapamil Brofaramine Debrisoquine Flecainide Maprotline olanzapine Remoxipride Zotepine Bufuralol Delavirdine Flunarizine Mequitazine Ondansetron Risperidone Zuclopenthixol Bunitrolol Desipramine Fluoxetine Methadone Oxycodone Sertraline Butylamphetamine Dexfenfluramine Fluperlapine Methamphetamine Parathion Sparteine 2D6 Inhibitors Ajmaline Chlorpromazine Diphenhydramine Indinavir Mibefradil Pimozide Terfenadine Amiodarone Cimetidine Doxorubicin Lasoprazole Moclobemide Quinidine Thioridazine Amitriptyline Cisapride
    [Show full text]
  • NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Amphetamine and Methamphetamine
    Published 2005 Wiley-Liss, Inc.w Birth Defects Research (Part B) 74:471–584 (2005) NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity Of Amphetamine and Methamphetamine Mari Golub,1 Lucio Costa,2 Kevin Crofton,3 Deborah Frank,4 Peter Fried,5 Beth Gladen6 Rogene Henderson,7 Erica Liebelt,8 Shari Lusskin,9 Sue Marty,10 Andrew Rowland11 John Scialli12 and Mary Vore13 1California Environment Protection Agency, Sacramento, California 2University of Washington, Seattle, Washington 3U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 4Boston Medical Center, Boston, Massachusetts 5Carleton University, Ottawa, Ontario 6National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 7Lovelace Respiratory Research Institute, Albuquerque, New Mexico 8University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 9New York University School of Medicine, New York, New York 10The Dow Chemical Company, Midland, Michigan 11University of New Mexico, Albuquerque, New Mexico 12Phoenix, Arizona 13University of Kentucky, Lexington, Kentucky PREFACE studies indexed before December 31, 2004. References were also identified from databases such as REPRO- The National Toxicology Program (NTP) and the TOXs, HSDB, IRIS, and DART and from report National Institute of Environmental Health Sciences bibliographies. (NIEHS) established the NTP Center for the Evaluation This evaluation resulted from the efforts of a 13- of Risks to Human Reproduction (CERHR) in June 1998. member panel of government and non-government The purpose of the Center is to provide timely, unbiased, scientists that culminated in a public expert panel scientifically sound evaluations of human and experi- meeting held January 10–12, 2005. This report is a mental evidence for adverse effects on reproduction and product of the Expert Panel and is intended to (1) development caused by agents to which humans may be interpret the strength of scientific evidence that exposed.
    [Show full text]
  • Properties and Units in Clinical Pharmacology and Toxicology
    Pure Appl. Chem., Vol. 72, No. 3, pp. 479–552, 2000. © 2000 IUPAC INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY AND LABORATORY MEDICINE SCIENTIFIC DIVISION COMMITTEE ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)# and INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY CHEMISTRY AND HUMAN HEALTH DIVISION CLINICAL CHEMISTRY SECTION COMMISSION ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)§ PROPERTIES AND UNITS IN THE CLINICAL LABORATORY SCIENCES PART XII. PROPERTIES AND UNITS IN CLINICAL PHARMACOLOGY AND TOXICOLOGY (Technical Report) (IFCC–IUPAC 1999) Prepared for publication by HENRIK OLESEN1, DAVID COWAN2, RAFAEL DE LA TORRE3 , IVAN BRUUNSHUUS1, MORTEN ROHDE1, and DESMOND KENNY4 1Office of Laboratory Informatics, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; 2Drug Control Centre, London University, King’s College, London, UK; 3IMIM, Dr. Aiguader 80, Barcelona, Spain; 4Dept. of Clinical Biochemistry, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland #§The combined Memberships of the Committee and the Commission (C-NPU) during the preparation of this report (1994–1996) were as follows: Chairman: H. Olesen (Denmark, 1989–1995); D. Kenny (Ireland, 1996); Members: X. Fuentes-Arderiu (Spain, 1991–1997); J. G. Hill (Canada, 1987–1997); D. Kenny (Ireland, 1994–1997); H. Olesen (Denmark, 1985–1995); P. L. Storring (UK, 1989–1995); P. Soares de Araujo (Brazil, 1994–1997); R. Dybkær (Denmark, 1996–1997); C. McDonald (USA, 1996–1997). Please forward comments to: H. Olesen, Office of Laboratory Informatics 76-6-1, Copenhagen University Hospital (Rigshospitalet), 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. E-mail: [email protected] Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted without the need for formal IUPAC permission on condition that an acknowledgment, with full reference to the source, along with use of the copyright symbol ©, the name IUPAC, and the year of publication, are prominently visible.
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Subject Index
    Subject Index A-64662 497 classification 11-14 AA-861 511 (fig) function 111-114 acebutolol 69,70 hemodynamic effects 110-121 brand names 868 (table) in hypertensive disease 114 dosage 83 (table), 860 (table) mechanism of action 110-121 intrinsic sympathomimetic activity 82 metabolism 108-110 pharmacological profile 83 (table) pharmacodynamics 110-121 see also diuretics 83 pharmacokinetics 108-110 acetazolamide 22, 24 sUbtypes 111,241-246 chemical structure 23 (fig), 24 (table) a2- 246 duration of action 39 (table) classification at central cardiovascular fractional sodium excretion 30 (table) sites 242-244 metabolism 37 definition at peripheral sites onset of action 39 (table) 241-242 peak of action 39 (table) a-adrenoceptor agonists 113 (table) pKa 37 (table) a-adrenoceptor antagonists 15, 105-125 plasma elimination half-life 37 antihypertensive activity 114-119 protein binding 37 (table) chemistry 106-108 renal site/mechanism of action 26, 30 combination with other drugs 123 (table) contraindications 123-124 site of action 29 differential antagonism 242 teratogenesis 800,800-802 dosage 121-123 tubular fluid/plasma-sodium drug interactions 123 concentrations ratio 30 (fig) effects on: c10nidine 240-241 see also diuretics guanfacine 240-241 acetylcholine 316 a-methyldopa 240-241 acetylsalicylic acid 53 hemodynamic profile 119-120 Actinomycetales extracts/compounds side effects 124 728 therapeutic use 121-123 adenosine-3, 5-cyclic monophosphate toxicity 124 (cAMP) 73 ~-adrenoceptor antagonists 66-67, 815 adenosine triphosphate 73,268 a-adrenoceptor
    [Show full text]
  • 33-Adrenoceptor-Mediated Relaxation Induced by Isoprenaline And
    J. Smooth Muscle Res. 33 : 99-106. 99 The )32 and [33-Adrenoceptor-Mediated Relaxation Induced by Isoprenaline and Salbutamol in Guinea Pig Taenia Caecum Katsuo KOIKE, Tsukasa IcHiNo, Takahiro HORINOUCHI and Issei TAKAYANAGI Departmentof Chemical Pharmacology, Toho University School of PharmaceuticalSciences, 2-2-1, Miyama,Funabashi, Chiba 274, Japan Abstract To understand the receptor subtypes responsible for /3adrenoceptormediated relaxa tion of guinea pig taenia caecum, we investigated the effects of isoprenaline and salbutamol . Isoprenaline and salbutamol caused dose-dependent relaxation of the guinea pig taenia caecum. Propranolol, bupranolol and butoxamine produced shifts of the concentration response curves for isoprenaline and salbutamol. Schild regression analyses carried out for propranolol against isoprenaline and salbutamol gave pA2 values of 8.43 and 8.88, respective ly. Schild regression analyses carried out for butoxamine against isoprenaline and sal butamol gave pA2 values of 6.46 and 6.68, respectively. Schild regression analyses carried out for bupranolol against isoprenaline and salbutamol gave pA2 values of 8.60 and 8.69, respectively. However, in the presence of 3 x 10' M atenolol, 10-4 M butoxamine and 10-6 M phentolamine to block the fir , /32 and a -adrenoceptor effects, respectively, Schild regression analyses carried out for bupranolol against isoprenaline and salbutamol gave pA2 values of 5.77 and 5.97, respectively. These results suggest that the relaxant responses to isoprenaline and salbutamol in the guinea pig taenia caecum are mediated by both the /.32 and the A-adrenoceptors. Key words : f2-adrenoceptor, A-adrenoceptor, isoprenaline, salbutamol , guinea pig taenia caecum Introduction The /3adrenoceptors were subclassified as and /32subtypes based on the agonist potency and tissue localization.
    [Show full text]
  • Autonomic Nervous System Final.Pdf
    University of Hawai‘i Hilo Pre- Nursing Program NURS 203 – General AUTONOMIC NERVOUS SYSTEM Pharmacology Danita Narciso Pharm D 1 LEARNING OBJECTIVES Understand the basic function of the autonomic nervous system (ANS) Know the neurotransmitters and receptors of each branch of the autonomic nervous system Understand if a tissue or organ is being activated by a certain branch of the ANS what the resulting action would be Understand how these two systems work in concert for daily living and situation of fight or flight 2 AUTONOMIC NERVOUS SYSTEM – WHERE IT FITS IN Nervous System Central Peripheral Somatic Autonomic (Skeletal Muscle) Parasympathetic Sympathetic Brain (cholinergic) ACh (adrenergic) NE Spinal Cord Nicotinic Alpha Beta α1, α2 β1, β2 Muscarinic 3 AUTONOMIC NERVOUS SYSTEM Fight or Flight Adrenergic Rest & Digest Norepinephrine Cholinergic Acetylcholine 4 AUTONOMIC NERVOUS SYSTEM – WHERE IT FITS IN Nervous System Central Peripheral Somatic Autonomic (Skeletal Muscle) Parasympathetic Sympathetic Brain (cholinergic) ACh (adrenergic) NE Spinal Cord Nicotinic Alpha Beta α1, α2 β1, β2 Muscarinic 5 AUTONOMIC NERVOUS SYSTEM (ANS) Parasympathetic NS Nicotinic Muscarinic Peripheral Sympathetic NS Alpha Autonomic Beta Nerves Parasympathetic Sympathetic Carrying ACh (cholinergic) ACh (adrenergic) NE Cholinergic Carrying NE Nicotinic Beta Adrenergic Alpha α1, α2 β1, β2 Muscarinic 6 AUTONOMIC NERVOUS SYSTEM (ANS) 7 AUTONOMIC NERVOUS SYSTEM (ANS) Ganglion: Group of nerve cell bodies. Connects pre and post ganglionic nerves. 8 AUTONOMIC NERVOUS SYSTEM (ANS) 9 AUTONOMIC NERVOUS SYSTEM (ANS) 10 AUTONOMIC NERVOUS SYSTEM (ANS) Preganglionic PNS ACh Preganglionic SNS ACh Post ganglionic Post ganglionic PNS SNS ACh NE 11 ACTIONS OF THE ANS - SNS Think fight or flight Dilate pupils Let in more light to see the bear Inhibit salivation This is no time to be hungry Relax airways Increase O2 intake Increase heart rate ….
    [Show full text]
  • Guidance for the Format and Content of the Protocol of Non-Interventional
    PASS information Title Metformin use in renal impairment Protocol version identifier Version 2 Date of last version of 30 October 2013 protocol EU PAS register number Study not registered Active substance A10BA02 metformin Medicinal product Metformin Product reference N/A Procedure number N/A Marketing authorisation 1A Farma, Actavis, Aurobindo, Biochemie, Bluefish, holder(s) Hexal, Mylan, Orifarm, Pfizer, Sandoz, Stada, Teva Joint PASS No Research question and To assess the use and safety of metformin in patients objectives with and without renal insufficiency in current clinical practice in at least two EU Member States. Country(-ies) of study Denmark, United Kingdom Author Christian Fynbo Christiansen, MD, PhD Page 1/214 Marketing authorisation holder(s) Marketing authorisation N/A holder(s) MAH contact person N/A Page 2/214 1. Table of Contents PASS information .......................................................................................................... 1 Marketing authorisation holder(s) .................................................................................... 2 1. Table of Contents ...................................................................................................... 3 2. List of abbreviations ................................................................................................... 4 3. Responsible parties .................................................................................................... 5 4. Abstract ..................................................................................................................
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
    USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO).
    [Show full text]