Journal of Pharmacy and Pharmacology 1969 Volume.21 No.8

Total Page:16

File Type:pdf, Size:1020Kb

Journal of Pharmacy and Pharmacology 1969 Volume.21 No.8 The Pharmaceutical Society of Great Britain P a l m e r lop nome for physiology and pharmacology apparatus Known and used in physiology and pharmacology laboratories all over the world, C. F. Palmer equipment has a long-standing reputation for quality, reliability and precision. New products are continually under development, and as a member of the Baird &Tatlock Group, C. F. Palmer have extensive research and development facilities at their disposal. Palmer equipment is now available on improved deliveries. For a revised delivery schedule, or to order your new catalogue, write to the address below. Palmer kymographs such as this are in service in labora- Continuous injector. This unit, which can be used with all sizes of record-type tories all over the world, providing smoked paper records syringes, automatically controls injection rates. A range of motor speeds is of muscle and tissue movement, or through a manometer, available giving emptying rates of 10 mins, to 480 rrins. per inch, of blood pressure. A 6-gear motor gives paper speeds from Square-Wave Stim ulator. Pro vines a square-wave output of independently •1mm to 10mm per second. A.C. time-clock and s gnal variable pulse r?te (1/20-100 p.p.s.), ou1*«. width (10 microsec. to 103 millisec.) markers, and the Starling ventilation pump are fitted. end :nt«nsKy. Fuise rate is controKaM* ether in steps or continuously. C. F. Palmer (London) Lt«5. <2/1$ C-neKsie Hu., Tne Hyde, Colindale, London, IM.W.9 Telephone: 01 -205 5432 Member cf '.he Baird & Tatlock Division of Tarmac Derby Limited C P .1 /C Journal of Pharmacy and Pharmacology Published by T h e P harmaceutical S o c ie t y o f G r e a t B r i t a i n 17 Bloomsbury Square, London, W.C.l. Telephone: 01-405 8967 Volume 21 Number 8 August 1969 Editor: George Brownlee, D.Sc., Ph.D., F.P.S. Assistant Editor: J. R. Fowler, B.Pharm., F.P.S Editorial Board: H. S. Bean, W. C. Bowman, H. Burlinson, J. E. Carless, F. Fish. G. E. Foster, F. Hartley, E. F. Hersant, C. A. Johnson, K. A. Lees, A. D. Macdonald, A. McCoubrey, D. W. Mathieson, M. J. Rand, G. F. Somers, J. B. Stenlake, G. B. West, R. T. Williams, Secretary. D. F. Lewis. Notice to Contributors T ables (for each copy of the text) should be typed on separate sheets, their headings should T h e J o u r n a l o f P h a r m a c y a n d P h a r m a ­ describe their content and they should be c o l o g y reviews and reports original research in understandable without reference to the text. those sciences which contribute to the develop­ They should not be ruled. ment and evaluation of medicinal substances, covering inter alia biochemistry, chemistry, Illustrations. Should be kept to the mini­ microbiology, pharmaceutics, pharmacognosy mum number necessary to the proper under­ and pharmacology. Short papers of immediate standing of the subject matter. Two of each interest are published as ‘Letters to the Editor.’ are required, one prepared as described below the other a photo copy suitable for submission Original research papers or review articles are to a referee. Line illustrations such as graphs accepted on the understanding that they are sub­ or apparatus diagrams should be clearly and ject to editorial revision and that their content boldly drawn in Indian ink on tracing cloth or has not been published in whole or in part paper, white paper, faintly blue-lined graph elsewhere. paper or Bristol board. The initial dimensions should be chosen to allow for a reduction to at Text. Authors should consult a c u r r e n t least one-half and not more than one-quarter of issue of the Journal and conform to the typo­ the original size. (Most illustrations in the graphical conventions, use of headings, lay-out Journal are 2-4 inches, in width.) Kymograph of tables, and citation of references. Texts records and photographs should be selected to must be typewritten in double spacing on sheets allow for reduction to a similar extent. Letter­ not larger than 9 13 inches (22 32 cm) x x ing and numbering should be inserted lightly with a li inch (3 cm) margin. The top copy and clearly in pencil. Curves based on experi­ and one carbon copy should be sent. The mental data should carry clear and bold name(s) of the contributor(s), the name and indications of the experimentally determined address of the laboratory where the work was points, which should be marked by using, done, and a shortened title (not more than a preferably, circles, crosses, triangles or squares. total of 50 letters and spaces) should accom­ Legends for illustrations should be typed on pany the typescript. The presentation adopted separate sheets of paper and appended to the should be that best suited to the clear exposition typescript of the paper or to the individual of the subject matter. A summary should be figures. The author’s name, the title of the included, giving results and conclusions in the paper and the number of the figure should be form of an abstract suitable for use as such by written lightly in pencil on the back of each abstracting journals. illustration. The approximate position of each illustration should be marked in the text. References. References s iould be arranged to the h a r v a r d system. In the text the R eprints. 50 reprints are supplied free of surname of the author(s) and the date of charge to the author. A further 10 reprints publication are given thus: Lewis & Train are supplied free to each co-author. Additional (1965) described . .. or ___ has been described reprints may be purchased. (Lewis & Train, 1965). The list of references is in alphabetical order of first authors and each Copyright reference is arranged as follows: L e w is , C. J. & T r a i n , D. (1965). J. Pharm. Pharmac., 17, © 1969 by the Journal of Pharmacy and 33-41. The title of publication is underlined Pharmacology. All rights of reproduction are and abbreviated as in World List of Scientific reserved in all countries in respect of all articles, Periodicals (4th edn, 1963-1965 and supple­ papers, illustrations, etc. ments) and is followed by the volume number and first and last page numbers. References to Annual subscription (including postage) £9, books should be as follows: G o o d m a n , L. S. & (LJ.S.A. $25). Single copies £1, (U.S.A. $3). G i l m a n , A. (1965). The Pharmacological Basis of Therapeutics, 3rd edn, p. 464, London: Claims for missing copies cannot be considered Collier-Macmillan. unless received within 3 months of publication. iv Journal of Pharmacy and Pharmacology August, 1969 d e l i v e r e d to your bench q u i c k l y Hundreds of different products in the complete Difco range are kept in stock ready to be on your bench without delay. We shall always be pleased to obtain other items specially to order. Speed, convenience, reliability . and remember that Difco offer the only c o m p le te line of culture media available in U.K. Please send for the latest literature concerning your special interests. la b o r a t o r y s e r v i c e BAIRD & TATLOCK (LONDON) LTD., CHADWELL HEATH, ESSEX, ENGLAND. Branches in London, Manchester, Birmingham and Glasgow. Member of Tarmac Derby Ltd T A 3 f D O . t 3 B J. Pharm. Pharmac., 1969, 21, 481-487 Received February 19, 1969 Simulation of the apparent effects of mebanazine on growth hormone by pair-feeding of control animals A. M. BARRETT Department o f Pharmacology, ICI Ltd., Pharmaceuticals Division, Alderley Park, Macclesfield, England The degree and duration of insulin hypoglycaemia was potentiated by chronic oral medication with mebanazine in rats. Hypo- physectomy alone increased sensitivity to insulin but did not abolish the potentiating effect of mebanazine. Chronic mebanazine treat­ ment (15 mg/kg/day) for 6 weeks markedly reduced weight gain, food and water consumption and pituitary growth hormone content, but the results were not significantly different from those in un­ medicated pair-fed controls. Similarly, immature rats treated with mebanazine had a significant reduction in the width of the tibial epiphysial cartilage but this was not different from that in pair-fed animals. After 18 h of fasting, acute administration of mebanazine had little effect on food consumption in the 2 h period following dosing but a significant effect over 24 h. In fed rats mebanazine in a single oral dose significantly reduced eating in the following 6 h. Treatment with mebanazine at 2-5 mg/kg for 15 days significantly reduced food intake but did not potentiate insulin hypoglycaemia. From the results it would appear that previous suggestions that mebanazine specifically interferes with growth hormone release are incorrect and the findings emphasize the importance of measuring food intake in experiments of long duration. Long-term administration of the monoamine oxidase inhibitor mebanazine to rats has been shown to potentiate the hypoglycaemic effects of both insulin and tolbut­ amide (Barrett, 1965). The results were compatible with the hypothesis that meban­ azine treatment interfered with the adrenergically mediated mechanisms for combating low circulating glucose levels. It was proposed that the pattern of insulin potentiation and hypotensive episodes during the clinical use of mebanazine (Wickstrom & Pettersson, 1964; Cooper & Keddie, 1964) might have a common origin.
Recommended publications
  • NINDS Custom Collection II
    ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC
    [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]
  • Pharmacological and Ionic Characterizations of the Muscarinic Receptors Modulating [3H]Acetylcholine Release from Rat Cortical Synaptosomes’
    0270.6474/85/0505-1202$02.00/O The Journal of Neuroscience CopyrIght 0 Society for Neuroscrence Vol. 5, No. 5, pp. 1202-1207 Printed in U.S.A. May 1985 Pharmacological and Ionic Characterizations of the Muscarinic Receptors Modulating [3H]Acetylcholine Release from Rat Cortical Synaptosomes’ EDWIN M. MEYER* AND DEBORAH H. OTERO Department of Pharmacology and Therapeutics, University of Florida School of Medicine, Gainesville, Florida 32610 Abstract brain (Gonzales and Crews, 1984). M,-receptors, however, appear pre- and postsynaptically in brain, are regulated by an intrinsic The muscarinic receptors that modulate acetylcholine membrane protein that binds to GTP (g-protein), and may not be release from rat cortical synaptosomes were characterized coupled to changes in phosphatidylinositol turnover. with respect to sensitivity to drugs that act selectively at M, The present studies were designed to determine whether M,- or or Ma receptor subtypes, as well as to changes in ionic Mp-receptors mediate the presynaptic modulation of ACh release. strength and membrane potential. The modulatory receptors These studies involve dose-response curves for the release of appear to be of the M2 type, since they are activated by synaptosomal [3H]ACh in the presence of selected muscarinic ago- carbachol, acetylcholine, methacholine, oxotremorine, and nists and antagonists, as well as treatments that selectively alter MI- bethanechol, but not by pilocarpine, and are blocked by or M,-receptor activity. Our results indicate that the presynaptic atropine, scopolamine, and gallamine (at high concentra- modulation of [3H]ACh release is mediated by MP- but not MI- tions), but not by pirenzepine or dicyclomine.
    [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]
  • Rat Animal Models for Screening Medications to Treat Alcohol Use Disorders
    ACCEPTED MANUSCRIPT Selectively Bred Rats Page 1 of 75 Rat Animal Models for Screening Medications to Treat Alcohol Use Disorders Richard L. Bell*1, Sheketha R. Hauser1, Tiebing Liang2, Youssef Sari3, Antoinette Maldonado-Devincci4, and Zachary A. Rodd1 1Indiana University School of Medicine, Department of Psychiatry, Indianapolis, IN 46202, USA 2Indiana University School of Medicine, Department of Gastroenterology, Indianapolis, IN 46202, USA 3University of Toledo, Department of Pharmacology, Toledo, OH 43614, USA 4North Carolina A&T University, Department of Psychology, Greensboro, NC 27411, USA *Send correspondence to: Richard L. Bell, Ph.D.; Associate Professor; Department of Psychiatry; Indiana University School of Medicine; Neuroscience Research Building, NB300C; 320 West 15th Street; Indianapolis, IN 46202; e-mail: [email protected] MANUSCRIPT Key Words: alcohol use disorder; alcoholism; genetically predisposed; selectively bred; pharmacotherapy; family history positive; AA; HAD; P; msP; sP; UChB; WHP Chemical compounds studied in this article Ethanol (PubChem CID: 702); Acamprosate (PubChem CID: 71158); Baclofen (PubChem CID: 2284); Ceftriaxone (PubChem CID: 5479530); Fluoxetine (PubChem CID: 3386); Naltrexone (PubChem CID: 5360515); Prazosin (PubChem CID: 4893); Rolipram (PubChem CID: 5092); Topiramate (PubChem CID: 5284627); Varenicline (PubChem CID: 5310966) ACCEPTED _________________________________________________________________________________ This is the author's manuscript of the article published in final edited form as: Bell, R. L., Hauser, S. R., Liang, T., Sari, Y., Maldonado-Devincci, A., & Rodd, Z. A. (2017). Rat animal models for screening medications to treat alcohol use disorders. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2017.02.004 ACCEPTED MANUSCRIPT Selectively Bred Rats Page 2 of 75 The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence.
    [Show full text]
  • Pharmacology Review(S)
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 200603 PHARMACOLOGY REVIEW(S) Tertiary Pharmacology/Toxicology Review From: Paul C. Brown, Ph.D., ODE Associate Director for Pharmacology and Toxicology, OND IO NDA: 200603 Agency receipt date: 12/30/2009 Drug: Lurasidone hydrochloride Applicant: Sunovion Pharmaceuticals (Originally submitted by Dainippon Sumimoto Pharma America, Inc.) Indication: schizophrenia Reviewing Division: Division of Psychiatry Products Background: The pharm/tox reviewer and team leader concluded that the nonclinical data support approval of lurasidone for the indication listed above. Reproductive and Developmental Toxicity: Reproductive and developmental toxicity studies in rats and rabbits revealed no evidence of teratogenicity or embryofetal toxicity. The high doses in the rat and rabbit embryofetal toxicity studies were 3 and 12 times, respectively, the maximum recommended human dose (80 mg) based on a body surface area comparison. Carcinogenicity: Lurasidone was tested in 2 year rat and mouse carcinogenicity studies. These studies were reviewed by the division and the executive carcinogenicity assessment committee. The committee concluded that the studies were adequate and that there was a drug-related increase in mammary carcinomas in female rats at doses of 12 mg/kg and higher and a drug-related increase in mammary carcinomas and adenoacanthomas and pituitary pars distalis adenomas in female mice. The applicant also provided data from various studies showing that lurasidone significantly increases prolactin in several different species including rats and mice. Conclusions: I agree with the division pharm/tox conclusion that this application can be approved from a pharm/tox perspective. The division recommends that lurasidone be labeled with pregnancy category B.
    [Show full text]
  • Tommunom U Vidutulinununun
    TOMMUNOMUS009765028B2 U VIDUTULINUNUNUN (12 ) United States Patent ( 10 ) Patent No. : US 9 ,765 , 028 B2 Woollam (45 ) Date of Patent: * Sep . 19 , 2017 ( 54 ) CRYSTALLINE FREEBASE FORMS OF A ( 56 ) References Cited BIPHENYL COMPOUND U . S . PATENT DOCUMENTS (71 ) Applicant: THERAVANCE BIOPHARMA R & D 3 , 903 , 137 A 9 / 1975 Miura et al. IP , LLC , South San Francisco , CA 6 , 693, 202 B1 2 /2004 Aggen et al . (US ) 7 , 524 , 880 B2 4 / 2009 Li et al . 7 , 700 , 777 B2 4 / 2010 Axt et al. ( 72 ) Inventor: Grahame Woollam , Basel (CH ) 8 , 242 , 137 B2 8 / 2012 Axt et al. 8 ,377 , 965 B2 2 / 2013 Axt et al. 8 , 541 , 451 B2 9 / 2013 Woollam ( 73 ) Assignee : Theravance Biopharma R & D IP , 8 , 716, 313 B2 5 / 2014 Axt et al. LLC , South San Francisco , CA (US ) 8 , 754 ,225 B2 6 / 2014 Colson 8 , 921 , 396 B2 12 /2014 Woollam ( * ) Notice : Subject to any disclaimer , the term of this 9 , 226, 896 B2 1 / 2016 Woollam patent is extended or adjusted under 35 2003/ 0018019 Al 1 / 2003 Meade et al. 2005 /0113413 A1 5 / 2005 Wilson et al . U . S . C . 154 ( b ) by 0 days . 2005 /0203133 A1 9 /2005 Mammen et al. This patent is subject to a terminal dis 2006 /0205949 A1 9 /2006 Dalziel et al . 2007 /0112027 Al 5 / 2007 Axt et al. claimer . 2010 /0048622 Al 2 /2010 Axt et al. (21 ) Appl. No .: 15 /206 ,877 FOREIGN PATENT DOCUMENTS (22 ) Filed : Jul. 11 , 2016 EP 0747355 Al 12 / 1996 (65 ) Prior Publication Data WO 2006 /099165 AL 9 / 2006 US 2017 / 0081283 A1 Mar .
    [Show full text]
  • Stria Terminalis Lesions Attenuate the Effects of Posttraining Oxotremorine and Atropine on Retention
    Psychobiology 1989, Vol. 17, 397-401 Stria terminalis lesions attenuate the effects of posttraining oxotremorine and atropine on retention INES B. INTROINI-COLLISON, YUTAKA ARAI, and JAMES L. McGAUGH Uniuersity of California, [ruine, California In these experiments, we examined the effects of posttraining administration of the choliner­ gic agonist oxotremorine and the cholinergic antagonist atropine on retention in rats with le­ sions of the stria terminalis (ST). Male Sprague-Dawley rats, with either sham or bilateral ST lesions, were trained in a one-trial step-through inhibitory-avoidance task and a Y-maze discrimi­ nation task. Immediately after training on each task, they received i.p. injections of saline, ox­ otremorine (50.0 "g/kg), or atropine (3.0 mg/kg). Retention of each task was tested 1 week follow­ ing training. Lesions of the ST did not affect retention of either task in otherwise untreated animals, but blocked both the memory-enhancing efIect of oxotremorine and the memory-impairing effect of atropine. These findings suggest that activation of pathways within the ST is involved in cholinergic influences on memory, and are consistent with the view that the amygdaloid com­ plex is involved in integrating neuromodulatory influences on memory storage. The findings of numerous studies have implicated cen­ tagonizes the amnestie effects of both morphine and ß• tral muscarinic-cholinergic mechanisms in memory endorphin (Baratti et al., 1984; Introini & Baratti, 1984). storage (Bartus, Dean, Goss, & Lippa, 1980; Bartus, These findings are in agreement with extensive neuro­ Dean, Pontecorvo, & Flicker, 1985; Davies, 1985; Karcz­ chemical evidence indicating that opioid agonists inhibit mar & Dun, 1978; Russell, 1982; Stratton & Petrinovich, acetylcholine release and that the inhibition is reversed 1963).
    [Show full text]
  • Tardive Dyskinesia
    Task Force Reports This is the eighteenth in a series of reports approved by the Board of Trustees of the American Psychiatric Association to give wider dissemination to the findings of APA's many commissions, committees, and task forces that are called upon to evaluate the state of the art in a problem area of current concern to the profession, to related disciplines, and to the public. The findings, opinions, and conclusions of the report do not necessarily represent the views of the officers, trustees, or all members of the Association. Each report, however, does represent the thoughtful judgment and findings of the task force of experts who composed it. These reports are considered a substantive contribution to the ongoing analysis and evaluation of problems, programs, issues, and practices in a given area of concern. Alan A. Stone, M.D. President, APA, 1979-80 Library of Congress Catalogue No. 80-65372 Copyright 1980 by the American Psychiatric Association 1400 K Street, N.W., Washington, D.C. 20005 Printed in U.S.A. 2nd Printing October, 1983 TARDIVE DYSKINESIA Report of the American Psychiatric Association Task Force on Late Neurological Effects of Antipsychotic Drugs Ross J. Baldessarini, M.D., Chairperson Jonathan O. Cole, M.D. John M. Davis, M.D. George Gardos, M.D., Consultant Sheldon H. Preskorn, M.D., Falk Fellow George M. Simpson, M.D. Daniel Tarsy, M.D., Invited Neurologist Approved for Publication by the Council on Research and Development John M. Davis, M.D., Chairperson Charles Gaitz, M.D. Edward Joel Sachar, M.D. George Winokur, M.D.
    [Show full text]
  • Characterization of a Novel M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator Radioligand, [3H]PT-1284
    1521-0111/90/3/177–187$25.00 http://dx.doi.org/10.1124/mol.116.104737 MOLECULAR PHARMACOLOGY Mol Pharmacol 90:177–187, September 2016 Copyright ª 2016 by The American Society for Pharmacology and Experimental Therapeutics Characterization of a Novel M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator Radioligand, [3H]PT-1284 Deborah L. Smith, Jennifer E. Davoren, Jeremy R. Edgerton, John T. Lazzaro, Che-Wah Lee, Sarah Neal, Lei Zhang, and Sarah Grimwood Neuroscience and Pain Research Unit (D.L.S., J.R.E., S.N., S.G.) and Worldwide Medicinal Chemistry (J.E.D., L.Z.), Pfizer Inc., Cambridge, Massachusetts; Primary Pharmacology Group (J.T.L.) and Worldwide Medicinal Chemistry (C.-W.L.), Pfizer Inc., Groton, Connecticut Received April 14, 2016; accepted June 30, 2016 Downloaded from ABSTRACT 3 3 Selective activation of the M1 muscarinic acetylcholine recep- of ACh required to inhibit [ H]N-methylscopolamine ([ H]NMS) tor (mAChR) via a positive allosteric modulator (PAM) is a new binding to M1, left-shifting the ACh Ki approximately 19-fold at approach for the treatment of the cognitive impairments asso- 10 mM. Saturation analysis of a human M1 mAChR stable cell line 3 molpharm.aspetjournals.org ciated with schizophrenia and Alzheimer’s disease. Herein, showed that [ H]PT-1284 bound to M1 mAChR in the presence of we describe the characterization of an M1 PAM radioligand, 1mMAChwithKd, 4.23 nM, and saturable binding capacity (Bmax), 8-((1S,2S)-2-hydroxycyclohexyl)-5-((6-(methyl-t3)pyridin-3-yl)- 6.38 pmol/mg protein. M1 selective PAMs were shown to inhibit methyl)-8,9-dihydro-7H-pyrrolo[3,4-hour]quinolin-7-one [3H]PT-1284 binding in a concentration-responsive manner, whereas 3 ([ H]PT-1284), as a tool for characterizing the M1 allosteric M1 allosteric and orthosteric agonists showed weak affinity (.30 mM).
    [Show full text]
  • Title Page the Constitutive Activity of the Human Muscarinic M3 Receptor
    JPET Fast Forward. Published on December 24, 2009 as DOI: 10.1124/jpet.109.163188 JPET FastThis Forward. article has not Published been copyedited on andDecember formatted. The 24, final 2009 version as mayDOI:10.1124/jpet.109.163188 differ from this version. JPET#163188 Title Page The constitutive activity of the human muscarinic M3 receptor Downloaded from unmasks differences in the pharmacology of anticholinergics. Paola Casarosa, Tobias Kiechle, Peter Sieger, Michael Pieper and Florian Gantner. jpet.aspetjournals.org Dept. of Pulmonary Diseases Research (P.C., T.K., M.P. and F.G.) and Drug Discovery Support (P.S.), Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, at ASPET Journals on September 27, 2021 Germany 1 Copyright 2009 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on December 24, 2009 as DOI: 10.1124/jpet.109.163188 This article has not been copyedited and formatted. The final version may differ from this version. JPET#163188 Running Title Page Running Title: Evidence for Differential Inverse Agonism at the hM3 Receptor Corresponding author: Paola Casarosa, Ph.D. Contact Information: Dept. of Pulmonary Diseases Research, BI Pharma GmbH & Co. KG, Birkendorferstrasse 65, Biberach an der Riss, Germany E-mail: [email protected] Phone: +49-7351-5493196 Downloaded from Fax: +49-7351-8393196 Number of text pages: 33 jpet.aspetjournals.org Number of tables: 2 Number of figures: 6 Number of references: 29 at ASPET Journals on September 27, 2021 Number of words in the abstract: 250 Number of words in the introduction: 466 Number of words in the discussion: 1496 Non-standard abbreviations: human muscarinic receptor, hM-R; acetylcholine, ACh; long acting muscarinic antagonist, LAMA; chronic obstructive pulmonary disease, COPD; Chinese hamster ovary, CHO.
    [Show full text]
  • Cholinergic Modulation During Acquisition of Olfactory Fear Conditioning Alters Learning and Stimulus Generalization in Mice
    Downloaded from learnmem.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Brief Communication Cholinergic modulation during acquisition of olfactory fear conditioning alters learning and stimulus generalization in mice Eloisa Pavesi, Allison Gooch, Elizabeth Lee, and Max L. Fletcher1 Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamyl- amine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly reduced freezing. To test whether cholinergic manipulation affected fear generalization, mice were presented with odors similar to the trained odor. Generalization was increased following pretraining scopolamine, while the muscarinic agonist oxotremorine de- creased generalization. These results suggest that muscarinic neurotransmission during the acquisition of olfactory associ- ation modulates both the strength and specificity of learning. The olfactory system receives cholinergic input from the horizon- suggesting that muscarinic activation is important for the acquisi- tal limb of the diagonal band of Broca (HDB) (Zaborszky et al. tion of olfactory fear learning. We next tested whether manipula- 1986). Blocking olfactory system cholinergic receptors disrupts tion of mAChRs could also affect the specificity of the fear several aspects of olfactory processing including olfactory short- learning. In this case, mice trained to a single odor tend to freeze term memory (Hunter and Murray 1989; Paolini and McKenzie at similar levels when tested with other structurally similar odors, 1993; Miranda et al.
    [Show full text]