Ionotropic Glutamate Receptors
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NMDA Receptor Dynamics Dictate Neuronal Plasticity and Function
NMDA Receptor Dynamics Dictate Neuronal Plasticity and Function Tommy Weiss Sadan, Ph.D. and Melanie R. Grably, Ph.D. N-Methyl-D-Aspartate Receptor (NMDAR) are ubiquitously expressed along the central nervous system and are instrumental to various physiological processes such as synaptic plasticity and learning. Nevertheless, several mental disabilities including schizophrenia and Alzheimer’s disease are all related to NMDAR dysfunction. Here, we review many aspects of NMDAR function and regulation and describe their involvement in pathophysiological states using Alomone Labs products. Right: Cell surface detection of GluN2B in rat hippocampal neurons. Introduction Mechanism of Action Glutamate is a key neuro-transmitter in the central nervous system and NMDAR activation depends on sequential conformational changes to acts on a variety of cell surface receptors, collectively termed ionotropic relieve the magnesium blockade which is achieved by rapid membrane glutamate receptors (iGluRs)15. The N-Methyl-D-Aspartate receptors (NMDAR) depolarization and binding of both glycine and glutamate ligands6, 21. This in are members of the iGluR superfamily and are pivotal to many physiological turn removes the inhibitory electrostatic forces of magnesium and enables processes such as the formation of long term memory, synaptic plasticity calcium influx and transmission of long lasting signals (i.e. long-term and many other cognitive functions. Therefore, it is not surprising that potentiation), a key mechanism to learning and memory formation10. -
Effects of Chronic Systemic Low-Impact Ampakine Treatment On
Biomedicine & Pharmacotherapy 105 (2018) 540–544 Contents lists available at ScienceDirect Biomedicine & Pharmacotherapy journal homepage: www.elsevier.com/locate/biopha Effects of chronic systemic low-impact ampakine treatment on neurotrophin T expression in rat brain ⁎ Daniel P. Radin , Steven Johnson, Richard Purcell, Arnold S. Lippa RespireRx Pharmaceuticals, Inc., 126 Valley Road, Glen Rock, NJ, 07452, United States ARTICLE INFO ABSTRACT Keywords: Neurotrophin dysregulation has been implicated in a large number of neurodegenerative and neuropsychiatric Ampakine diseases. Unfortunately, neurotrophins cannot cross the blood brain barrier thus, novel means of up regulating BDNF their expression are greatly needed. It has been demonstrated previously that neurotrophins are up regulated in Cognitive enhancement response to increases in brain activity. Therefore, molecules that act as cognitive enhancers may provide a LTP clinical means of up regulating neurotrophin expression. Ampakines are a class of molecules that act as positive Neurotrophin allosteric modulators of AMPA-type glutamate receptors. Currently, they are being developed to prevent opioid- NGF induced respiratory depression without sacrificing the analgesic properties of the opioids. In addition, these molecules increase neuronal activity and have been shown to restore age-related deficits in LTP in aged rats. In the current study, we examined whether two different ampakines could increase levels of BDNF and NGF at doses that are active in behavioral measures of cognition. Results demonstrate that ampakines CX516 and CX691 induce differential increases in neurotrophins across several brain regions. Notable increases in NGF were ob- served in the dentate gyrus and piriform cortex while notable BDNF increases were observed in basolateral and lateral nuclei of the amygdala. -
Characterization of a Domoic Acid Binding Site from Pacific Razor Clam
Aquatic Toxicology 69 (2004) 125–132 Characterization of a domoic acid binding site from Pacific razor clam Vera L. Trainer∗, Brian D. Bill NOAA Fisheries, Northwest Fisheries Science Center, Marine Biotoxin Program, 2725 Montlake Blvd. E., Seattle, WA 98112, USA Received 5 November 2003; received in revised form 27 April 2004; accepted 27 April 2004 Abstract The Pacific razor clam, Siliqua patula, is known to retain domoic acid, a water-soluble glutamate receptor agonist produced by diatoms of the genus Pseudo-nitzschia. The mechanism by which razor clams tolerate high levels of the toxin, domoic acid, in their tissues while still retaining normal nerve function is unknown. In our study, a domoic acid binding site was solubilized from razor clam siphon using a combination of Triton X-100 and digitonin. In a Scatchard analysis using [3H]kainic acid, the partially-purified membrane showed two distinct receptor sites, a high affinity, low capacity site with a KD (mean ± S.E.) of 28 ± 9.4 nM and a maximal binding capacity of 12 ± 3.8 pmol/mg protein and a low affinity, high capacity site with a mM affinity for radiolabeled kainic acid, the latter site which was lost upon solubilization. Competition experiments showed that the rank order potency for competitive ligands in displacing [3H]kainate binding from the membrane-bound receptors was quisqualate > ibotenate > iodowillardiine = AMPA = fluorowillardiine > domoate > kainate > l-glutamate. At high micromolar concentrations, NBQX, NMDA and ATPA showed little or no ability to displace [3H]kainate. In contrast, Scatchard analysis 3 using [ H]glutamate showed linearity, indicating the presence of a single binding site with a KD and Bmax of 500 ± 50 nM and 14 ± 0.8 pmol/mg protein, respectively. -
Advances in the Synthesis of 5- and 6-Substituted Uracil Derivatives
701xml UOPP_A_438055 October 9, 2009 12:27 UOPP #438055, VOL 41, ISS 6 Advances in the Synthesis of 5- and 6-Substituted Uracil Derivatives Javier I. Bardag´ı and Roberto A. Rossi QUERY SHEET This page lists questions we have about your paper. The numbers displayed at left can be found in the text of the paper for reference. In addition, please review your paper as a whole for correctness. There are no Editor Queries for this paper. TABLE OF CONTENTS LISTING The table of contents for the journal will list your paper exactly as it appears below: Advances in the Synthesis of 5- and 6-Substituted Uracil Derivatives Javier I. Bardag´ı and Roberto A. Rossi 701xml UOPP_A_438055 October 9, 2009 12:27 Organic Preparations and Procedures International, 41:1–36, 2009 Copyright © Taylor & Francis Group, LLC ISSN: 0030-4948 print DOI: 10.1080/00304940903378776 Advances in the Synthesis of 5- and 6-Substituted Uracil Derivatives Javier I. Bardag´ı and Roberto A. Rossi INFIQC, Departamento de Qu´ımica Organica,´ Facultad de Ciencias Qu´ımicas, Universidad Nacional de Cordoba,´ Ciudad Universitaria, 5000 Cordoba,´ ARGENTINA INTRODUCTION ................................................................................... 2 I. Uracils with Carbon-based Substituent ................................................. 3 1. C(Uracil)-C(sp3) Bonds............................................................................ 3 a. Perfluoroalkyl Compounds...................................................................12 2. C(Uracil)-C(sp2) Bonds...........................................................................13 -
(12) Patent Application Publication (10) Pub. No.: US 2004/0224012 A1 Suvanprakorn Et Al
US 2004O224012A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0224012 A1 Suvanprakorn et al. (43) Pub. Date: Nov. 11, 2004 (54) TOPICAL APPLICATION AND METHODS Related U.S. Application Data FOR ADMINISTRATION OF ACTIVE AGENTS USING LIPOSOME MACRO-BEADS (63) Continuation-in-part of application No. 10/264,205, filed on Oct. 3, 2002. (76) Inventors: Pichit Suvanprakorn, Bangkok (TH); (60) Provisional application No. 60/327,643, filed on Oct. Tanusin Ploysangam, Bangkok (TH); 5, 2001. Lerson Tanasugarn, Bangkok (TH); Suwalee Chandrkrachang, Bangkok Publication Classification (TH); Nardo Zaias, Miami Beach, FL (US) (51) Int. CI.7. A61K 9/127; A61K 9/14 (52) U.S. Cl. ............................................ 424/450; 424/489 Correspondence Address: (57) ABSTRACT Eric G. Masamori 6520 Ridgewood Drive A topical application and methods for administration of Castro Valley, CA 94.552 (US) active agents encapsulated within non-permeable macro beads to enable a wider range of delivery vehicles, to provide longer product shelf-life, to allow multiple active (21) Appl. No.: 10/864,149 agents within the composition, to allow the controlled use of the active agents, to provide protected and designable release features and to provide visual inspection for damage (22) Filed: Jun. 9, 2004 and inconsistency. US 2004/0224012 A1 Nov. 11, 2004 TOPCAL APPLICATION AND METHODS FOR 0006 Various limitations on the shelf-life and use of ADMINISTRATION OF ACTIVE AGENTS USING liposome compounds exist due to the relatively fragile LPOSOME MACRO-BEADS nature of liposomes. Major problems encountered during liposome drug Storage in vesicular Suspension are the chemi CROSS REFERENCE TO OTHER cal alterations of the lipoSome compounds, Such as phos APPLICATIONS pholipids, cholesterols, ceramides, leading to potentially toxic degradation of the products, leakage of the drug from 0001) This application claims the benefit of U.S. -
University Microfilms
INFORMATION TO USERS This dissertation was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1. The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You w ill find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the first row and continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. -
Regulation of Extracellular Arginine Levels in the Hippocampus in Vivo
Regulation of Extracellular Arginine Levels in the Hippocampus In Vivo by Joanne Watts B.Sc. (Hons) r Thesis submitted for the degree of Doctor of Philosophy in the Faculty of Science, University of London The School of Pharmacy University of London ProQuest Number: 10105113 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10105113 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Nitric oxide (NO) has emerged as an ubiquitous signaling molecule in the central nervous system (CNS). NO is synthesised from molecular oxygen and the amino acid L-arginine (L- ARG) by the enzyme NO synthase (NOS), and the availability of L-ARG has been implicated as the limiting factor for NOS activity. Previous studies have indicated that L- ARG is localised in astrocytes in vitro and that the in vitro activation of non-N-methyl-D- aspartate (NMDA) receptors, as well as the presence of peroxynitrite (ONOO ), led to the release of L-ARG. Microdialysis was therefore used in this study to investigate whether this held true in vivo. -
(12) United States Patent (10) Patent No.: US 8,748,131 B2 Ford (45) Date of Patent: Jun
USOO8748131B2 (12) United States Patent (10) Patent No.: US 8,748,131 B2 Ford (45) Date of Patent: Jun. 10, 2014 (54) CHIMERIC NEUREGULINS AND METHOD in Neuregulin-1/ErbB Signaling. The Journal of Biological Chemis OF MAKING AND USE THEREOF try vol. 285, No. 41, pp. 31388-31398, Oct. 8, 2010.* Veronese et al., PEGylation. Successful approach to drug delivery. (71) Applicant: Morehouse School of Medicine, Drug Discovery Today vol. 10, No. 21 Nov. 2005, 1451-1458.* Atlanta, GA (US) Carraway et al., Neuregulin-2, a new ligand ErbB3/ErbB4-receptor tyrosine kinases. Nature, vol. 387, May 29, 1997, 512-516.* (72) Inventor: Byron D. Ford, Atlanta, GA (US) Higashiyamaet al., ANovel Brain-Derived Member of the Epidermal Growth Factor Family That Interacts with ErbB3 and ErbB4. J. (73) Assignee: Morehouse School of Medicine, Biochem. 122,675-680 (1997).* Atlanta, GA (US) Fischbach et al., “ARIA: A Neuromuscular Junction Neuregulin.” Annual Review of Neuroscience, 1997, pp. 429–458, vol. 20. (*) Notice: Subject to any disclaimer, the term of this Buonanno et al., “Neuregulin and ErbB receptor signaling pathways patent is extended or adjusted under 35 in the nervous system.” Current Opinion in Neurobiology, 2001, pp. U.S.C. 154(b) by 0 days. 287-296, vol. 11. Burden et al., “Neuregulins and Their Receptors: A Versatile Signal Appl. No.: 13/627,555 ing Module in Organogenesis and Oncogenesis. Neuron, 1997, pp. (21) 847-855, vol. 18. Fu et al., “Cdk5 is involved in neuregulin-induced AChR expression (22) Filed: Sep. 26, 2012 at the neuromuscular junction.” Nature Neuroscience, Apr. -
University of Florida Thesis Or Dissertation Formatting
THE PROTECTIVE EFFECTS OF PLASMA GELSOLIN AND ALPHA 1-ANTITRYPSIN ON ISCHEMIC STROKE OUTCOME IN RATS By HUONG LE MOLDTHAN A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2012 1 © 2012 Huong Le Moldthan 2 To my beloved grandmother, parents and husband, Matthew Michael Moldthan 3 ACKNOWLEDGMENTS Obtaining my doctorate has been the most challenging goal of my life so far. Yet, starting is the best decision that I will never regret. During the journey to this dissertation, both figurative as well as literal, I am deeply indebted to the many people who have provided me inspiration and supported my studies. My greatest gratitude goes to Dr. Jeffrey Hughes, my former mentor who gave me an opportunity to do research in his lab and for his excellent supervision, as well as his great sense of humor. I would like to gratefully thank Dr. Sihong Song for continuing to guide me in a new project when Dr. Hughes left. I also would like to express my thanks to Dr. Michael King and other committee members, Dr. Christopher Batich and Dr. Guenther Hochhaus for their detailed comments and great suggestions. Without their guidance, I would not have had such a great experience in completing this challenging project. I would like to express my special thanks to Dr. Aaron Hirko, for his constant help, patience and invaluable advice. A sincere thank you goes to Jeffrey Thinschmidt, who was always willing to help me with handling animals, performing laser-Doppler imaging experiments, providing great comments on dissertation as well as my talks, and contributing to a very happy lab environment. -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
Stems for Nonproprietary Drug Names
USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol -
Neuroenhancement in Healthy Adults, Part I: Pharmaceutical
l Rese ca arc ni h li & C f B o i o l e Journal of a t h n Fond et al., J Clinic Res Bioeth 2015, 6:2 r i c u s o J DOI: 10.4172/2155-9627.1000213 ISSN: 2155-9627 Clinical Research & Bioethics Review Article Open Access Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review Fond G1,2*, Micoulaud-Franchi JA3, Macgregor A2, Richieri R3,4, Miot S5,6, Lopez R2, Abbar M7, Lancon C3 and Repantis D8 1Université Paris Est-Créteil, Psychiatry and Addiction Pole University Hospitals Henri Mondor, Inserm U955, Eq 15 Psychiatric Genetics, DHU Pe-psy, FondaMental Foundation, Scientific Cooperation Foundation Mental Health, National Network of Schizophrenia Expert Centers, F-94000, France 2Inserm 1061, University Psychiatry Service, University of Montpellier 1, CHU Montpellier F-34000, France 3POLE Academic Psychiatry, CHU Sainte-Marguerite, F-13274 Marseille, Cedex 09, France 4 Public Health Laboratory, Faculty of Medicine, EA 3279, F-13385 Marseille, Cedex 05, France 5Inserm U1061, Idiopathic Hypersomnia Narcolepsy National Reference Centre, Unit of sleep disorders, University of Montpellier 1, CHU Montpellier F-34000, Paris, France 6Inserm U952, CNRS UMR 7224, Pierre and Marie Curie University, F-75000, Paris, France 7CHU Carémeau, University of Nîmes, Nîmes, F-31000, France 8Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany *Corresponding author: Dr. Guillaume Fond, Pole de Psychiatrie, Hôpital A. Chenevier, 40 rue de Mesly, Créteil F-94010, France, Tel: (33)178682372; Fax: (33)178682381; E-mail: [email protected] Received date: January 06, 2015, Accepted date: February 23, 2015, Published date: February 28, 2015 Copyright: © 2015 Fond G, et al.