Back Matter (PDF)

Total Page:16

File Type:pdf, Size:1020Kb

Back Matter (PDF) The Editor of The Journal of Pharmacology and Experimental Therapeutics wishes to express appreciation to the following colleagues who acted at Guest Editors for Specific Fields in 1994. Martin W. Adler Allan M. Lefer Edson X. Albuquerque Roberto Levi Vernon S. Bishop Benedict R. Lucchesi Theodore J. Cicero Irwin LucId Marlene L. Cohen David R. Manning Alan Frazer William H. Morse Robert Freedman Garth Powis Eitan Friedman Roger D. Spealman Ray W. Fuller Milt Teitler Richard Gillis Mary Vore Elizabeth H. Jeffery Michael Williams Additionally, sincere thanks are due to 1039 of our colleagues not on the Editorial Advisory Board who reviewed articles for the Journal in 1994. Their contributions are acknowledged individually in the Annual Report of The Journal to The Board of Publications Trustees of The American Society for Pharmacology and Experimental Therapeutics. INDEX Volume 273, April-June, 1995 A-85653, repeated daily, effects on rota- tor binding and in vivo activities beta-i, effects in SNS-evoked adrenal tion and striatal c-fos expression, for anandamide analogs, 1172 catecholamine release, in anes- 1483 Adams, J. L., see Chabot-Fletcher, M. C., thetized dogs, 1337 Abecarnil, modulation of basal and stress- 1147 Advenier, C., see F#{233}l#{233}tou,M., 1071 induced release of acetyicholine Adams, J. U., see Liu-Chen, L.-Y., 1047 Afferent nerves, capsaicin-sensitive, regu- and dopamine in rat brain by, 241 Adams, M., see Cicero, T. J., 386 lation of jejunal arterioles by, in Absence seizures, GHB-induced, endoge- Adenosine, metabolism of exogenous cyclic N. brasiliensis-sensitized rats, nous GABA in, in rat, 1534 AMP to, in rat kidney, 728 337 [3HIABT-418, receptor binding character- Adenosine analogues, TNF-a inhibition v-Agatoxin-IVA, blockade of voltage- istics, in rat brain, 1434 by, 1506 sensitive calcium channels by, at Abuse, see Alcohol abuse; Drug abuse Adenosine receptors mouse neuromuscular junction, Acetaminophen, cytotoxicity in human A1 248 CYP2E1-transfected HepG2 cells, interaction with caffeine, effects on Ahmed, M. S., see Cemerikic, B., 987 1497 hippocampal acetyicholine re- Ahmmed, G. U., see Yoshida, A., 702 Acetylcholine lease, 637 Akai, T., Ozawa, M., Yamaguchi, M., basal and stress-induced release, modu- potassium current activated by, char- Mizuta, E. and Kuno, S.: Combi- lation by abecarnil and imidaze- acterization of, in rat locus cer- nation treatment of the partial nil, in rat brain, 241 uleus neurons, 537 D2 agonist terguride with the D1 hippocampal release, caffeine effects on, agonist modulation of intraocular pres- agonist SKF 82958 in 1-methyl- 4-phenyl-i,2,3,6-tetrahydropyri- 637 sure by, in rabbits, 320 interaction with K channel blockers, Adenylate cyclase dine-lesioned parkinsonian cyno- molgus monkeys, 309 effects on atrial repolarization, beta adrenergic response of, in rat brain, Akima, M., see Takanashi, H., 624 1095 415 Albumin, serum, role in nitric oxide dose- Na influx and catecholamine secretion bradykinin inhibition of, colon contrac- response, in isolated perfused rat evoked by, reduction by ginseng tion evoked by, 344 kidney, 855 saponins, in bovine adrenal chro- Adhesion molecules, role in cardiovascular Albuquerque, E. X., see Ishihara, K., 1459, maffin cells, 629 pharmacology, meeting review, 1471 signal transduction pathways in gall- 569 Albuterol, salmeterol blockade of inhibi- bladder muscle, 650 Adler, M. W., see Belkowski, S. M., 1491 tion of eosinophil secretion by, Acetylcholine receptors Adrenal chromaffin cells, ACh-evoked 850 muscarinic Na influx and catecholamine se- Alcohol abuse, promotion by low brain do- bladder subtypes, 959 cretion in, reduction by ginseng pamine, 373 gallbladder muscle subtypes, 650 saponins, in bovine, 629 Alfentanil, antinociceptive effects in tail- interaction with K channel blockers, Adrenal gland, catecholamine release in, withdrawal procedure, buprenor- effects on atrial repolarization, SNS-evoked, effects of beta adre- phine antagonism of, in rhesus noceptors in, in anesthetized 1095 monkey, 1345 regulation of cardiac CFTR Cl cur- dogs, 1337 Alicea, C., see Belkowski, S. M., 1491 Adrenergic nerves, ear artery, facilitatory rent by, effects of quaternary am- Alkondon, M., see Ishihara, K., 1459, 1471 prejunctional purinoceptors on, monium compounds on, 470 Allavena, A., see Martelli, A., 113 role in cicletanine effects on kidney in rabbit, 1390 Allergy function, 1197 Adrenergic neurons, modulation by SB 202235 asthmatic effects in, in mod- nicotinic 5-HT1A receptors, in rat, 1032 els, 1147 ABT-418 binding characteristics, in Adrenergic receptors trimellitic anhydride, role of comple- rat brain, 1434 alpha-2 ment system in, in lung, 793 hippocampal, lead effects on, in rat, medullary, effects in conscious spon- Ailing, K., see Pell#{243}n, R., 138 1471 taneously hypertensive rats, 1162 Alloantigen, specific CTL activity, effects Acid secretion, in gastric glands, effects of modulation of spinal sympathetic re- of exogenous corticosterone on, in PDE IV inhibitors on, in rabbit, flex by, in rat, 380 mice, 823 1396 13H]RX 821002 vs [3H]rauwolscine Allografts, heart, gramicidin prolongation Action potential, dimethyl sulfoxide ef- binding, in nine tissues and cell of survival, in rat, 223 fects on, in guinea pig ventricular lines, 1287 Aloyo, V. J., Ruffin, J. S., Pazdalski, P. 5., preparations, 1273 alpha-i, agonist preconditioning, in rat Kirifides, A. L. and Harvey, J. A.: Action potential duration, effects of inter- hearts, 689 [3H]WIN 35,428 binding in the action between K channel block- beta caudate nucleus of the rabbit: Ev- ers and acetylcholine on, 1095 brain signaling, in rat, 415 idence for a single site on the do- Activated protein C, antiinflammatory ef- effects in SNS-evoked adrenal cate- pamine transporter, 435 fects, in rat models, 193 cholamine release, in anesthe- Alper, S. L., see Brugnara, C., 266 Activity stress gastric lesions, dopamine tized dogs, 1337 Amantadine, renal transport, site-selec- Dl and D2 receptor effects in, in beta-2 tive effect of bicarbonate on, 72 rats, 1001 effects in SNS-evoked adrenal cate- Ambler, S. J., see Chrandasekhar, S., 1519 Adams, I. B. , Ryan, W., Singer, M., cholamine release, in anesthe- y-Aminobutyric acid Thomas, B. F., Compton, D. R., tized dogs, 1337 ethanol interaction, prediction by zolpi- Razdan, R. K. and Martin, B. R.: salmeterol blockade of eosinophil in- dem effects on GABA-induced in- Evaluation of cannabinoid recep- hibition by, 850 hibition, in rat brain regions, 526 1562 Index Vol. 273 in GHB-induced absence seizures, in Anorectic agents, effects on deprivation- sympathetic vasoconstriction of, modu- rat, 1534 induced feeding and taste aver- lation by sensory nerves and NO 5-HT interactions in substantia nigra, sion conditioning, in rats, 1203 in, in rat iris, 918 modulation of MDMA-induced Antiarrhythmics Ashkenazi, I. E., see Gozes, I., 161 striatal dopamine release by, class-I-type, sodium channel blockade Asin, K. E., Bednarz, L., Nikkel, A. and 1063 by, postischemia, 1403 Perner, R.: Rotation and striatal presynaptic GHB and GABAB receptor- electrophysiologic effects c-fos expression after repeated, mediated release of, in rat tha- effects of infarct healing on, 315 daily treatment with selective do- lamic ventrobasal nucleus, 1534 in guinea pig cardiac isolated prepa- pamine receptor agonists and -y-Aminobutyric acidB, presynaptic inhibi- rations, 1264 levodopa, 1483 tion by adenosine, in midbrain inhibition of G-protein and K channels Asthma, allergic, SB 202235 effects in, in dopamine neurons, 576 by, in thyroid cells, 702 models, 1147 2-Amino-N-(1,2-diphenylethyl)acetamide Antibiotics, (3-lactam, intestinal transport, Atenolol, effects in SNS-evoked adrenal hydrochloride, anticonvulsant ef- in rat, rabbit and human small catecholamine release, in anes- ficacy/safety properties of, 1023 intestines, 26 thetized dogs, 1337 p-Aminohippurate, renal transport, in Antigen, 6-THC modulation of macro- ATRA, see Retinoic acid rabbit renal basolateral mem- phage processing of, 1216 Atrial natriuretic peptide, endothelin ef- brane vesicles, 146 Antimalarials, amodiaquine metabolism fects dependent on, modulation by inhibitors Aminopyrine, secretion in gastric glands, and activity, effects of chemical of neutral endopep- effects of PDE N inhibitors on, in substitution on, in mouse, 393 tidase and cGMP-PDE, 744 rabbit, 1396 Antinociception Atrial repolarization, effects of interaction Ammonium, quaternary compounds, mus- anandamide, in mice, 1235 between K channel blockers and carinic regulation of cardiac 9-THC, anandamide blockade of, in acetylcholine on, 1095 Audinot, V., see Gobert, A., 1032; Milan, CFTR Cl current by, 470 mice, 1235 M. J., 1418; Schreiber, R., 101 Amodiaquine, metabolism and activity, ef- dynorphin A-(2-17) naloxone-insensi- Auta, J., see Thompson, D. M., 1307 fects of chemical substitution on, tive, in writhing assay, 802 Autoradiography, localization and charac- in mouse, 393 fluoroanandamide, in mice, 1235 terization of[3H]a-trinositol bind- Amphetamine, dose-related effects on zif/ intrathecal clonidine, mediation by spi- ing sites, in human and mamma- 268 and preprodynorphin mRNA nal nonadrenergic imidazoline re- ceptors, in rat, 1057 han tissues, 461 expression, in rat forebrain, 909 morphine, tolerance to, prevention with Autoreceptors Analgesia, see also Antinociception irreversible opioid antagonists, muscannic, m2 subtype identification, morphine, sensitivity to, adverse effects 680 in rat striatum, 273 of paternal opiates exposure
Recommended publications
  • Tetrandrine Attenuates Left Ventricular Dysfunction in Rats with Myocardial Infarction
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 21: 119, 2021 Tetrandrine attenuates left ventricular dysfunction in rats with myocardial infarction YOUYANG WU, WEI ZHAO, FANHAO YE, SHIWEI HUANG, HAO CHEN, RUI ZHOU and WENBING JIANG Department of Cardiology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China Received March 16, 2020; Accepted September 16, 2020 DOI: 10.3892/etm.2020.9551 Abstract. The present study aimed to determine whether the levels of LVIDd and LVIDs were significantly higher; tetrandrine could attenuate left ventricular dysfunction and however, the levels of EF% and FS% were lower compared remodeling in rats with myocardial infarction. Sprague‑Dawley with those in the sham operation group, which was alleviated rats were randomly divided into six groups (n=5/group) as by tetrandrine. H&E results showed that tetrandrine allevi‑ follows: i) Healthy control group; ii) sham operation group; ated the pathological characteristics of myocardial infarction iii) myocardial infarction model group; iv) myocardial infarc‑ model rats. Furthermore, tetrandrine significantly inhibited tion + low‑dose tetrandrine group (10 mg/kg); v) myocardial myocardial cell apoptosis in rats with myocardial infarction. infarction + medium‑dose tetrandrine group (50 mg/kg); Tetrandrine significantly inhibited the levels of TG, TC and and vi) myocardial infarction + high‑dose tetrandrine group LDL and increased the levels of HDL in the arterial blood of (80 mg/kg). Left ventricular end‑diastolic diameter (LVIDd), rats with myocardial infarction. These findings revealed that left ventricular end‑systolic diameter (LVIDs), ejection frac‑ tetrandrine could attenuate left ventricular dysfunction in rats tion (EF%) and left ventricular fractional shortening rate (FS%) with myocardial infarction, which might be associated with were measured using ultrasonography.
    [Show full text]
  • Specifications of Approved Drug Compound Library
    Annexure-I : Specifications of Approved drug compound library The compounds should be structurally diverse, medicinally active, and cell permeable Compounds should have rich documentation with structure, Target, Activity and IC50 should be known Compounds which are supplied should have been validated by NMR and HPLC to ensure high purity Each compound should be supplied as 10mM solution in DMSO and at least 100µl of each compound should be supplied. Compounds should be supplied in screw capped vial arranged as 96 well plate format.
    [Show full text]
  • 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]
  • Pharmaceutical Targeting the Envelope Protein of SARS-Cov-2: the Screening for Inhibitors in Approved Drugs
    Pharmaceutical Targeting the Envelope Protein of SARS-CoV-2: the Screening for Inhibitors in Approved Drugs Anatoly Chernyshev XR Pharmaceuticals Ltd., Cambridge, New Zealand email: [email protected] Abstract An essential overview of the biological role of coronavirus viroporin (envelope protein) is given, together with the effect of its known inhibitors on the life cycle of coronavirus. A docking study is conducted using a set of known drugs approved worldwide (ca. 6000 compounds) on a structure of the SARS-CoV-2 viroporin modelled from the published NMR-resolved structures. The screening has identified 36 promising drugs currently on the market, which could be proposed for pre-clinical trials. Introduction Viral ion channels (viroporins) are known since at least 1992, when the M2 channel of influenza A virus has been discovered. These ion channels exist in a form of homotetra- (e.g. the M2 channel) or homopentamers (e.g. coronavirus E channel); each subunit is 50–120 aminoacids long and has at least one transmembrane domain (TMD). The pore formed by the transmembrane domains of the oligomer acts as an ion channel. It is speculated that viroporins initiate a leakage in host cell membranes, which alters the tans-membrane potential and serves as a marker of viral infection [1]. SARS coronaviruses were found to have at least three types of ion channels: E and 8a (both with single TMD, forming pentameric assemblies), and 3a with three TMD [2, 3]. Both proteins E and 3a possess PDZ domain- binding motif (PBM). In the protein E it is the last four aminoacids in the C-terminus (DLLV, Table 1).
    [Show full text]
  • A Machine Learning Approach to Drug Repositioning Based on Drug Expression Profiles: Applications to Schizophrenia and Depression/Anxiety Disorders
    A machine learning approach to drug repositioning based on drug expression profiles: Applications to schizophrenia and depression/anxiety disorders Kai Zhao1 and Hon-Cheong So*1,2 1School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong 2KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Zoology Institute of Zoology and The Chinese University of Hong Kong Corresponding author: Hon-Cheong So. Email: [email protected] Abstract Development of new medications is a very lengthy and costly process. Finding novel indications for existing drugs, or drug repositioning, can serve as a useful strategy to shorten the development cycle. In this study, we present an approach to drug discovery or repositioning by predicting indication for a particular disease based on expression profiles of drugs, with a focus on applications in psychiatry. Drugs that are not originally indicated for the disease but with high predicted probabilities serve as good candidates for repurposing. This framework is widely applicable to any chemicals or drugs with expression profiles measured, even if the drug targets are unknown. It is also highly flexible as virtually any supervised learning algorithms can be used. We applied this approach to identify repositioning opportunities for schizophrenia as well as depression and anxiety disorders. We applied various state-of-the-art machine learning (ML) approaches for prediction, including deep neural networks, support vector machines (SVM), elastic net, random forest and gradient boosted machines. The performance of the five approaches did not differ substantially, with SVM slightly outperformed the others. However, methods with lower predictive accuracy can still reveal literature-supported candidates that are of different mechanisms of actions.
    [Show full text]
  • (ESI) for Integrative Biology. This Journal Is © the Royal Society of Chemistry 2017
    Electronic Supplementary Material (ESI) for Integrative Biology. This journal is © The Royal Society of Chemistry 2017 Table 1 Enriched GO terms with p-value ≤ 0.05 corresponding to the over-expressed genes upon perturbation with the lung-toxic compounds. Terms with corrected p-value less than 0.001 are shown in bold. GO:0043067 regulation of programmed GO:0010941 regulation of cell death cell death GO:0042981 regulation of apoptosis GO:0010033 response to organic sub- stance GO:0043068 positive regulation of pro- GO:0010942 positive regulation of cell grammed cell death death GO:0006357 regulation of transcription GO:0043065 positive regulation of apop- from RNA polymerase II promoter tosis GO:0010035 response to inorganic sub- GO:0043066 negative regulation of stance apoptosis GO:0043069 negative regulation of pro- GO:0060548 negative regulation of cell death grammed cell death GO:0016044 membrane organization GO:0042592 homeostatic process GO:0010629 negative regulation of gene ex- GO:0001568 blood vessel development pression GO:0051172 negative regulation of nitrogen GO:0006468 protein amino acid phosphoryla- compound metabolic process tion GO:0070482 response to oxygen levels GO:0045892 negative regulation of transcrip- tion, DNA-dependent GO:0001944 vasculature development GO:0046907 intracellular transport GO:0008202 steroid metabolic process GO:0045934 negative regulation of nucle- obase, nucleoside, nucleotide and nucleic acid metabolic process GO:0006917 induction of apoptosis GO:0016481 negative regulation of transcrip- tion GO:0016125 sterol metabolic process GO:0012502 induction of programmed cell death GO:0001666 response to hypoxia GO:0051253 negative regulation of RNA metabolic process GO:0008203 cholesterol metabolic process GO:0010551 regulation of specific transcrip- tion from RNA polymerase II promoter 1 Table 2 Enriched GO terms with p-value ≤ 0.05 corresponding to the under-expressed genes upon perturbation with the lung-toxic compounds.
    [Show full text]
  • Effect of Aqueous Extract of Triclisia Dictyophylla on Induced Depression in Mice
    Page 01 to 11 Current Opinions in Neurological Science ISSN: 2575-5447 Research Article Volume 5 Issue 1 • 2020 Effect of Aqueous Extract of Triclisia Dictyophylla on Induced Depression in Mice AYISSI MBOMO Rigobert-Espoir1*, ABOUEM A Zintchem Auguste2, MOTO OKOMOLO Fleur Clarisse1, NANGA Léopold Didier3, NGOA MANGA Elisabeth Sylvie3, NGO BUM Elisabeth4 1Animal Physiology Laboratory, Department of Biological Sciences, Higher Teacher’s Training College, University of Yaoundé I, Cameroon 2Organic Chemistry Laboratory, Department of Chemistry, Higher Teacher’s Training College, University of Yaoundé I, Cameroon 3Animal Physiology Laboratory, Department of Animal Biology, University of Yaoundé I, Cameroon 4Animal Physiology Laboratory, Department of Biological Sciences, Faculty of Sciences, University of Ngaoundéré, Cameroon Received : January 05, 2020 Published : February *Corresponding Author: AYISSI MBOMO Rigobert Espoir, Senior Lecturer, Copyright © All rights are reserved Higher Teacher Training College, University of Yaoundé I, PoBox 47 Yaounde, 18, 2020 by Ayissi Mbomo Rigobert Espoir., et al. Cameroon Abstract Depression affect between 2 and 5% of world’s population, the conventional medicine provides a wide variety of antidepressants not safe for patients. We assessed antidepressant properties of Triclisia dictyophylla using animal models of depression including Forced Swimming Test (FST), Tail Suspension Test (TST) and anhedonia test. Five groups of six animals each were fed-up with distilled water, imipramine and doses 50, 100, 150 mg/kg. We then considered within FST and TST, duration of immobility (TI) and time of the immobility occurrence. During the anhedonia test, we measured the variation of sugar water consumption and body mass variation. Four doses of the plant The 50, 100, 150 and 300 mg/kg were used to assess the acute toxicity.
    [Show full text]
  • Computational Drug Repositioning and Elucidation of Mechanism of Action of Compounds Against SARS-Cov-2
    Computational Drug Repositioning and Elucidation of Mechanism of Action of Compounds against SARS-CoV-2 Francesco Napolitano1 Gennaro Gambardella2,3 Diego Carrella2 Xin Gao1 Diego di Bernardo2,3 1Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia. 2Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA) 80078, Italy 3Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy. Correspondance: [email protected] Abstract The COVID-19 crisis called for rapid reaction from all the fields of biomedical research. Traditional drug development involve time consum- ing pipelines that conflict with the urgence of identifying effective thera- pies during a health and economic emergency. Drug repositioning, that is the discovery of new clinical applications for drugs already approved for different therapeutic contexts, could provide an effective shortcut to bring COVID-19 treatments to the bedside in a timely manner. More- over, computational approaches can help accelerate the process even fur- ther. Here we present the application of different software tools based on transcriptomics data to identify drugs that are potentially able to coun- teract SARS-CoV-2 infection and also to provide insights on their mode of action. We believe that HDAC inhibitors warrant further investiga- tion. In addition, we found that the DNA Mismatch repair pathway is strongly modulated by drugs with experimental in vitro activity against SARS-CoV-2 infection. 1 Introduction Drug repositioning or drug repurposing aims to find a new clinical applica- tion for a drug already in use but for a different purpose.
    [Show full text]
  • Computational Drug Repositioning and Elucidation of Mechanism Of
    Computational Drug Repositioning and Elucidation of Mechanism of Action of Compounds against SARS-CoV-2 Francesco Napolitano1, Gennaro Gambardella2,3, Xin Gao1, and Diego di Bernardo2,3,* 1Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia 2Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA) 80078, Italy and 3Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy. *[email protected] ABSTRACT The COVID-19 crisis called for rapid reaction from all the fields of biomedical research. Traditional drug development involves time consuming pipelines that conflict with the urgence of identifying effective therapies during a health and economic emergency. Drug repositioning, that is the discovery of new clinical applications for drugs already approved for different therapeutic contexts, could provide an effective shortcut to bring COVID-19 treatments to the bedside in a timely manner. Moreover, computational approaches can help accelerate the process even further. Here we present the application of computational drug repositioning tools based on transcriptomics data to identify drugs that are potentially able to counteract SARS-CoV-2 infection, and also to provide insights on their mode of action. We believe that mucolytics and HDAC inhibitors warrant further investigation. In addition, we found that the DNA Mismatch repair pathway is strongly modulated by drugs with experimental in vitro activity against SARS-CoV-2 infection. Both full results and methods are publicly available. 1 Introduction Drug repositioning or drug repurposing aims to find a new clinical application for a drug already in use but for a different purpose.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,916,910 Lai (45) Date of Patent: Jun
    USOO591.6910A United States Patent (19) 11 Patent Number: 5,916,910 Lai (45) Date of Patent: Jun. 29, 1999 54 CONJUGATES OF DITHIOCARBAMATES Middleton et al., “Increased nitric oxide synthesis in ulcer WITH PHARMACOLOGICALLY ACTIVE ative colitis” Lancet, 341:465-466 (1993). AGENTS AND USES THEREFORE Miller et al., “Nitric Oxide Release in Response to Gut Injury Scand. J. Gastroenterol., 264:11-16 (1993). 75 Inventor: Ching-San Lai, Encinitas, Calif. Mitchell et al., “Selectivity of nonsteroidal antiinflamatory drugs as inhibitors of constitutive and inducible cyclooxy 73 Assignee: Medinox, Inc., San Diego, Calif. genase” Proc. Natl. Acad. Sci. USA, 90:11693–11697 (1993). 21 Appl. No.: 08/869,158 Myers et al., “Adrimaycin: The Role of Lipid Peroxidation in Cardiac Toxicity and Tumor Response' Science, 22 Filed: Jun. 4, 1997 197:165-167 (1977). 51) Int. Cl. ...................... C07D 207/04; CO7D 207/30; Onoe et al., “Il-13 and Il-4 Inhibit Bone Resorption by A61K 31/27; A61K 31/40 Suppressing Cyclooxygenase-2-Dependent ProStaglandin 52 U.S. Cl. .......................... 514/423: 514/514; 548/564; Synthesis in Osteoblasts' J. Immunol., 156:758–764 548/573; 558/235 (1996). 58 Field of Search ..................................... 514/514, 423; Reisinger et al., “Inhibition of HIV progression by dithio 548/565,573; 558/235 carb” Lancet, 335:679–682 (1990). Schreck et al., “Dithiocarbamates as Potent Inhibitors of 56) References Cited Nuclear Factor KB Activation in Intact Cells' J. Exp. Med., 175:1181–1194 (1992). U.S. PATENT DOCUMENTS Slater et al., “Expression of cyclooxygenase types 1 and 2 in 4,160,452 7/1979 Theeuwes ..............................
    [Show full text]
  • Potassium Channel Kcsa
    Potassium Channel KcsA Potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions. Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly and selectively. Biologically, these channels act to set or reset the resting potential in many cells. In excitable cells, such asneurons, the delayed counterflow of potassium ions shapes the action potential. By contributing to the regulation of the action potential duration in cardiac muscle, malfunction of potassium channels may cause life-threatening arrhythmias. Potassium channels may also be involved in maintaining vascular tone. www.MedChemExpress.com 1 Potassium Channel Inhibitors, Agonists, Antagonists, Activators & Modulators (+)-KCC2 blocker 1 (3R,5R)-Rosuvastatin Cat. No.: HY-18172A Cat. No.: HY-17504C (+)-KCC2 blocker 1 is a selective K+-Cl- (3R,5R)-Rosuvastatin is the (3R,5R)-enantiomer of cotransporter KCC2 blocker with an IC50 of 0.4 Rosuvastatin. Rosuvastatin is a competitive μM. (+)-KCC2 blocker 1 is a benzyl prolinate and a HMG-CoA reductase inhibitor with an IC50 of 11 enantiomer of KCC2 blocker 1. nM. Rosuvastatin potently blocks human ether-a-go-go related gene (hERG) current with an IC50 of 195 nM. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 1 mg, 5 mg (3S,5R)-Rosuvastatin (±)-Naringenin Cat. No.: HY-17504D Cat. No.: HY-W011641 (3S,5R)-Rosuvastatin is the (3S,5R)-enantiomer of (±)-Naringenin is a naturally-occurring flavonoid.
    [Show full text]
  • Natural Modulators of Large-Conductance Calcium
    Antonio Nardi1 Vincenzo Calderone2 Natural Modulators of Large-Conductance Silvio Chericoni3 Ivano Morelli3 Calcium-Activated Potassium Channels Review Abstract wards identifying new BK-modulating agents is proceeding with great impetus and is giving an ever-increasing number of Large-conductance calcium-activated potassium channels, also new molecules. Among these, also a handsome number of natur- known as BK or Maxi-K channels, occur in many types of cell, in- al BK-modulator compounds, belonging to different structural cluding neurons and myocytes, where they play an essential role classes, has appeared in the literature. The goal of this paper is in the regulation of cell excitability and function. These proper- to provide a possible simple classification of the broad structural ties open a possible role for BK-activators also called BK-open- heterogeneity of the natural BK-activating agents terpenes, phe- ers) and/or BK-blockers as effective therapeutic agents for differ- nols, flavonoids) and blockers alkaloids and peptides), and a ent neurological, urological, respiratory and cardiovascular dis- concise overview of their chemical and pharmacological proper- eases. The synthetic benzimidazolone derivatives NS004 and ties as well as potential therapeutic applications. NS1619 are the pioneer BK-activators and have represented the reference models which led to the design of several novel and Key words heterogeneous synthetic BK-openers, while very few synthetic Natural products ´ potassium channels ´ large-conductance cal- BK-blockers have been reported. Even today, the research to- cium-activated BK channels ´ BK-activators ´ BK-blockers 885 Introduction tracellular Ca2+ and membrane depolarisation, promoting a mas- sive outward flow of K+ ions and leading to a membrane hyper- Among the different factors exerting an influence on the activity polarisation, i.e., to a stabilisation of the cell [1].
    [Show full text]