DOCSLIB.ORG

Supplemental Table 3. Individual Drug Predictions by CMAP Analysis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplemental Table 3. Individual Drug Predictions by CMAP Analysis Supplemental Table 3. Individual drug predictions by CMAP analysis. Correlationc Drug Familya Drug Degreeb 595 638 589 Proteasome inhibitors and UPS disulfiram ++ + + + modulators MG-262 +++ np + + mometasone ++ np + + NFκB inhibitors 15-delta prostaglandin J2 ++ + + + thiostrepton ++ + + np parthenolide ++ + + np withaferin A ++ + + + HSP90 inhibitors geldanamycin ++ + + np alvespimycin ++ + np + monorden + + np + tanespimycin + + np np Protein synthesis inhibitors puromycin +++ + + + anisomycin +++ np + + emetine ++ np + + cephaeline +++ np + + cicloheximide ++ + + + CDK/TopoI/TopoII/Cell cycle doxorubicin – – – np - - inhibitors resveratrol ++ + np np camptothecin – – – np - np ellipticine – – np - np etoposide – – np - np mitoxantrone – – np - np harmine – – np np - luteolin – – np np - staurosporine – np np - Sodium/calcium modulators and tetrandrine + + + + calcium channel blockers gossypol ++ + + + econazole ++ + + np perhexiline ++ + + np clomifene ++ + + np bepridil ++ + + np felodipine + np + + nitrendipine – – - np np cyproheptadine ++ + np np Na+/K+ - ATPase membrane helveticoside ++ np + + pump inhibitors lanatoside C ++ np + + digoxin ++ np + + digitoxigenin ++ np + + digoxigenin + np np + strophanthidin + np np + ouabain + np np + Antihistamines and terfenadine +++ + + + Anticholinergics astemizole ++ + + np proadifen ++ + np + spiperone ++ np + + atropine – – np np - mefloquine ++ + np + clemastine ++ np + np Microtubule inhibitors mebendazole ++ + + np nocodazole ++ + np + fenbendazole ++ + + np Alkylating agents semustine ++ + + + lomustine ++ + + np PI3K inhibitors LY-294002 ++ + np np HDAC inhibitors trichostatin A ++ + np np vorinostat ++ + np np rifabutin ++ + np np scriptaid ++ + np np valproic acid ++ + np np Antipsychotics thioridazine ++ + + np prochlorperazine ++ + + np pimozide ++ + + np fluphenazine ++ + + np metergoline ++ + np np chlorcyclizine + + + np trifluoperazine ++ + + np metixene ++ np np + cloperastine ++ + np np perphenazine ++ + np np thioproperazine ++ + np np Antidepressants desipramine ++ + + np doxepin ++ + np np norcyclobenzaprine ++ + np np imipramine ++ + np np Antivirals mycophenolic acid – – np - - methotrexate – np - np aDrugs families determined from previous literature (1). bIndicates the degree to which a drug is positively or negatively correlated (by correlation score output from CMAP) calculated as the average correlation score across the 3 lines where: |0- 0.33| = +/-; |0.34-0.66| = ++/--; |0.67-1| = +++/---. cOutput given by CMAP indicating the relatedness of the input profile to the database profile where “–“ is a strong opposite response and “+” is a strong similar response by gene expression profiling. “np” indicates that no prediction was made for this drug in this cell line. All prediction were significant with a p < 0.05. Reference 1. Iorio F, Bosotti R, Scacheri E, Belcastro V, Mithbaokar P, Ferriero R, et al. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proceedings of the National Academy of Sciences of the United States of America. 2010;107:14621-6. .
Load more

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]
  • Basic Quant GCMS
    Harris County Institute of Forensic Sciences Section: Toxicology Approved By: Toxicology Manager Document Type: GC & GC/MS Procedure No.: TOX07.3005 Title: Quantitation of basic drugs by gas chromatography / mass spectrometry Rev.:15 1.0 Purpose 1.1 This document describes the procedures used by the Toxicology Laboratory to quantitate basic drugs using gas chromatography/mass spectrometry. 1.2 Biological specimens are basified to the moderately alkaline pH 9 at which basic compounds are in an unionized form and are soluble in an organic solvent. After liquid/liquid extraction, the organic layer is separated and the compound X is back extracted into 2 N HCl. The acid layer is then made alkaline and compound X is re-extracted into an organic solvent. 2.0 Scope 2.1 The assay is appropriate for quantitation of any basic compound (X) in blood including serum and plasma, urine, bile, stomach contents or tissue homogenates. 3.0 Definitions and Abbreviations 3.1 No method-specific or non-standard terms are used in this procedure. 4.0 Materials 4.1 Instruments and Equipment 4.1.1 13 x 100 mm screw top tubes and caps 4.1.2 Mixer 4.1.3 Rocker 4.1.4 Centrifuge 4.1.5 Transfer pipettes 4.1.6 Autosampler vials and rubber septum caps 4.1.7 Autosampler vial inserts 4.1.8 Vial crimper 4.1.9 100uL syringe 4.1.10 GC/MS Uncontrolled4.2 Reagents Copy 4.2.1 Ammonium Hydroxide Reagent Grade 4.2.2 n-Butyl chloride (chlorobutane) HPLC Grade 4.2.3 Saturated Sodium Borate Buffer, pH 9.3 A.
    [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]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0024365A1 Vaya Et Al
    US 2006.0024.365A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0024365A1 Vaya et al. (43) Pub. Date: Feb. 2, 2006 (54) NOVEL DOSAGE FORM (30) Foreign Application Priority Data (76) Inventors: Navin Vaya, Gujarat (IN); Rajesh Aug. 5, 2002 (IN)................................. 699/MUM/2002 Singh Karan, Gujarat (IN); Sunil Aug. 5, 2002 (IN). ... 697/MUM/2002 Sadanand, Gujarat (IN); Vinod Kumar Jan. 22, 2003 (IN)................................... 80/MUM/2003 Gupta, Gujarat (IN) Jan. 22, 2003 (IN)................................... 82/MUM/2003 Correspondence Address: Publication Classification HEDMAN & COSTIGAN P.C. (51) Int. Cl. 1185 AVENUE OF THE AMERICAS A6IK 9/22 (2006.01) NEW YORK, NY 10036 (US) (52) U.S. Cl. .............................................................. 424/468 (22) Filed: May 19, 2005 A dosage form comprising of a high dose, high Solubility active ingredient as modified release and a low dose active ingredient as immediate release where the weight ratio of Related U.S. Application Data immediate release active ingredient and modified release active ingredient is from 1:10 to 1:15000 and the weight of (63) Continuation-in-part of application No. 10/630,446, modified release active ingredient per unit is from 500 mg to filed on Jul. 29, 2003. 1500 mg, a process for preparing the dosage form. Patent Application Publication Feb. 2, 2006 Sheet 1 of 10 US 2006/0024.365A1 FIGURE 1 FIGURE 2 FIGURE 3 Patent Application Publication Feb. 2, 2006 Sheet 2 of 10 US 2006/0024.365A1 FIGURE 4 (a) 7 FIGURE 4 (b) Patent Application Publication Feb. 2, 2006 Sheet 3 of 10 US 2006/0024.365 A1 FIGURE 5 100 ov -- 60 40 20 C 2 4.
    [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]
  • ECO Cup One Step Drug Test Forensic Insert
    paranoia, hallucinations, and psychotic behavior. The effects of Amphetamines generally last 2-4 unconsciousness. hours following use, and the drug has a half-life of 4-24 hours in the body. About 30% of Cocaine is often self-administered by nasal inhalation, intravenous injection and free-base Amphetamines are excreted in the urine in unchanged form, with the remainder as hydroxylated smoking. It is excreted in the urine in a short time primarily as Benzoylecgonine. 1.2 and deaminated derivatives. Benzoylecgonine, a major metabolite of cocaine, has a longer biological half-life (5-8 hours) than 2 The ECO CUP™ One Step Drug Test yields a positive result when the concentration of Amphetamine cocaine (0.5-1.5 hours), and can generally be detected for 24-48 hours after cocaine exposure. in urine exceeds 1,000 ng/mL. This is the suggested screening cut-off for positive specimens The ECO CUP™ One Step Drug Test yields a positive result when the concentration of Benzoylecgonine set by the Substance Abuse and Mental Health Services Administration (SAMHSA, USA).3 in urine exceeds 300 ng/mL. This is the suggested screening cut-off for positive specimens set by One Step Drug Test the Substance Abuse and Mental Health Services Administration (SAMHSA, USA). 3 Package Insert for Multi Drug Screen Test Cup AMPHETAMINE (AMP 500) COCAINE (COC 150) This Instruction Sheet is for testing of any combination of the following drugs: See AMPHETAMINE (AMP 1000) for the summary. See COCAINE (COC 300) for the summary. AMP/BAR/BZO/BUP/COC/THC/MTD/mAMP/MDMA/MOR/OPI/OXY/PCP/PPX/TCA/EDDP/6-ACM/ETG The ECO CUP™ One Step Drug Test yields a positive result when the concentration of The ECO CUP™ One Step Drug Test yields a positive result when the concentration of Including Adulterant Tests (Specimen Validity Tests) for: Amphetamine in urine exceeds 500 ng/mL.
    [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]
  • Alltech® Drug Standards for the Forensic, Clinical & Pharmaceutical Industries OH
    Alltech® Drug Standards For the Forensic, Clinical & Pharmaceutical Industries OH H3C H H H3C H HO Catalog #505B Our Company Welcome to the Grace's Alltech® Drug Standards Catalog W. R. Grace has manufactured high-quality silica for over 150 years. Grace has been behind the scenes for the past 30 years supplying silica to the chromatography industry. Now we’re in the forefront moving beyond silica, developing and delivering innovative complementary products direct to the customer. Grace Davison Discovery Sciences was founded on Grace’s core strength as a premier manufacturer of differentiated media for SPE, Flash, HPLC, and Process chromatography. This core competency is further enhanced by bringing seven well-known global separations companies together, creating a powerful new single source for all your chromatography needs. A Full Portfolio of Chromatography Products to Support Drug Standards: • HPLC Columns • HPLC Accessories • Flash Products • TLC Products • GC Columns • GC Accessories • SPE and Filtration • Equipment • Syringes • Tubing • Vials For complete details, download the Chromatography Essentials catalog from the Grace web site or contact your customer service representative. Alltech - Part of the Grace Family of Products In 2004, Alltech Associates Inc. was acquired by Grace along with the Alltech® Drug Standards product line. Through investment in research and strategic acquisitions, Grace has expanded our product range and global reach while drawing upon the support of the Grace corporate infrastructure and more than 6000 employees globally to support scientific research and analysis worldwide. With key manufacturing sites in North and South America, Europe, and Asia, plus an extensive international sales and distribution network, separation scientists throughout the world can count on timely delivery and expert local technical service.
    [Show full text]
  • The Sigma1 Protein As a Target for the Non-Genomic Effects of Neuro(Active)Steroids: Molecular, Physiological, and Behavioral Aspects François P
    J Pharmacol Sci 100, 93 – 118 (2006) Journal of Pharmacological Sciences ©2006 The Japanese Pharmacological Society Critical Review The Sigma1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids: Molecular, Physiological, and Behavioral Aspects François P. Monnet1 and Tangui Maurice2,* 1Unité 705 de l’Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 7157 du Centre National de la Recherche Scientifique, Université de Paris V et VII, Hôpital Lariboisière-Fernand Widal, 2, rue Ambroise Paré, 75475 Paris cedex 10, France 2Unité 710 de l’Institut National de la Santé et de la Recherche Médicale, Ecole Pratique des Hautes Etudes, Université de Montpellier II, cc 105, place Eugène Bataillon, 34095 Montpellier cedex 5, France Received December 15, 2005 Abstract. Steroids synthesized in the periphery or de novo in the brain, so called ‘neuro- steroids’, exert both genomic and nongenomic actions on neurotransmission systems. Through rapid modulatory effects on neurotransmitter receptors, they influence inhibitory and excitatory neurotransmission. In particular, progesterone derivatives like 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) are positive allosteric modulators of the γ-aminobutyric acid type A (GABAA) receptor and therefore act as inhibitory steroids, while pregnenolone sulphate (PREGS) and dehydroepiandrosterone sulphate (DHEAS) are negative modulators of the GABAA receptor and positive modulators of the N-methyl-D-aspartate (NMDA) receptor, therefore acting as excitatory neurosteroids. Some steroids also interact with atypical proteins, the sigma (σ) receptors. Recent studies particularly demonstrated that the σ1 receptor contributes effectively to their pharmaco- logical actions. The present article will review the data demonstrating that the σ1 receptor binds neurosteroids in physiological conditions.
    [Show full text]