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Zuranolone | Medchemexpress
Inhibitors Product Data Sheet Zuranolone • Agonists Cat. No.: HY-103040 CAS No.: 1632051-40-1 Molecular Formula: C₂₅H₃₅N₃O₂ • Molecular Weight: 409.56 Screening Libraries Target: GABA Receptor Pathway: Membrane Transporter/Ion Channel; Neuronal Signaling Storage: Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month SOLVENT & SOLUBILITY In Vitro DMSO : 100 mg/mL (244.16 mM; Need ultrasonic) H2O : < 0.1 mg/mL (insoluble) Mass Solvent 1 mg 5 mg 10 mg Concentration Preparing 1 mM 2.4416 mL 12.2082 mL 24.4164 mL Stock Solutions 5 mM 0.4883 mL 2.4416 mL 4.8833 mL 10 mM 0.2442 mL 1.2208 mL 2.4416 mL Please refer to the solubility information to select the appropriate solvent. In Vivo 1. Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline Solubility: 2.5 mg/mL (6.10 mM); Suspended solution; Need ultrasonic 2. Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (6.10 mM); Clear solution 3. Add each solvent one by one: 10% DMSO >> 90% corn oil Solubility: ≥ 2.5 mg/mL (6.10 mM); Clear solution 4. Add each solvent one by one: 5% DMSO >> 40% PEG300 >> 5% Tween-80 >> 50% saline Solubility: 2.5 mg/mL (6.10 mM); Suspended solution; Need ultrasonic 5. Add each solvent one by one: 5% DMSO >> 95% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (6.10 mM); Clear solution BIOLOGICAL ACTIVITY Description Zuranolone is an orally active and potent neuroactive steroid positive allosteric modulator of GABAA receptor, with EC50s of [1] 296 and 163 nM for α1β2γ2 and α4β3δ GABAA receptors, respectively . -
Présentation HJ
Conflits d’intérêts Astra-Zeneca, Janssen, Abacus international, Laboratoire ETAP, Institut Pasteur. Dr Hervé JAVELOT Pharmacien PH Etablissement Public de Santé Alsace Nord Service Pharmacie 141 avenue de Strasbourg 67 170 BRUMATH Tél. : 03 88 64 61 70 Fax : 03 88 64 61 58 Mail : [email protected] Perspectives dans la psychopharmacologie de l’anxiété et de la dépression Hervé JAVELOT Etablissement Public de Santé Alsace Nord Perspectives dans la psychopharmacologie de l’anxiété et de la dépression Traitements des troubles anxio-dépressifs. Les perspectives. ◦ L’axe GABAergique…éternellement prometteur ? ◦ L’incontournable théorie « monoaminergique »… ◦ Des théories alternatives à suivre … Traitements des troubles anxio-dépressifs. Contexte : ◦ XXI ème siècle : Le « siècle de la dépression » s’installe ? (Hardeveld et al., 2010) L’« ère de l’angoisse » s’affirme ? (Auden, 1947) ◦ Prévalence au cours de la vie : 16 à 17% pour la dépression, 17 à 18% pour les troubles anxieux Co-morbidité des 2 troubles dans 20 à 40% des cas (Antony, 2011 ; Depping et al., 2010 ; Hardeveld et al., 2010 ; Huppert, 2009) Auden WH (1947). The Age of Anxiety: A Baroque Eclogue. Random House: New York. Hardeveld F, Spijker J, De Graaf R, Nolen WA, Beekman AT. Prevalence and predictors of recurrence of major depressive disorder in the adult population. Acta Psychiatr Scand. 2010;122(3):184-91. Antony MM. Recent advances in the treatment of anxiety disorders. Canadian Psychology 2011;52(1), 10-19. Depping AM, Komossa K, Kissling W, Leucht S. Second-generation antipsychotics for anxiety disorders. Cochrane Database Syst Rev. 2010;(12):CD008120. Huppert JD. Anxiety disorders and depression comorbidity. -
A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling
biomolecules Review Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling Christopher L. Cioffi Departments of Basic and Clinical Sciences and Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA; christopher.cioffi@acphs.edu; Tel.: +1-518-694-7224 Abstract: Among the myriad of cellular and molecular processes identified as contributing to patho- logical pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread + − interest as a potential class of novel analgesics. The GlyTs are Na /Cl -dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a Citation: Cioffi, C.L. Inhibition of possible mechanism -
Directvote Election: Candidate Bios
DirectVote Election: Candidate Bios Councilor Slot 2 Your Voting Status: Select 0 to 1 from below. Selected: 0 Vote For: Lisa Monteggia Lisa Monteggia Administrative Accomplishments: I have been involved in numerous administrative roles at UT Southwestern Medical Center, including Faculty Search Committees, membership in the Animal Resource Center advisory committee, Institutional Animal Care and Use Committee, Graduate Student Admissions committee, as well as the development of the Behavioral Core Facility. These opportunities have provided me with the skills and experience to deal with the needs and operations of basic science —in particular animal research— in a complex medical school campus. Degree, Institute, Year Earned: BS, University of Illinois-Urbana, 1989 MS, University of Illinois-Urbana, 1991 PhD, The Chicago Medical School, 1998 Postdoctoral fellow, Yale University, 1998-2000 Research Areas: My research interest is the molecular and cellular mechanisms underlying psychiatric disorders and neuropsychiatric treatment strategies. My laboratory studies two critical areas of translational brain research, mechanisms underlying antidepressant action and synaptic alterations that lead to the pathophysiology of the Rett syndrome. Our focus is on the role of synaptic plasticity mechanisms that may underlie these disorders and suggest potential targets for therapeutics. Current Position(s) at Your Current Institution: Ginny and John Eulich Professorship in Autism Spectrum Disorders, Professor of Neuroscience, UT Southwestern Medical -
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol Drug Abuse and Mental Health Administration Pharmacology and Toxicology of Amphetamine and Related Designer Drugs Editors: Khursheed Asghar, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Errol De Souza, Ph.D. Addiction Research Center National Institute on Drug Abuse NIDA Research Monograph 94 1989 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 Pharmacology and Toxicology of Amphetamine and Related Designer Drugs ACKNOWLEDGMENT This monograph is based upon papers and discussion from a technical review on pharmacology and toxicology of amphetamine and related designer drugs that took place on August 2 through 4, 1988, in Bethesda, MD. The review meeting was sponsored by the Biomedical Branch, Division of Preclinical Research, and the Addiction Research Center, National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other matieral in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. -
Targeting Glycine Reuptake in Alcohol Seeking and Relapse
JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. TITLE PAGE Targeting Glycine Reuptake in Alcohol Seeking and Relapse Valentina Vengeliene, Martin Roßmanith, Tatiane T. Takahashi, Daniela Alberati, Berthold Behl, Anton Bespalov, Rainer Spanagel Downloaded from The primary laboratory of origin: Institute of Psychopharmacology, Central Institute of jpet.aspetjournals.org Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; at ASPET Journals on September 30, 2021 VV, MR, TTT, RS: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; DA: Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, CH-4070 Basel, Switzerland; BB, AB: Department of Neuroscience Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; AB: Department of Psychopharmacology, Pavlov Medical University, St Petersburg, Russia JPET #244822 JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. RUNNING TITLE GlyT1 in Alcohol Seeking and Relapse Corresponding author with complete address: Valentina Vengeliene, Institute of Psychopharmacology, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany Email: [email protected], phone: +49-621-17036261; fax: +49-621- Downloaded from 17036255 jpet.aspetjournals.org The number of text pages: 33 Number of tables: 0 Number of figures: 6 Number of references: 44 at ASPET Journals on September 30, 2021 Number of words in the Abstract: 153 Number of words in the Introduction: 729 Number of words in the Discussion: 999 A recommended section assignment to guide the listing in the table of content: Drug Discovery and Translational Medicine 2 JPET #244822 JPET Fast Forward. -
Treatment of Schizophrenia Course Director: Philip Janicak, M.D
S6735- Treatment of Schizophrenia Course Director: Philip Janicak, M.D. #APAAM2016 Saturday, May 14, 2016 Marriott Marquis - Marquis Ballroom D psychiatry.org/ annualmeetingS4637 ANNUAL MEETING May 14-18, 2016 • Atlanta Reference • Janicak PG, Marder SR, Tandon R, Goldman M (Eds.). Schizophrenia: Recent Advances in Diagnosis and Treatment. New York, NY: Springer; 2014. Schizophrenia: Recent Diagnostic Advances, Neurobiology, and the Neuropharmacology of Antipsychotic Drug Therapy Rajiv Tandon, MD Professor of Psychiatry University of Florida College of Medicine Gainesville, Florida Annual Meeting of the American Psychiatric Association New York, New York May 3–7, 2014 Disclosure Information MEMBER, WPA PHARMACOPSYCHIATRY SECTION MEMBER, DSM-5 WORKGROUP ON PSYCHOTIC DISORDERS A CLINICIAN AND CLINICAL RESEARCHER Pharmacological Treatment of Any Disease • Know the Disease that you are treating • Nature; Treatment targets; Treatment goals; • Know the Treatments at your disposal • What they do; How they compare; Costs; • Principles of Treatment • Measurement-based; Targeted; Individualized Program Outline • Nature and Definition of psychosis? • Clinical description • What is wrong in psychotic illness • Dimensions of Psychopathology • Neurobiological Abnormalities • Mechanisms underlying antipsychotic effects? • What contributes to Efficacy • Basis of Side-effect differences 5 Challenges in DSM-IV Construct of Psychotic Disorders ♦ Indistinct Boundaries ♦ With Other Disorders (eg., with OCD) ♦ Within Group of Psychotic Disorders (eg. between -
Essential Role of Brain-Derived Neurotrophic Factor in Adult Hippocampal Function
Essential role of brain-derived neurotrophic factor in adult hippocampal function Lisa M. Monteggia*†, Michel Barrot*, Craig M. Powell*, Olivier Berton*, Victor Galanis*, Terry Gemelli*, Sven Meuth*, Andreas Nagy‡, Robert W. Greene*, and Eric J. Nestler* *Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070; and ‡Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5 Edited by Floyd E. Bloom, The Scripps Research Institute, La Jolla, CA, and approved May 27, 2004 (received for review March 26, 2004) Brain-derived neurotrophic factor (BDNF) regulates neuronal de- specific enolase–tetracycline transcriptional activator (NSE– velopment and function. However, it has been difficult to discern tTA) line are on a BL6͞SJL ϫ ICR background, the TetOp-Cre its role in the adult brain in influencing complex behavior. Here, we are on an ICR background, and the floxed BDNF mice are on use a recently developed inducible knockout system to show that a BL6͞sv129 background. The NSE–tTA mice (14) and the deleting BDNF in broad forebrain regions of adult mice impairs TetOp-Cre mice (15, 16) were maintained as homozygotes then hippocampal-dependent learning and long-term potentiation. We crossed to generate the bigenic mice. The floxed LacZ reporter use the inducible nature of this system to show that the loss of mice (17) or floxed BDNF mice (13) were then crossed with the BDNF during earlier stages of development causes hyperactivity bigenic NSE–tTA͞TetOp-Cre mice to generate the inducible and more pronounced hippocampal-dependent learning deficits. KO mice. All experiments were performed on littermates de- We also demonstrate that the loss of forebrain BDNF attenuates rived from this mating paradigm to ensure analysis by matched the actions of desipramine, an antidepressant, in the forced swim controls. -
View Presentation
Investor Presentation June 2020 Safe Harbor Statement • The slides presented today and the accompanying oral presentations contain forward-looking statements, which may be identified by the use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “opportunity”, “goal”, “potential,” or “continue,” and other similar expressions. • Forward-looking statements in this presentation include statements regarding: our plans and expectations for ZULRESSO, including our revenue expectations and the factors that may impact revenues; our expectations as to the development and regulatory path forward and filing requirements for zuranolone; our development plans, goals and strategy for our product candidates and the potential results of our development efforts; the anticipated timing of clinical trial initiation and reporting of results, including our belief as to our ability to mitigate the possible impact of the COVID-19 pandemic on our clinical development timelines; the potential profile and benefit of our product candidates; our belief in the potential of our product candidates in various indications; the estimated number of patients with the disorders and diseases we are studying or plan to study; our financial expectations, including with respect to year-end cash; our belief that existing cash will support operations into 2022; and our expectations as to the goals, opportunity and potential for our business. • These forward-looking statements are neither promises -
Zuranolone—An Investigational Oral Neuroactive Steroid and Positive
Expert Interview Psychiatric Disorders Zuranolone—An Investigational Oral Neuroactive Steroid and Positive Allosteric Modulator of GABA Type A Receptors for Postpartum Depression and Major Depressive Disorder Handan Gunduz-Bruce Sage Therapeutics, Inc., Cambridge, MA, USA Handan Gunduz-Bruce Handan Gunduz-Bruce is Senior Medical Director at Sage Therapeutics, Inc. and Assistant Clinical Professor of Psychiatry at Yale School of Medicine. She received her medical degree from the Istanbul Medical Faculty in 1991 and then completed her residency in psychiatry, followed by a fellowship in clinical neuroscience at the Long Island Jewish Medical Center of Albert Einstein College of Medicine. Earlier in her academic career, Dr. Gunduz-Bruce’s research focused on the longitudinal course and pharmacological treatment of schizophrenia. Her later research included pathophysiology studies of schizophrenia and depression with a focus on the N-methyl-D-aspartate (NMDA) receptor function and GABAergic mechanisms using electrophysiological, imaging and biomarker approaches. More recently, she received her MBA degree in Leadership in Healthcare from Yale School of Management. Since the beginning of her tenure at Sage Therapeutics, Dr. Gunduz-Bruce has contributed to the approval of ZULRESSOTM, the first pharmacological treatment for postpartum depression in adults, and continues to oversee the development of zuranolone, an investigational oral neuroactive steroid and positive allosteric modulator of GABAA receptors, for postpartum depression and major -
Horizon Scanning Status Report Volume 2, Issue 1 March 2020
PCORI Health Care Horizon Scanning System Horizon Scanning Status Report Volume 2, Issue 1 March 2020 Prepared for: Patient-Centered Outcomes Research Institute 1828 L St., NW, Suite 900 Washington, DC 20036 Contract No. MSA-HORIZSCAN-ECRI-ENG-2018.7.12 Prepared by: ECRI Institute 5200 Butler Pike Plymouth Meeting, PA 19462 Investigators: Randy Hulshizer, MA, MS Damian Carlson, MS Christian Cuevas, PhD Andrea Druga, PA-C Marcus Lynch, PhD Misha Mehta, MS Brian Wilkinson, MA Donna Beales, MLIS Jennifer De Lurio, MS Eloise DeHaan, BS Eileen Erinoff, MSLIS Maria Middleton, MPH Diane Robertson, BA Kelley Tipton, MPH Rosemary Walker, MLIS Karen Schoelles, MD, SM Statement of Funding and Purpose This report incorporates data collected during implementation of the Patient-Centered Outcomes Research Institute (PCORI) Health Care Horizon Scanning System, operated by ECRI Institute under contract to PCORI, Washington, DC (Contract No. MSA-HORIZSCAN-ECRI-ENG- 2018.7.12). The findings and conclusions in this document are those of the authors, who are responsible for its content. No statement in this report should be construed as an official position of PCORI. An intervention that potentially meets inclusion criteria might not appear in this report simply because the Horizon Scanning System has not yet detected it or it does not yet meet inclusion criteria outlined in the PCORI Health Care Horizon Scanning System: Horizon Scanning Protocol and Operations Manual. Inclusion or absence of interventions in the horizon scanning reports will change over time as new information is collected; therefore, inclusion or absence should not be construed as either an endorsement or rejection of specific interventions. -
LISA M. MONTEGGIA, Ph.D
LISA M. MONTEGGIA, Ph.D. RANK/TITLE: Barlow Family Director of the Vanderbilt Brain Institute Professor, Department of Pharmacology Address: Vanderbilt University MRBIII, Suite 7140 465 21st Avenue South Nashville, TN 37240-7933 PH: (615) 936-5483 FX: (615) 6936-3613 EM: [email protected] EDUCATION: University of Illinois, Urbana, IL – B.S.- Microbiology – 1989 University of Illinois, Urbana, IL – M.S. – Biology – 1991 The Chicago Medical School, North Chicago, IL – Ph.D. – Neuroscience – 1999 (Dr. Marina Wolf, PI) POSTDOCTORAL TRAINING: 1998-2000 Department of Psychiatry (Dr. Eric Nestler, PI) Yale University, New Haven, CT OTHER TRAINING: 1991-1994 Associate Scientist, Department of Neuroscience, Abbott Laboratories, Abbott Park, IL 1994-1998 Scientist, Department of Neuroscience, Abbott Laboratories, Abbott Park, IL ACADEMIC APPOINTMENTS: 09/2000-10/2002 Research Assistant Professor, Department of Psychiatry, UT Southwestern, Dallas, TX 10/2002-09/2009 Assistant Professor, Department of Psychiatry, UT Southwestern, Dallas, TX 09/2009-09/2013 Associate Professor (tenure), Department of Psychiatry, UT Southwestern, Dallas, TX 06/2010-06/2018 Ginny and John Eulich Professorship in Autism Spectrum Disorders 09/2013-06/2018 Professor, Department of Neuroscience, UT Southwestern, Dallas, TX 07/2018- Director, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 07/2018- Professor of Pharmacology, Vanderbilt University, Nashville, TN AWARDS/HONORS: 1985-1989 University of Illinois, Full Academic Tuition Scholarship 1991 Top 10% of Teaching Assistants for Excellence in Teaching, University of Illinois 1998-2000 NIH/NIDA Postdoctoral Training Grant, Yale University 2001 Young Investigator Award, NARSAD 2002 American College of Neuropsychopharmacology/Bristol-Myers Squibb Travel Award 2003 Developmental Neurobiology and Child Psychiatry, Otsuka Travel Award 2003 College on Problems on Drug Dependence, Center for Addictive Diseases Travel Award 2003 Young Investigator Award, NARSAD 2005 Daniel X.