DOCSLIB.ORG

Gepirone Hydrochloride Extended-Release Tablets NDA #21-164

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gepirone Hydrochloride Extended-Release Tablets NDA #21-164 Gepirone Hydrochloride Extended-Release Tablets NDA #21-164 Psychopharmacologic Drugs Advisory Committee Meeting Briefing Materials December 1, 2015 ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE WITHOUT REDACTION Fabre-Kramer Pharmaceuticals, Inc. Page ii 10/27/2015 TABLE OF CONTENTS Contents Table of Contents ............................................................................................................................ ii I. List of Tables In text .............................................................................................................. iv II. List of Figures in text ............................................................................................................. vi III. List of Abbreviations ........................................................................................................ vii 1. EXECUTIVE SUMMARY .................................................................................................... 1 2. Introduction ............................................................................................................................. 3 2.1 Medical Need for New Anti-Depressant Treatments ....................................................... 3 2.1.1 Unique Sexual Functioning Profile ........................................................................... 4 2.2 Clinical Study Challenges in Antidepressant Development ............................................ 5 2.3 Gepirone ER Formulation Characteristics ....................................................................... 6 2.4 The Unique Mechanism of Action of Gepirone ER ......................................................... 7 2.5 Gepirone ER Clinical Development and Regulatory History .......................................... 8 3. Efficacy ................................................................................................................................. 10 3.1 Overview of Clinical Studies ......................................................................................... 10 3.2 Selection of Studies for Assessment of Efficacy ........................................................... 11 3.3 Summary of Individual Interpretable Gepirone ER Studies .......................................... 13 3.3.1 Study 134001 .......................................................................................................... 13 3.3.2 Study 134002 .......................................................................................................... 13 3.3.3 Study 134023 .......................................................................................................... 13 3.3.4 Study FKGBE007 ................................................................................................... 14 3.3.5 Study FKGBE008 ................................................................................................... 14 3.3.6 Summary of Efficacy Data from Interpretable Gepirone ER Studies ..................... 14 3.4 Summary of Individual Uninterpretable Gepirone ER Studies ...................................... 15 3.4.1 Studies CN105-078 and CN105-083 ...................................................................... 15 3.4.2 Studies CN105-052 and CN105-053 ...................................................................... 15 3.4.3 Studies 134004 and 134006 .................................................................................... 16 3.4.4 Study 134017 .......................................................................................................... 16 3.4.5 Summary of Uninterpretable Gepirone ER Studies ................................................ 16 3.5 Impact of Dropouts on Demonstration of Efficacy ........................................................ 18 3.6 Meta-Analysis of Gepirone ER Studies ......................................................................... 18 3.6.1 Methodology ........................................................................................................... 19 3.6.2 Results ..................................................................................................................... 20 Fabre-Kramer Pharmaceuticals, Inc. Page iii 10/27/2015 3.6.3 Conclusions from Meta-Analyses ........................................................................... 25 3.7 Additional Efficacy Data ................................................................................................ 26 3.8 Overall Efficacy Summary and Conclusions ................................................................. 27 4. Safety .................................................................................................................................... 28 4.1 Safety Profile .................................................................................................................. 28 4.1.1 Gepirone ER - Overall Safety Assessment ............................................................. 28 4.1.2 Sexual Adverse Events ........................................................................................... 30 5. Risk/Benefit Profile in the Treatment of MDD .................................................................... 32 5.1.1 Additional Clinical Utility of Gepirone ER - Sexual Functioning ......................... 32 5.1.2 Conclusions on Sexual Functioning with Gepirone ER ......................................... 33 5.2 Further Support for Sexual Functioning Benefits .......................................................... 34 5.3 Risk/Benefit Profile ........................................................................................................ 34 6. Discussion and Conclusions ................................................................................................. 36 7. References ............................................................................................................................. 38 8. Appendix 1 – Summaries of 5 Interpretable Studies ............................................................ 42 8.1.1 134001..................................................................................................................... 43 8.1.2 FKGBE007 ............................................................................................................. 48 8.1.3 134002..................................................................................................................... 54 8.1.4 FKGBE008 ............................................................................................................. 60 8.1.5 134023..................................................................................................................... 64 9. Appendix 2 – Summaries of 7 Uninterpretable Studies ........................................................ 68 9.1.1 CN105-078 .............................................................................................................. 69 9.1.2 CN105-083 .............................................................................................................. 75 9.1.3 CN105-052 .............................................................................................................. 81 9.1.4 CN105-053 .............................................................................................................. 85 9.1.5 134004..................................................................................................................... 94 9.1.6 ORG134006 .......................................................................................................... 100 9.1.7 134017................................................................................................................... 106 10. Appendix 3 - Summary of Relapse Prevention Study (28709) ....................................... 113 11. Appendix 4 – Gepirone ER Statistical Review (January 2011) ...................................... 119 Fabre-Kramer Pharmaceuticals, Inc. Page iv 10/27/2015 I. LIST OF TABLES IN TEXT Table 1: Three Recent FDA Approved NCE Antidepressants - Characterization of All Short- Term 3 Arm Comparator Trials ...................................................................................................... 6 Table 2: Gepirone ER – Summary of Short-term Clinical Studies ............................................... 10 Table 3: Summary of Gepirone ER Short-Term Studies – Comparison of Factors Influencing Study Validity ............................................................................................................................... 12 Table 4: Primary Reasons for Characterizing Seven Studies as Uninterpretable ......................... 17 Table 5: Number (%) of Subjects with AEs Regardless of Relationship to Study Drug by Preferred Term and Treatment for AEs Reported by ≥5% of Subjects in any Treatment Group (All Subjects Treated in Gepirone ER Controlled Phase II/III Studies in Depression) ................ 29 Table 6: Incidence of Antidepressant-Related AEs in All Subjects Treated in Gepirone ER Controlled Phase II/III Studies in Depression by Relationship to Study Drug and Treatment .... 30 Table 7: Incidence of Sexual Dysfunction Adverse Events: All Gepirone ER Phase II/III Studies in Depression ................................................................................................................................ 31 Table 8: Flexible Dosing Schedule in Study 134001.................................................................... 43 Table 9: Subjects Discontinued
Load more

Recommended publications
  • Guaiana, G., Barbui, C., Caldwell, DM, Davies, SJC, Furukawa, TA
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Explore Bristol Research Guaiana, G., Barbui, C., Caldwell, D. M., Davies, S. J. C., Furukawa, T. A., Imai, H., ... Cipriani, A. (2017). Antidepressants, benzodiazepines and azapirones for panic disorder in adults: a network meta-analysis. Cochrane Database of Systematic Reviews, 2017(7), [CD012729]. https://doi.org/10.1002/14651858.CD012729 Publisher's PDF, also known as Version of record Link to published version (if available): 10.1002/14651858.CD012729 Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Cochrane Library at https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012729/full . Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms Cochrane Database of Systematic Reviews Antidepressants, benzodiazepines and azapirones for panic disorder in adults: a network meta-analysis (Protocol) Guaiana G, Barbui C, Caldwell DM, Davies SJC, Furukawa TA, Imai H, Koesters M, Tajika A, Bighelli I, Pompoli A, Cipriani A Guaiana G, Barbui C, Caldwell DM, Davies SJC, Furukawa TA, Imai H, Koesters M, Tajika A, Bighelli I, Pompoli A, Cipriani A. Antidepressants, benzodiazepines and azapirones for panic disorder in adults: a network meta-analysis. Cochrane Database of Systematic Reviews 2017, Issue 7.
    [Show full text]
  • Strategies for Managing Sexual Dysfunction Induced by Antidepressant Medication
    King’s Research Portal DOI: 10.1002/14651858.CD003382.pub3 Document Version Publisher's PDF, also known as Version of record Link to publication record in King's Research Portal Citation for published version (APA): Taylor, M. J., Rudkin, L., Bullemor-Day, P., Lubin, J., Chukwujekwu, C., & Hawton, K. (2013). Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews, (5). https://doi.org/10.1002/14651858.CD003382.pub3 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • 52Nd Annual Meeting
    ACNP 52nd Annual Meeting Final Program December 8-12, 2013 The Westin Diplomat Resort & Spa Hollywood, Florida President: David A. Lewis, M.D. Program Committee Chair: Randy D. Blakely, Ph.D. Program Committee Co-Chair: Pat R. Levitt, Ph.D. This meeting is jointly sponsored by the Vanderbilt University School of Medicine Department of Psychiatry and the American College of Neuropsychopharmacology. Dear ACNP Members and Guests, It is a distinct pleasure to welcome you to the 2014 meeting of the American College of Neuropsychopharmacology! This 52nd annual meeting will again provide opportunities for the exercise of the College’s core values: the spirit of Collegiality, promoting in each other the best in science, training and service; participation in Community, pursuing together the goals of understanding the neurobiology of brain diseases and eliminating their burden on individuals and our society; and engaging in Celebration, taking the time to recognize and enjoy the contributions and accomplishments of our members and guests. Under the excellent leadership of Randy Blakely and Pat Levitt, the Program Committee has done a superb job in assembling an outstanding slate of scientific presentations. Based on membership feedback, the meeting schedule has been designed with the goals of achieving an optimal mix of topics and types of sessions, increasing the diversity of participating scientists and creating more time for informal interactions. The presentations will highlight both the breadth of the investigative interests of ACNP membership
    [Show full text]
  • Serotonin and Drug-Induced Therapeutic Responses in Major Depression, Obsessive–Compulsive and Panic Disorders Pierre Blier, M.D., Ph.D
    Serotonin and Drug-Induced Therapeutic Responses in Major Depression, Obsessive–Compulsive and Panic Disorders Pierre Blier, M.D., Ph.D. and Claude de Montigny, M.D., Ph.D. The therapeutic effectiveness of antidepressant drugs in major development of treatment strategies producing greater efficacy depression was discovered by pure serendipity. It took over 20 and more rapid onset of antidepressant action; that, is lithium years before the neurobiological modifications that could addition and pindolol combination, respectively. It is expected mediate the antidepressive response were put into evidence. that the better understanding recently obtained of the Indeed, whereas the immediate biochemical effects of these mechanism of action of certain antidepressant drugs in drugs had been well documented, their antidepressant action obsessive– compulsive and panic disorders will also lead to generally does not become apparent before 2 to 3 weeks of more effective treatment strategies for those disorders. treatment. The different classes of antidepressant [Neuropsychopharmacology 21:91S–98S, 1999] treatments were subsequently shown to enhance serotonin © 1999 American College of Neuropsychopharmacology. neurotransmission albeit via different pre- and postsynaptic Published by Elsevier Science Inc. mechanisms. Clinical trials based on this hypothesis led to the KEY WORDS: Antidepressant; Electroconvulsive shocks; electroconvulsive shock treatment (ECT), which was Lithium; Pindolol; Hippocampus; Orbito-frontal cortex generally given only to hospitalized patients. It took several years after the demonstration of the In the late 1950s, the therapeutic effect of certain drugs antidepressant effect of iproniazide and imipramine to in major depression was discovered by serendipity. An understand that these drugs could interfere with the ca- antidepressant response was observed in patients with tabolism of monoamines.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8.598,119 B2 Mates Et Al
    US008598119B2 (12) United States Patent (10) Patent No.: US 8.598,119 B2 Mates et al. (45) Date of Patent: Dec. 3, 2013 (54) METHODS AND COMPOSITIONS FOR AOIN 43/00 (2006.01) SLEEP DSORDERS AND OTHER AOIN 43/46 (2006.01) DSORDERS AOIN 43/62 (2006.01) AOIN 43/58 (2006.01) (75) Inventors: Sharon Mates, New York, NY (US); AOIN 43/60 (2006.01) Allen Fienberg, New York, NY (US); (52) U.S. Cl. Lawrence Wennogle, New York, NY USPC .......... 514/114: 514/171; 514/217: 514/220; (US) 514/229.5: 514/250 (58) Field of Classification Search (73) Assignee: Intra-Cellular Therapies, Inc. NY (US) None See application file for complete search history. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (56) References Cited U.S.C. 154(b) by 215 days. U.S. PATENT DOCUMENTS (21) Appl. No.: 12/994,560 6,552,017 B1 4/2003 Robichaud et al. 2007/0203120 A1 8, 2007 McDevitt et al. (22) PCT Filed: May 27, 2009 FOREIGN PATENT DOCUMENTS (86). PCT No.: PCT/US2O09/OO3261 S371 (c)(1), WO WOOOf77OO2 * 6, 2000 (2), (4) Date: Nov. 24, 2010 OTHER PUBLICATIONS (87) PCT Pub. No.: WO2009/145900 Rye (Sleep Disorders and Parkinson's Disease, 2000, accessed online http://www.waparkinsons.org/edu research/articles/Sleep PCT Pub. Date: Dec. 3, 2009 Disorders.html), 2 pages.* Alvir et al. Clozapine-Induced Agranulocytosis. The New England (65) Prior Publication Data Journal of Medicine, 1993, vol. 329, No. 3, pp. 162-167.* US 2011/0071080 A1 Mar.
    [Show full text]
  • Comparative Efficacy and Acceptability of Pharmacological Treatments in the Acute Phase Treatment of Bipolar Depression: a Multi
    COMPARATIVE EFFICACY AND ACCEPTABILITY OF PHARMACOLOGICAL TREATMENTS IN THE ACUTE PHASE TREATMENT OF BIPOLAR DEPRESSION: A MULTIPLE TREATMENT META-ANALYSIS [PROTOCOL] Tomofumi Miura, Toshi A. Furukawa, Hisashi Noma, Shiro Tanaka, Keisuke Motomura, Hiroshi Mitsuyasu, Satomi Katsuki, Andrea Cipriani, Sarah Stockton, John Geddes, Georgia Salanti, Shigenobu Kanba Background Description of the condition In late 19th century, Emil Kraepelin classified the major endogenous psychoses into two psychotic illnesses, manic-depressive illness and dementia praecox (Kraepelin’s dichotomy) (Trede et al. , 2005). His concept of manic-depressive illness had covered all of the major clinical forms of severe, moderate and mild melancholia. In 1957, Leonhard proposed to distinguish Kraepelin’s manic-depressive illness into bipolar illness, in which patients had histories of both depression and mania, and monopolar illness, in which patients only had histories of depression (Leonhard, 1979). This basic idea of the bipolar-unipolar distinction was supported by Angst and by Perris in 1966 (Angst, 1966, Perris, 1966), and it continues in the recent diagnostic classification system of mood disorders in DSM-IV(American Psychiatric Association, 1994) and ICD-10 (WHO, 1993). Bipolar disorder is a complex disorder, which is characterized by recurrent episodes of depression and mania (bipolar I disorder) or hypomania (bipolar II disorder)(American Psychiatric Association, 1994). The lifetime prevalence of any bipolar disorders, bipolar I and II disorders have been estimated at 1.1%, 0.7% and 0.5% respectively using the World Mental Health Survey version of the WHO Composite International Diagnostic Interview (Suppes et al. , 2001). The mean age at onset of bipolar disorder is reported to be in the early 20s, but its complex clinical features make its diagnosis difficult and there is a difference of about 8 years between age at onset and age at first treatment (Suppes, Leverich, 2001).
    [Show full text]
  • Conformational Flexibility of Buspirone Analogues from X-Ray in the Solids and Nmr in Solution
    CONFORMATIONAL FLEXIBILITY OF BUSPIRONE ANALOGUES FROM X-RAY IN THE SOLIDS AND NMR IN SOLUTION Anna Bielenica 1, Andrzej Zimniak 2, Izabela Dyba áa3, Anna E. Kozio á3, Marta Struga 1 1 Department of Medical Chemistry, Medical University of Warsaw, Warsaw, Poland 2 Department of Physical Chemistry, Medical University of Warsaw, Warsaw, Poland 3 Faculty of Chemistry, Maria Curie-Sk áodowska University, Lublin, Poland Bioactive molecular conformation of a drug is one of the key points for understanding the ligand-receptor interactions. N-substituted arylpiperazines are important class of 5-HT receptor ligands (particularly 5-HT 1A , 5-HT 2A and 5-HT 7) widely used in the treatment of anxiety, depression, schizophrenia, sleep and memory disorders. Majority of compounds of this group possess hydrocarbon linker of different length and type, which connects the arylpiperazine moiety with the second terminal group, e. g. cyclic imide. According to SAR (structure-activity relationship) analyses, the presence of an aryl group at N4 atom of the piperazine ring is critical in respect to the biological activity of these compounds. The protonated nitrogen atom forms the hydrogen bond with the carboxyl oxygen of the Asp 3.32 side chain, that is crucial for the interaction with the 5-HT receptors. In addition, the aromatic ring stabilizes the ligand binding by a CH…ʌ interaction with the Phe 6.52 residue. Nowak et al. claimed that o-methoxy-phenyl moieties of a ligand form a hydrogen bond with the hydroxyl group of Ser 5.42 [1]. Some authors have underlined also a role of the terminal hydrophobic imide part in a stabilization of the ligand-receptor complex by ʌ…ʌ and/or dipole…dipole interactions [2].
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]
  • Hallucinogens: an Update
    National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Hallucinogens: An Update 146 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Hallucinogens: An Update Editors: Geraline C. Lin, Ph.D. National Institute on Drug Abuse Richard A. Glennon, Ph.D. Virginia Commonwealth University NIDA Research Monograph 146 1994 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGEMENT This monograph is based on the papers from a technical review on “Hallucinogens: An Update” held on July 13-14, 1992. The review meeting was sponsored by the 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 material 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. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company.
    [Show full text]
  • Phd Thesis Project: Pharmacological and Toxicological Investigations of New Psychoactive Substances, Supervised by Prof
    PHARMACOLOGICAL AND TOXICOLOGICAL INVESTIGATIONS OF NEW PSYCHOACTIVE SUBSTANCES Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Dino Lüthi aus Rüderswil, Bern Basel, 2018 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung-Nicht kommerziell 4.0 International Lizenz (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.de). Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von Prof. Stephan Krähenbühl, Prof. Matthias E. Liechti und Prof. Anne Eckert. Basel, den 26.06.2018 Prof. Martin Spiess Dekan der Philosophisch- Naturwissenschaftlichen Fakultät PHARMACOLOGICAL AND TOXICOLOGICAL INVESTIGATIONS OF NEW PSYCHOACTIVE SUBSTANCES “An adult must make his own decision as to whether or not he should expose himself to a specific drug, be it available by prescription or proscribed by law, by measuring the potential good and bad with his own personal yardstick.” ― Alexander Shulgin, Pihkal: A Chemical Love Story. PREFACE This thesis is split into a pharmacology part and a toxicology part. The pharmacology part consists of investigations on the monoamine transporter and receptor interactions of traditional and newly emerged drugs, mainly stimulants and psychedelics; the toxicology part consists of investigations on mechanisms of hepatocellular toxicity of synthetic cathinones. All research described in this thesis has been published in peer-reviewed journals, and was performed between October 2014 and June 2018 in the Division of Clinical Pharmacology and Toxicology at the Department of Biomedicine of the University Hospital Basel and University of Basel, and partly at the pRED Roche Innovation Center Basel at F.
    [Show full text]
  • Eptapirone | Medchemexpress
    Inhibitors Product Data Sheet Eptapirone • Agonists Cat. No.: HY-19946 CAS No.: 179756-58-2 Molecular Formula: C₁₆H₂₃N₇O₂ • Molecular Weight: 345.4 Screening Libraries Target: 5-HT Receptor Pathway: GPCR/G Protein; 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 : 50 mg/mL (144.76 mM; Need ultrasonic) Mass Solvent 1 mg 5 mg 10 mg Concentration Preparing 1 mM 2.8952 mL 14.4760 mL 28.9519 mL Stock Solutions 5 mM 0.5790 mL 2.8952 mL 5.7904 mL 10 mM 0.2895 mL 1.4476 mL 2.8952 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 (7.24 mM); Clear solution 2. Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (7.24 mM); Clear solution 3. Add each solvent one by one: 10% DMSO >> 90% corn oil Solubility: ≥ 2.5 mg/mL (7.24 mM); Clear solution BIOLOGICAL ACTIVITY Description Eptapirone (F11440) is a potent, selective, high efficacy 5-HT1A receptor agonist with marked anxiolytic and antidepressant potential. IC₅₀ & Target 5-HT1A Receptor In Vitro The affinity of Eptapirone (F11440) for 5-HT1Abinding sites (pKi, 8.33) was higher than that of buspirone (pKi , 7.50), and somewhat lower than that of flesinoxan (pKi , 8.91).In vivo, Eptapirone (F11440) was 4- to 20-fold more potent than Page 1 of 2 www.MedChemExpress.com flesinoxan, and 30- to 60-fold more potent than buspirone, in exerting 5-HT1A agonist activity at pre- and postsynaptic receptors in rats (measured by, for example, its ability to decrease hippocampal extracellular serotonin (5-HT) levels and to increase plasma corticosterone levels, respectively).
    [Show full text]
  • WO 2011/064769 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date t 3 June 2011 (03.06.2011) WO 201 1/064769 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/00 (2006.01) A61K 31/506 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 9/70 (2006.01) A61P 5/24 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/IL20 10/000976 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 22 November 2010 (22.1 1.2010) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/264,025 24 November 2009 (24.1 1.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, (71) Applicant (for all designated States except US): YIS- ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, SUM RESEARCH DEVELOPMENT COMPANY OF TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, THE HEBREW UNIVERSITY OF JERUSALEM EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, LTD.
    [Show full text]