WO2000027374A3 - The use of excitatory amino acid transporter inhibitors to reduce cns white matter injury - Google Patents

The use of excitatory amino acid transporter inhibitors to reduce cns white matter injury Download PDF

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Publication number
WO2000027374A3
WO2000027374A3 PCT/CA1999/001037 CA9901037W WO0027374A3 WO 2000027374 A3 WO2000027374 A3 WO 2000027374A3 CA 9901037 W CA9901037 W CA 9901037W WO 0027374 A3 WO0027374 A3 WO 0027374A3
Authority
WO
WIPO (PCT)
Prior art keywords
amino acid
white matter
excitatory amino
acid transporter
transporter inhibitors
Prior art date
Application number
PCT/CA1999/001037
Other languages
French (fr)
Other versions
WO2000027374A2 (en
WO2000027374B1 (en
Inventor
Peter Stys
Original Assignee
Peter Stys
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Peter Stys filed Critical Peter Stys
Priority to AU11428/00A priority Critical patent/AU1142800A/en
Publication of WO2000027374A2 publication Critical patent/WO2000027374A2/en
Publication of WO2000027374A3 publication Critical patent/WO2000027374A3/en
Publication of WO2000027374B1 publication Critical patent/WO2000027374B1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401—Proline; Derivatives thereof, e.g. captopril
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

This invention provides a method of reducing the damaging effect of CNS white matter injury (including traumatic CNS injury, anoxia, and ischemia) to mammalian CNS tissue, particularly spinal cord tissue, by in vivo treatment thereof with inhibitors of excitatory amino acid transporters, such as the Na+-dependent glutamate transporter and pharmaceutical compositions comprising said inhibitors.
PCT/CA1999/001037 1998-11-06 1999-11-08 The use of excitatory amino acid transporter inhibitors to reduce cns white matter injury WO2000027374A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU11428/00A AU1142800A (en) 1998-11-06 1999-11-08 The use of excitatory amino acid transporter inhibitors to reduce cns white matter injury

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CA2252996 1998-11-06
CA2,252,996 1998-11-06
CA2,282,236 1999-09-16
CA002282236A CA2282236A1 (en) 1998-11-06 1999-09-16 The use of excitatory amino acid transporter inhibitors to protect against cns white matter injury

Publications (3)

Publication Number Publication Date
WO2000027374A2 WO2000027374A2 (en) 2000-05-18
WO2000027374A3 true WO2000027374A3 (en) 2000-12-21
WO2000027374B1 WO2000027374B1 (en) 2001-06-21

Family

ID=25680622

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA1999/001037 WO2000027374A2 (en) 1998-11-06 1999-11-08 The use of excitatory amino acid transporter inhibitors to reduce cns white matter injury

Country Status (3)

Country Link
AU (1) AU1142800A (en)
CA (1) CA2282236A1 (en)
WO (1) WO2000027374A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1365758A2 (en) * 2000-10-30 2003-12-03 Annovis, Inc. Method for modulation, stimulation, and inhibition of glutamate reuptake
CN109111391A (en) * 2018-07-03 2019-01-01 杭州师范大学 The chiral pyrrolidine derivative and its synthetic method of a kind of ring skeleton containing ternary and application
KR20210072770A (en) * 2018-10-02 2021-06-17 조지타운 유니버시티 Compositions and methods for treating inflammatory nervous system disorders

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991006536A1 (en) * 1989-10-25 1991-05-16 The Regents Of The University Of California Method of inhibiting the transport of l-glutamate
WO1997040871A1 (en) * 1996-04-30 1997-11-06 Medtronic, Inc. Method of treating movement disorders by brain infusion

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991006536A1 (en) * 1989-10-25 1991-05-16 The Regents Of The University Of California Method of inhibiting the transport of l-glutamate
WO1997040871A1 (en) * 1996-04-30 1997-11-06 Medtronic, Inc. Method of treating movement disorders by brain infusion

Non-Patent Citations (16)

* Cited by examiner, † Cited by third party
Title
BRIDGES R J ET AL: "A CONFORMATIONALLY CONSTRAINED COMPETITIVE INHIBITOR OF THE SODIUM-DEPENDENT GLUTAMATE TRANSPORTER IN FOREBRAIN SYNAPTOSOMES: L-ANTI-ENDO-3,4-METHANOPYRROLIDINE DICARBOXYLATE", NEUROSCIENCE LETTERS,IE,LIMERICK, vol. 174, no. 2, 1994, pages 193 - 197, XP000910903, ISSN: 0304-3940 *
BRIDGES R J ET AL: "A PHARMACOLOGICAL REVIEW OF COMPETITIVE INHIBITORS AND SUBSTRATES OF HIGH-AFFINITY, SODIUM-DEPENDENT GLUTAMATE TRANSPORT IN THE CENTRAL NERVOUS SYSTEM", CURRENT PHARMACEUTICAL DESIGN,NL,BENTHAM SCIENCE PUBLISHERS, SCHIPHOL, vol. 5, no. 5, May 1999 (1999-05-01), pages 363 - 379, XP000910814, ISSN: 1381-6128 *
CHIU S Y ET AL: "NEUROTRANSMITTER-MEDIATED SIGNALING BETWEEN AXONS AND GLIAL CELLS", GLIA,US,WILEY-LISS, NEW YORK, NY, vol. 11, no. 2, June 1994 (1994-06-01), pages 191 - 200, XP000910854, ISSN: 0994-1491 *
DATABASE BIOTECHNO. ABSTR. XP002144545 *
ESSLINGER C S ET AL: "Structural determinants of substrates and inhibitors: probing glutamate transporters with 2,4-methanopyrrolidine-2,4-dicarboxylate", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,GB,OXFORD, vol. 8, no. 21, 3 November 1998 (1998-11-03), pages 3101 - 3106, XP004141883, ISSN: 0960-894X *
HIRATA A ET AL: "AMPA RECEPTOR-MEDIATED SLOW NEURONAL DEATH IN THE RAT SPINAL CORD INDUCED BY LONG-TERM BLOCKADE OF GLUTAMATE TRANSPORTERS WITH THA", BRAIN RESEARCH,NL,AMSTERDAM, vol. 771, no. 1, 1997, pages 37 - 44, XP000910852, ISSN: 0006-8993 *
KAWAKAMI H. ET AL: "Glutamate transporter and neuronal cell death", CLINICAL NEUROLOGY, (1996), 36/12 (1316-1317), 6 REFERENCE(S) CODEN: RISHDJ ISSN: 0009-918X, Dr. H. Kawakami, Third Dept. of Internal Medicine, Hiroshima University, Hiroshima, Japan., XP000910824 *
LEBRUN B ET AL: "NEW BETA-HYDROXYASPARTATE DERIVATIVES ARE COMPETITIVE BLOCKERS FOR EXCITATORY AMINO ACID TRANSPORTERS", SOCIETY FOR NEUROSCIENCE ABSTRACTS,US,SOCIETY FOR NEUROSCIENCE, vol. 23, no. 1/02, 1997, pages ABS45010, XP000910902, ISSN: 0190-5295 *
LUCAS J H (REPRINT) ET AL: "Physical injury of neurons: Important roles for sodium and chloride ions", NEUROSCIENTIST, (MAR 1997) VOL. 3, NO. 2, PP. 89-101. PUBLISHER: WILLIAMS & WILKINS, 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436. ISSN: 1073-8584., OHIO STATE UNIV, DEPT PHYSIOL, COLUMBUS, OH 43210;IOWA STATE UNIV, AMES, IA 50011, XP000910898 *
LYSKO P G (REPRINT) ET AL: "NEUROPROTECTIVE EFFECTS OF TETRODOTOXIN AS A NA+ CHANNEL MODULATOR AND GLUTAMATE RELEASE INHIBITOR IN CULTURED RAT CEREBELLAR NEURONS AND IN GERBIL GLOBAL BRAIN ISCHEMIA", STROKE, (DEC 1994) VOL. 25, NO. 12, PP. 2476-2482. ISSN: 0039-2499., SMITHKLINE BEECHAM PHARMACEUT, DEPT CARDIOVASC PHARMACOL, POB 1539, UW2510, KING OF PRUSSIA, PA, 19406 (Reprint), XP000910774 *
MADL J E ET AL: "Adenosine triphosphate depletion reverses sodium-dependent, neuronal uptake of glutamate in rat hippocampal slices.", JOURNAL OF NEUROSCIENCE, (1993 OCT) 13 (10) 4429-44., XP000910738 *
ROTHSTEIN J D ET AL: "NEUROPROTECTIVE STRATEGIES IN A MODEL OF CHRONIC GLUTAMATE-MEDIATEDMOTOR NEURON TOXICITY", JOURNAL OF NEUROCHEMISTRY,US,NEW YORK, NY, vol. 65, no. 2, 1995, pages 643 - 651, XP000910839, ISSN: 0022-3042 *
SHIMAMOTO K ET AL: "DL-THREO-SS-BENZYLOXYASPARTATE, A POTENT BLOCKER OF EXCITATORY AMINO ACID TRANSPORTERS", MOLECULAR PHARMACOLOGY,US,BALTIMORE, MD, vol. 53, no. 2, February 1998 (1998-02-01), pages 195 - 201, XP000910909, ISSN: 0026-895X *
SPRINGER J E ET AL: "4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake.", JOURNAL OF NEUROCHEMISTRY, (1997 JUN) 68 (6) 2469-76., XP000910739 *
STYS P K: "Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics.", JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, (1998 JAN) 18 (1) 2-25. REF: 184, XP000910746 *
YAN ET AL.: "Role of glutamate transporter in the pathogenesis of cerebral ischemia in rats", CHINESE JOURNAL OF NEUROLOGY, vol. 31, no. 2, 1998, pages 106 - 108 *

Also Published As

Publication number Publication date
WO2000027374A2 (en) 2000-05-18
CA2282236A1 (en) 2000-05-06
WO2000027374B1 (en) 2001-06-21
AU1142800A (en) 2000-05-29

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