CA2450801A1 - Drugs that enhance synaptic responses mediated by ampa receptors - Google Patents

Drugs that enhance synaptic responses mediated by ampa receptors Download PDF

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CA2450801A1
CA2450801A1 CA002450801A CA2450801A CA2450801A1 CA 2450801 A1 CA2450801 A1 CA 2450801A1 CA 002450801 A CA002450801 A CA 002450801A CA 2450801 A CA2450801 A CA 2450801A CA 2450801 A1 CA2450801 A1 CA 2450801A1
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CA2450801C (en
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Gary S. Lynch
Gary A. Rogers
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University of California
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Gary S. Lynch
Gary A. Rogers
The Regents Of The University Of California
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    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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Abstract

This invention discloses compounds having the structure (see formula I) that are useful for enhancing synaptic responses mediated by AMPA receptors, methods for the preparation thereof, and methods for their use for treatment of subjects suffering from impaired nervous or intellectual functioning due to deficiencies in the number of excitatory synapses or in the number of AMPA receptors. The invention compounds can also be used for the treatment of non-impaired subjects for enhancing performance in sensory-motor and cognitive tasks which depend on brain networks utilizing AMPA receptors and for improving memory encoding.

Claims (19)

1. A compound having the structure:

wherein:
-Y- is selected from:
, wherein y is 3, 4, or 5; or ; when -J- is selected from:

; or -(CR2)x-, wherein x is 4, 5, or 6, -C x R(2x-2)-, when -J- is:

-R is hydrogen or a straight chain or branched chain alkyl group having 1-6 carbon atoms;
each -M- is independently selected from:
-C(H)-, or -C(Z)-, wherein Z is selected from:
-R, or -OR;
wherein M can optionally be linked to Y by a linking moiety selected from -C n' H2n'-, -C n H(2n'-1)-, -O- or -NR-, wherein n' is 0 or 1;
each -Y'- is independently selected from:

-O-, -NR- or -N=; and -Z'- is selected from:
-(CR2)z-, wherein z is 1, 2, or 3, or -C z' R(2z'-1)-, wherein z' is 1 or 2, when one -Y'- is -N=, or -C2R2- when both -Y'- are -N= or both -Y'-are -O-;
with the proviso that when each M is -C(H)-, each Y' is -O-, and Z' is -CH2-, then Y is not -(CH2)4,5-;
or wherein:

-Y-, and -M- are as defined above, or wherein:

-Y-, and -M- are as defined above.
2. A compound according to claim 1 wherein -Y-is ~
, and y is selected from 3 or 4.
3. A compound according to claim 2 wherein each Y' is -O-, and Z' is -CH2-.
4. A compound according to claim 1 wherein Y
is -(CR(2x-2))x-, and x is selected from 4 or 5.
5. A compound according to claim 1 wherein Z' is selected from -CR2-, -CR2-CH2-, -CR=, or -CR=CH-, wherein each R is independently H or a straight chain or branched chain alkyl group having 1-6 carbon atoms.
6. A compound according to claim 2 wherein -OR
is -OCH3.
7. A compound according to claim 4 wherein -NR2 is -N(CH3)2.
8. A compound according to claim 1 having the structure:

wherein:

Y' is O, N or NR', Y'' is optional, and when present, is O, N or NR', R' is H or a straight chain or branched chain alkyl group having 1-4 carbon atoms, a = 3, 4, 5 or 6, b = an even number between 6-12, inclusive, depending on the value of a, c = 1 or 2, d = 0, 1 or 3, or the combination of Y' and C c H d -R' produces a dialkylamino derivative thereof, wherein a dialkylamino group replaces the heterocyclic ring fused to the core aromatic ring.
9. A method for producing the compound of claim 1 comprising:
(a) contacting a benzoic acid derivative under conditions suitable to activate the carboxy group thereof for the formation of an amide therefrom, wherein said benzoic acid derivative has the structure:

wherein -M-, -Y'-, and Z' are as defined above; or wherein -M- and -R are as defined above; or wherein -M- and -R are as defined above; and (b) contacting the activated benzoic acid derivative produced in step (a) with a nitrogen-containing heterocyclic compound of the structure:

wherein Y is as defined above, wherein said contacting is carried out under conditions suitable to produce the desired imides or amides.
10. A method according to claim 9 wherein the carboxy group of said benzoic acid derivative is activated for the formation of an amide therefrom by contacting with carbonyl diimidazole.
11. A method for producing the compound of claim 1 comprising:
(a) contacting a benzoic acid derivative with at least two equivalents of a suitable bass in suitable solvent, then contacting the resulting ionized benzoic acid derivative with pivaloyl chloride or a reactive carboxylic acid anhydride under conditions suitable to produce a mixed anhydride containing said benzoic acid, wherein said benzoic acid derivative has the structure:

wherein -M-, -Y'-, and Z' are as defined above or wherein -M- and -R are as defined above; or wherein -M- and -R are as defined above; and (b) contacting said mixed anhydride produced in step (a) with a nitrogen-containing heterocyclic compound of the structure:

wherein Y is as defined above, wherein said contacting is carried out under conditions suitable to produce the desired imides or amides.
12. A method for producing the compound of claim 1 comprising:
(a) contacting 3,4-(methylenedihetero)-benzaldehyde with ammonia under conditions suitable to form an imine derivative thereof, (b) contacting the imine produced in step (a) with:

under conditions suitable to form a benzyloxy carbonyl imine, (c) contacting the product of step (b) with a simple conjugated diene under cycloaddition reaction conditions; and (d) contacting the reaction product of step (c) with a Lewis acid under conditions suitable for Friedel-Crafts acylation to occur.
13. A method according to claim 12, further comprising separating the enantiomers produced in the Friedel-Crafts reaction.
14. A method for producing the compound of claim 1 comprising:
(a) contacting 2,3-dihydroxy naphthalene with 1,2-dibromoethane in the presence of base under conditions suitable to produce an ethylenedioxy derivative of naphthalene, (b) contacting the ethylenedioxy derivative of naphthalene produced in step (a) with a suitable oxidizing agent under conditions suitable to produce 4,5-ethylenedioxyphthaldehydic acid, (c) contacting the product of step (b) with anhydrous ammonia under conditions suitable to form an imine, which is then treated with a suitable carbonyl-activating agent under cyclization conditions suitable to form an acyl imine, and (d) contacting the product of step (c) with a simple conjugated diene under conditions suitable for cycloaddition to occur.
15. A formulation useful for enhancing synaptic responses mediated by AMPA receptors, said formulation comprising:
a compound according to claim 1, and a pharmaceutically acceptable carrier.
16. A method for the treatment of a subject to enhance synaptic response mediated by AMPA receptors, said method comprising administering to said subject an effective amount of a compound having the structure:

wherein:

-Y- is selected from:
, wherein y is 3, 4, or 5; or ; when -J- is selected from:
; or -(CR2)x-, wherein x is 4, 5, or 6, -C x R(2x-2)-, when -J- is:
;
-R is hydrogen or a straight chain or branched chain alkyl group having 1-6 carbon atoms;
each -M- is independently selected from:
-C(H)-, or -C(Z)-, wherein Z is selected from:
-R, or -OR;
wherein M can optionally be linked to Y by a linking moiety selected from -C n' H2n'-, -C n H(2n'-1)-, -O- or -NR-, wherein n' is 0 or 1;
each -Y'- is independently selected from:
-O-, -NR- or -N=; and -Z'- is selected from:
-(CR2)z-, wherein z is 1, 2, or 3, or -C z,R(2z'-1)-, wherein z' is 1 or 2, when one -Y' - is -N=, or -C2R2- when both -Y' are -N= or both -Y'-are -O-; or wherein:
-Y-, and -M- are as defined above, or wherein:
-Y-, and -M- are as defined above.
17. A method according to claim 16 wherein the performance of said subject is improved on sensory-motor problems or cognitive tasks dependent upon brain networks utilizing AMPA receptors, wherein the strength of memory encoding by said subject is improved, or wherein brain functioning is improved in subjects with deficiencies in the number of excitatory synapses or in the number of AMPA receptors.
18. A method for decreasing the amount of time needed for a subject to learn a cognitive, motor or perceptual task, or for increasing the time for which said subject retains cognitive, motor or perceptual tasks, or for decreasing the quantity and/or severity of errors made by a subject in recalling a cognitive, motor or perceptual task, said method comprising administering to said subject an effective amount of a compound having the structure:

wherein:
-Y- is selected from:

wherein y is 3, 4, or 5; or when -J- is selected from:
or -(CR z)x-, wherein x is 4, 5, or 6, C x R(2x-2)- when -J- is:

-R is hydrogen or a straight chain or branched chain alkyl group having 1-6 carbon atoms;

each -M- is independently selected from:
-C(H)-, or -C(Z)-, wherein Z is selected from:
-R, or -OR;
wherein M can optionally be linked to Y by a linking moiety selected from -C n'H2n'-, C n H(2n'-1)-, -O- or -NR-, wherein n' is 0 or 1;
each -Y'- is independently selected from:
-O-, -NR- or -N=; and -Z'- is selected from:
-(CR2)z-, wherein z is 1, 2, or 3, or -C z'R(2z'-1)-, wherein z' is 1 or 2, when one -Y'- is -N=, or -C2R2- when both -Y'- are -N= or both -Y'-are -O-; or wherein:
-Y-, and -M- are as defined above, or wherein:
I
-Y-, and -M- are as defined above.
19. Compounds of the formula:

wherein:
-Y- is selected from:

wherein y is 3, 4, or 5; or when -J- is selected from:

or -(CR2)x-, wherein x is 4, 5, or 6, -C x R(2x-2)-, when -J- is -R is hydrogen or a straight chain or branched chain alkyl group having 1-6 carbon atoms;
each -M- is independently selected from:
-C(H)-, or -C(Z)-, wherein Z is selected from:
-R, or -OR;
wherein M can optionally be linked to Y by a linking moiety selected from --C n'H2n'-, -C n H(2n'-1)-, -O- or -NR-, wherein n' is 0 or 1;
each -Y'- is independently selected from:
-O--NR- or -N=; and -Z'- is selected from:
-(CR2)z-, wherein z is 1, 2, or 3, or -Cz'R(2z'-1)-, wherein z' is 1 .or 2, when one -Y'- is -N=, or -C2R2- when both -Y'- are -N= or both -Y'-are -O-;
with the proviso that when each M is -C(H)-, each Y' is -O-, and Z' is -CH2-, then Y is not -(CH2)4,5-;
or wherein:
-Y-, and -M- are as defined above, or wherein:
-Y-, and -M- are as defined above for use in the manufacture of a medicament for decreasing the amount of time needed for a subject to learn a cognitive, motor or perceptual task, or for increasing the time for which said subject retains cognitive, motor or perceptual tasks, or for decreasing the quantity and/or severity of errors made by a subject in recalling a cognitive, motor or perceptual task.
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Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1156043T3 (en) 1992-07-24 2004-03-01 Univ California Drugs that enhance synaptic responses mediated by ampa receptors
US6274600B1 (en) * 1995-06-05 2001-08-14 The Regents Of The University Of California Heteroatom substituted benzoyl derivatives that enhance synaptic responses mediated by AMPA receptors
US5650409A (en) * 1995-06-02 1997-07-22 Cortex Pharmaceuticals, Inc. Benzoyl piperidines/pyrrolidines for enhancing synaptic response
US5773434A (en) * 1995-08-30 1998-06-30 Gary A. Rogers Facilitation of AMPA receptor-mediated synaptic transmission in brain as a treatment for schizophrenia
ATE478672T1 (en) * 1996-01-29 2010-09-15 Univ California METHOD OF TREATING SEXUAL MALFUNCTIONS
US5736543A (en) * 1996-04-03 1998-04-07 The Regents Of The University Of California Benzoxazines for enhancing synaptic response
CA2250856A1 (en) * 1996-04-19 1997-10-30 The Regents Of The University Of California Treatment of mood/affective disorders by glutamatergic upmodulators
AU4416197A (en) * 1996-09-17 1998-04-14 Regents Of The University Of California, The Positive ampa receptor modulation to enhance brain neurotrophic factor expression
US6110935A (en) * 1997-02-13 2000-08-29 The Regents Of The University Of California Benzofurazan compounds for enhancing glutamatergic synaptic responses
US5985871A (en) * 1997-12-24 1999-11-16 Cortex Pharmaceuticals, Inc. Benzoxazine compounds for enhancing synaptic response
US6124278A (en) * 1998-04-03 2000-09-26 The Regents Of The University Of California Acylbenzoxazines for enhancing synaptic response
PE20000942A1 (en) * 1998-07-31 2000-09-28 Lilly Co Eli DERIVATIVES OF AMIDE, CARBAMATE AND UREA
US6011991A (en) * 1998-12-07 2000-01-04 Technology Patents, Llc Communication system and method including brain wave analysis and/or use of brain activity
TWI232863B (en) 2001-06-11 2005-05-21 Akzo Nobel Nv Benzoxazepine derivatives
SK287583B6 (en) 2001-06-14 2011-03-04 N.V. Organon (Pyrido/thieno)-[f]-oxazepin-5one derivatives, pharmaceutical composition containing thereof and their use
US6562972B1 (en) * 2001-07-19 2003-05-13 Air Products And Chemicals, Inc. Method for preparing heterocyclic-carboxylic acids
SK2292004A3 (en) 2001-11-26 2004-09-08 Cortex Pharma Inc Carbonyl benzoxazine compounds for enhancement of glutamatergic synaptic responses
WO2004062616A2 (en) 2003-01-13 2004-07-29 Cortex Pharmaceuticals, Inc. Method of treating cognitive decline due to sleep deprivation and stress
EP1715863B1 (en) * 2004-01-26 2012-05-09 Cortex Pharmaceuticals, Inc. Enhancement of ampakine-induced facilitation of synaptic responses by cholinesterase inhibitors
US20060063707A1 (en) * 2004-09-17 2006-03-23 Lifelike Biomatic, Inc. Compositions for enhancing memory and methods therefor
TW200800959A (en) 2005-06-10 2008-01-01 Wyeth Corp Piperazine-piperidine antagonists and agonists of the 5-HT1a receptor
WO2007060144A2 (en) 2005-11-22 2007-05-31 Neurosearch A/S Novel quinoxaline derivatives and their medical use
WO2008027648A2 (en) * 2006-06-26 2008-03-06 Case Western Reserve University Methods and compositions for treating pathologies associated with bdnf signaling
WO2008025148A1 (en) 2006-08-31 2008-03-06 The Governors Of The University Of Alberta Method of inhibition of respiratory depression using positive allosteric ampa receptor modulators
US20100234349A1 (en) 2006-09-04 2010-09-16 Olsen Gunnar M Pharmaceutical combinations of a nicotine receptor modulator and a cognitive enhancer
WO2008060375A2 (en) * 2006-10-06 2008-05-22 The Regents Of The University Of Californina Upregulating bdnf levels to mitigate mental retardation
CA2674321A1 (en) * 2007-01-03 2008-07-17 Cortex Pharmaceuticals, Inc. 3-substituted-[1,2,3]benzotriazinone compounds for enhancing glutamatergic synaptic responses
RS52108B (en) 2007-01-03 2012-08-31 Les Laboratoires Servier 3-substituted-[1,2,3]-benzotriazinone compound for enhancing glutamatergic synaptic responses
CL2008000119A1 (en) 2007-01-16 2008-05-16 Wyeth Corp COMPOUNDS DERIVED FROM PIRAZOL, ANTAGONISTS OF THE NICOTINIC ACETILCOLINE RECEIVER; PHARMACEUTICAL COMPOSITION; AND USE IN THE TREATMENT OF DISEASES SUCH AS SENILE DEMENTIA, ALZHEIMER AND SCHIZOPHRENIA.
AU2008254960B2 (en) 2007-05-17 2014-11-27 Cortex Pharmaceuticals, Inc. Di-substituted amides for enhancing glutamatergic synaptic responses
MX2010001631A (en) * 2007-08-10 2010-03-15 Cortex Pharma Inc Bicyclic amides for enhancing glutamatergic synaptic responses.
US8168632B2 (en) 2007-08-10 2012-05-01 Cortex Pharmaceuticals, Inc. Bicyclic amide derivatives for the treatment of respiratory disorders
US8071914B2 (en) 2007-12-26 2011-12-06 Noboru Oshima Heating apparatus
WO2010054336A2 (en) * 2008-11-10 2010-05-14 The Regents Of The University Of California Therapeutic uses of ampa receptor modulators for treatment of motor dysfunction
EA018994B1 (en) * 2009-02-02 2013-12-30 Кортекс Фармасеутикалс, Инк. Bicyclic amide derivatives for enhancing glutamatergic synaptic responses
PT105083A (en) 2009-04-28 2011-07-25 Univ De Coimbra The use of ampakines and other modulators of ionotropic glutamate receptors in the production of new neurons derived from neural stem cells.
EP2544688B1 (en) 2010-03-02 2016-09-07 President and Fellows of Harvard College Methods and compositions for treatment of angelman syndrome
AU2012225784B2 (en) 2011-03-04 2016-03-17 The Regents Of The University Of California Locally released growth factors to mediate motor recovery after stroke
EP3485882A1 (en) 2013-01-25 2019-05-22 Case Western Reserve University Compositions for the treatment of pervasive development disorders
BR112015031249A2 (en) 2013-06-13 2017-07-25 Veroscience Llc treatment method, method for treating a metabolic disorder or a key element thereof, method for normalizing a daily dopamine release rate in the sumn, method for stimulating dopamine release from dopaminergic neurons in an individual's sumn and pharmaceutical composition
CN107286114B (en) 2016-04-13 2020-08-18 中国人民解放军军事医学科学院毒物药物研究所 Brain-targeted prodrug of AMPA receptor synergist and medical application thereof
EP3684463A4 (en) 2017-09-19 2021-06-23 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
US11318277B2 (en) 2017-12-31 2022-05-03 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
WO2020056418A1 (en) 2018-09-14 2020-03-19 Neuroenhancement Lab, LLC System and method of improving sleep
US11786694B2 (en) 2019-05-24 2023-10-17 NeuroLight, Inc. Device, method, and app for facilitating sleep

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2456991A (en) * 1946-01-16 1948-12-21 Thompson Boyce Plant Res 3, 4-methylenedioxyphenyl-propylene compound
US2487179A (en) * 1946-08-23 1949-11-08 Thompson Boyce Plant Res Organic compounds
US2773062A (en) * 1953-10-06 1956-12-04 Thompson Boyce Plant Res Organic compounds and insecticidal compositions
FR1534547A (en) * 1966-08-23 1968-07-26 May & Baker Ltd New quaternary ammonium salts of semicarbazones and thiosemicarbazones and their preparation
US3869431A (en) * 1973-03-12 1975-03-04 Firestone Tire & Rubber Co Polyamides and their production
US3981864A (en) * 1973-09-08 1976-09-21 Eisai Co., Ltd. 1,3-Benzodioxol derivatives
US4083853A (en) * 1973-09-08 1978-04-11 Eisai Co., Ltd. 1,3-Benzodioxol derivatives
CH583730A5 (en) * 1973-09-25 1977-01-14 Wander Ag Dr A
US4025629A (en) * 1974-01-07 1977-05-24 The Upjohn Company P-(trifluoromethylquinolylamino)benzamides, pharmaceutical dosage forms and method of treatment
DE2757506C2 (en) * 1977-12-22 1980-02-14 Haarmann & Reimer Gmbh, 3450 Holzminden Process for the preparation of Piperonylidencrotonsaureamiden
DE2757483C2 (en) * 1977-12-22 1980-02-28 Haarmann & Leimer Gmbh, 3450 Holzminden Process for the preparation of Il-peronylidenecrotonic acid amides
CU21107A3 (en) * 1978-02-10 1988-02-01 Hoffmann La Roche DERIVATIVE PYRROLIDINES
US4209517A (en) * 1978-07-17 1980-06-24 Unicler α-Ethylenic alcohols and ketones, their preparation, and their use as medicaments
FR2461710A1 (en) * 1979-07-16 1981-02-06 Sarget Sa Labo NEW IMINES DERIVED FROM AMINO-5-BENZODIOXOLE-1,3 USEFUL AS MEDICINES
DE3009542A1 (en) * 1980-03-13 1981-09-24 Henkel KGaA, 4000 Düsseldorf DESODORING COSMETIC COMPOSITIONS
CH646149A5 (en) * 1981-02-05 1984-11-15 Hoffmann La Roche PYRROLIDINE DERIVATIVE.
US4431662A (en) * 1981-03-06 1984-02-14 Hodgson Gordon L Jun 1-(1,3-Benzodioxol-5-yl)-2-pyrrolidinone and its medicinal use
ES8203877A1 (en) * 1981-05-13 1982-04-01 Ferrer Int Process for producing 1-position amino-derivatives of 1-(3',4'-methylenedioxyphenyl)propane-2-ol
US4438142A (en) * 1982-03-05 1984-03-20 Burroughs Wellcome Co. Pharmaceutical combination
US4548949A (en) * 1983-01-24 1985-10-22 Syntex (U.S.A.) Inc. +2-[(3,4-Methylenedioxy)phenethyl]-5-[(3-carboxamido-4-hydroxy)-α-hydroxybenzyl]pyrrolidines
US4543361A (en) * 1983-08-29 1985-09-24 Muchowski Joseph M ±2-[Phenethyl]-5-[(3,4-methylenedioxy)-α-hydroxybenzyl]pyrrolidine antihypertensives and use thereas
US4499100A (en) * 1983-05-18 1985-02-12 Syntex (U.S.A.) Inc. Benzodioxanyl-hydroxyethyleneamino-piperidinyl acetanilides, ketones, esters and carbamates which effect immunity and calcium entry and β-blockade
US4582909A (en) * 1984-02-02 1986-04-15 Warner-Lambert Company Benzobicyclic lactam acids and derivatives as cognition activators
JPS60163812A (en) * 1984-02-03 1985-08-26 Zenyaku Kogyo Kk Antiallergic agent
IT1215587B (en) * 1987-06-26 1990-02-14 Roussel Maestretti Spa DERIVATIVES OF 1-BENZOIL2-OXO 5-ALCOSSI PIRROLIDINA, THEIR PREPARATION PROCEDURE AND THEIR USE AS A MEDICINAL SUBSTANCE.
US5284876A (en) * 1988-02-26 1994-02-08 Neuromedica, Inc. Method of treating tardive dyskinesia using dopaminergic agents of prodrugs of therapeutic agents
JPH02124884A (en) * 1988-07-08 1990-05-14 Zhongguo Yixuekexueyuan Yaowo Yanjiusuo N-substituted amide derivative
JP2842888B2 (en) * 1989-05-19 1999-01-06 森永製菓株式会社 Cancer cell metastasis inhibitor containing ribonuclease inhibitor as active ingredient
IT1231921B (en) * 1989-06-12 1992-01-15 Sigma Tau Ind Farmaceuti 1-ACIL-2-PYROLIDONES AS ACTIVATORS OF LEARNING PROCESSES AND MEMORY AND PHARMACEUTICAL COMPOSITIONS INCLUDING SUCH COMPOUNDS
SE464275B (en) * 1989-07-31 1991-04-08 Aagerup Bengt NEW USE OF BETA-RECEPTOR BLOCKER FOR PREPARING A PREPARATION FOR MENIER'S DISEASE
US5132119A (en) * 1989-07-31 1992-07-21 Massachusetts Institute Of Technology Treatment of hypertrophic wound healing disorders with calcium channel blockers
IE910939A1 (en) * 1990-04-13 1991-10-23 Neurosearch As Use of benzodiazepine compounds
FR2669029B1 (en) * 1990-11-14 1994-09-02 Adir NOVEL N-BENZOYL PROLINE DERIVATIVES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
DE69221175T2 (en) * 1991-02-07 1998-01-15 Roussel Uclaf Bicyclic nitrogen compounds, their preparation, intermediates obtained, their use as medicaments and pharmaceutical compositions containing them
US5070101A (en) * 1991-02-14 1991-12-03 Mount Sinai School Of Medicine Of The City University Of New York Method and pharmaceutical composition for the treatment of schizophrenia
US5104877A (en) * 1991-02-25 1992-04-14 Abbott Laboratories Psoriasis treatment
US5336675A (en) * 1991-05-14 1994-08-09 Ernir Snorrason Method of treating mania in humans
US5312817A (en) * 1991-05-14 1994-05-17 Ernir Snorrason Treatment of fatigue syndrome
DE4119146C2 (en) * 1991-06-11 2001-01-11 Rehau Ag & Co Polymer blends Process for their preparation and their use
US5298506A (en) * 1992-05-08 1994-03-29 Brigham And Women's Hospital Use of guanylate cyclase inhibitors in the treatment of shock
US6406868B1 (en) * 1992-06-10 2002-06-18 Nps Allelix Corporation AMPA-binding human GluR1 receptors
DK1156043T3 (en) 1992-07-24 2004-03-01 Univ California Drugs that enhance synaptic responses mediated by ampa receptors
US5385940A (en) * 1992-11-05 1995-01-31 The General Hospital Corporation Treatment of stroke with nitric-oxide releasing compounds
US5488049A (en) * 1993-12-10 1996-01-30 Fidia - Georgetown Institute For The Neuro-Sciences Method of treating learning and memory disorders using benzothiadiazide derivatives as nootropic agents
US6329364B1 (en) * 1994-08-31 2001-12-11 Eli Lilly And Company Crystalline form of dihydro-2,3-benzodiazepine derivative
US5852008A (en) 1995-01-24 1998-12-22 The Regents Of The University Of California Heteroatom substituted benzoyl derivatives that enhance synaptic response mediated by receptors
US5773434A (en) 1995-08-30 1998-06-30 Gary A. Rogers Facilitation of AMPA receptor-mediated synaptic transmission in brain as a treatment for schizophrenia
AU745641B2 (en) 1997-10-27 2002-03-28 Cortex Pharmaceuticals, Inc. Treatment of schizophrenia with ampakines and neuroleptics

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