WO1992021333A2 - Traitement des symptomes de sevrage et de manque dus a des drogues au moyen d'inhibiteurs d'oxydase de monoamine de type b - Google Patents

Traitement des symptomes de sevrage et de manque dus a des drogues au moyen d'inhibiteurs d'oxydase de monoamine de type b Download PDF

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Publication number
WO1992021333A2
WO1992021333A2 PCT/US1992/003702 US9203702W WO9221333A2 WO 1992021333 A2 WO1992021333 A2 WO 1992021333A2 US 9203702 W US9203702 W US 9203702W WO 9221333 A2 WO9221333 A2 WO 9221333A2
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WO
WIPO (PCT)
Prior art keywords
type
monoamine oxidase
withdrawal symptoms
craving
oxidase inhibitor
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PCT/US1992/003702
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English (en)
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WO1992021333A3 (fr
Inventor
George W. Belendiuk
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Pharmavene, Inc.
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Publication date
Application filed by Pharmavene, Inc. filed Critical Pharmavene, Inc.
Publication of WO1992021333A2 publication Critical patent/WO1992021333A2/fr
Publication of WO1992021333A3 publication Critical patent/WO1992021333A3/fr

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    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline

Definitions

  • This invention relates to the treatment of substance abuse or addiction; in particular, to the treatment of withdrawal symptoms and to the prevention or reduction of drug craving in patients undergoing treatment for abuse of or addiction to various drugs, such as addictive psychostimulants, addictive opiates, alcohol, and nicotine. More particularly, this invention relates to the treatment of withdrawal symptoms and the prevention or reduction of drug craving through the use of Type B monoamine oxidase (MAO) inhibitors.
  • MAO monoamine oxidase
  • Cessation of the use of addictive drugs may result in a variety of undesirable physical and/or psychological symptoms.
  • Such symptoms may include drug craving, depression, irritability, anergia, amotivation, appetite changes, nausea, shaking, psychomotoric retardation, and irregular sleep patterns, such as, for example, hypersomnia. Relief of such symptoms would aid patients in stopping the use of addicting drugs more easily and would also be useful in the post-drug recovery period.
  • a method of treating withdrawal symptoms and preventing or reducing craving of addictive psychostimulants comprises administering to a patient at least one Type B
  • SUBSTITUTESHEET monoamine oxidase inhibitor (sometimes hereinafter referred to as a Type B MAO inhibitor or an MAO B inhibitor) in an amount effective to alleviate withdrawal symptoms and to prevent or reduce craving of addictive psychostimulants in a patient.
  • Type B monoamine oxidase inhibitors are converted by monoamine oxidase to an active moiety which combines irreversibly with the active site and/or the enzyme's essential FAD cofactor. Because such Type B MAO inhibitors have greater affinity for Type B active sites than for Type A active sites, such Type B MAO inhibitors can act as selective inhibitors of MAO Type B.
  • a Type B MAO inhibitor may be determined by measuring MAO activity of the following samples:
  • a biological sample eg., a brain tissue sample or blood sample
  • no MAO inhibitors are added.
  • clorgyline is a highly selective Type A MAO inhibitor, one can determine the proportion of total MAO activity which is Type A MAO activity and the proportion of MAO activity which is Type B MAO activity. If the sum of the MAO inhibitory activities of clorgyline used alone and of the substance being tested for selective Type B MAO inhibition used alone is greater than 100%, then the substance being tested for Type B MAO inhibition is not a selective inhibitor of Type B MAO. If the sum of the MAO inhibitory activities of clorgyline used alone and of the substance being tested for selective Type B MAO inhibition used alone approaches but does not exceed 100%, and the MAO inhibitory activity of a combination of clorgyline and the test
  • test substance is a selective Type B MAO inhibitor.
  • An example of an assay procedure for determining MAO with applications for determining Type B MAO inhibitors may be found in Belendiuk, et al., "Platelet Serotonin and Platelet MAO Activity in Individuals with Huntington's Disease," in Chase, et al., eds., Advances in Neurology, New York (1979).
  • the at least one Type B monoamine oxidase inhibitor is selected from the group consisting of deprenyl, AGN-1135, MDL72145, and J-508.
  • the at least one Type B monoamine oxidase inhibitor is deprenyl.
  • Deprenyl exists in the forms of optical isomers; i.e., a D-isomer and an L-isomer. Most preferably, deprenyl is administered in the form of the L-isomer, also known as selegiline. Deprenyl has the following structural formula:
  • selegiline may be administered in the form of selegiline hydrochloride (selegiline HC1).
  • AGN-1135 is further described in Youdim, et al., Adv. Neurol. , Vol. 45, pgs. 127-36 (1987); MDL-72145 is further described in Fozard, et al., Naunvn Schmiedebergs Arch. Pharmacol. , Vol. 331, pgs. 186-193 (1985); and J-508 is further described in Knoll, et al., Biochem. Pharmacol., Vol. 27, pgs. 1739-1747 (1978) and Bey, et al. , Br. J. Pharmacol., Vol. 8_ , pg. 50 (1984).
  • the at least one Type B monoamine oxidase inhibitor in general, may be administered in an amount of from about 0.05 mg to about 20 mg per day, preferably from about 5.0 mg to about 10 mg per day.
  • the at least one Type B monoamine oxidase inhibitor may be administered in a single dosage, or in multiple dosages administered at regular intervals.
  • SUBSTITUTESHEET monoamine oxidase inhibitor may be administered in accordance with a patient's individual requirements.
  • the at least one Type B monoamine oxidase inhibitor may be administered in free base form or in a pharmaceutically acceptable salt form.
  • the at least one Type B monoamine oxidase inhibitor may be administered orally or parenterally.
  • the at least one Type B monoamine oxidase inhibitor may be administered in a variety of forms, such as tablets, powders, granules, capsules, syrups, and elixirs. Such forms may also include acceptable pharmaceutical carriers such as diluents, granulating agents, disintegrating agents, and lubricating agents.
  • the tablet When a tablet is employed, the tablet may be uncoated or coated by techniques known to those skilled in the art to delay disintegration and absorption in the gastrointestinal tract to provide a sustained action over an extended period.
  • the preparation of the orally administrable forms will be apparent to those of ordinary skill in the art from the teachings contained herein.
  • the at least one Type B monoamine oxidase inhibitor may be administered parenterally, such as, for example, in the form of an aqueous in ectable solution, which may be administered intramuscularly or intravenously. It is also contemplated that within the scope of the present invention that the at least one Type B monoamine oxidase inhibitor may be administered transdermally, such as for example, in a matrix adhesive patch; bucally, or intranasally by administering the at least one Type B monoamine oxidase inhibitor with conventional pharmaceutically carriers or excipients such as, for example, permeation enhancers. It is to be understood, however, that the scope of the present invention is not to be limited to any particular form of administration.
  • Addictive psychostimulants to which this aspect of the present invention is applicable include, but are not limited to, cocaine, amphetamines, methamphetamines, dextroamphetamines,
  • SUBSTITUTESHEET chlorphentermine methylphenidate, pipradrol, p-hydroxymorphedrine, fenfluramine, 1-(2,5-di-methoxy-4 methylphenyl)-2-aminopropane (DOM), bupropion, pemoline, and analogues or derivatives thereof, such as the phosphate, sulfate, and 4-chlorophenoxy-acetate salts of amphetamines, methamphetamines, dextroamphetamines, and pemoline.
  • Addictive psychostimulants are further described in Glennon, "Psychoactive Phenylisopropylamines, " in Meltzer, ed., Psychopharmacology: The Third Generation of Progress, Raven Press, New York (1987).
  • the present invention is particularly applicable to the treatment of patients undergoing treatment for cocaine addiction whereby the administration of at least one Type B monoamine oxidase inhibitor is employed to alleviate withdrawal symptoms associated with the cessation of cocaine use and/or prevent or reduce cocaine craving.
  • a method of treating withdrawal symptoms and for preventing, or reducing craving of addictive opiates comprises administering to a patient at least one Type B monoamine oxidase inhibitor in an amount effective to alleviate withdrawal symptoms and/or prevent or reduce craving of addictive opiates in a patient.
  • the at least one Type B monoamine oxidase inhibitor may be as hereinabove described, and may be administered in amounts hereinabove described as well.
  • Addictive opiates to which this aspect of the present invention is applicable include, but are not limited to, opium, including powdered opium, granulated opium, raw opium, tincture of opium, and opium fluid extracts; morphine and derivatives thereof, such as, for example, ethylmorphine; heroin and derivatives thereof.
  • a method of treating withdrawal symptoms and for preventing or reducing craving of alcohol by administering to a patient at least one Type B monoamine oxidase
  • SUBSTITUTE SHEET inhibitor such as those hereinabove described, in an amount effective to alleviate withdrawal symptoms and prevent or reduce craving of alcohol in a patient.
  • the at least one Type B monoamine oxidase inhibitor may be administered in amounts and in forms such as those hereinabove described.
  • a method of treating withdrawal symptoms and for preventing craving of nicotine comprises administering to a patient at least one Type B monoamine oxidase inhibitor in an amount effective to alleviate withdrawal symptoms and prevent or reduce craving of nicotine in a patient.
  • the at least one Type B monoamine oxidase inhibitor may be administered in amounts and in forms such as those hereinabove described.
  • the methods of the present invention may be employed in conjunction with other means of treatment such as, for example, behavioral or psychological or psychiatric treatment provided by inpatient or outpatient substance abuse programs.
  • selegiline is administered in the form of a tablet containing 5 mg of selegiline hydrochloride, and the inactive ingredients lactose, starch, povidone, magnesium stearate, and talc.
  • a tablet is sold under the trade name Eldepryl by Somerset Pharmaceuticals, Inc., of Denville, New Jersey.
  • the tablet is administered to a patient undergoing treatment for psychostimulant addiction, opiate addiction, alcohol abuse, or nicotine abuse.
  • the tablet is administered twice daily for six weeks.
  • the materials and methods of the present invention may also be employed in treating withdrawal symptoms associated with and for preventing craving of addictive narcotics and of addictive barbiturates.
  • addictive narcotics include, but are not limited to, those commonly prescribed for pain and discomfort such as alphaprodine; anileridine; bezitramide;
  • SUBSTITUTESHEET codeine dihydrocodeine; diphenoxylate; fentanyl; hydrocodone; hydrormorphone; isomethadone; levo ethorphan; levorphanol; metazocine; methadone; metopon; oxycodone; oxymorphone; pethidine; phenazocine; piminodine; racemethorphan; racemorphan; thebaine, or pharmaceutically acceptable salts thereof.
  • addictive barbiturates include, but are not limited to, allobarbital; amylbarbital; butabarbital; hexobarbital; mephobabital; methohexital; pentobarbital; phenobarbital; phenethylbarbital; secobarbital; talbutal; and thiopental.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Procédés de traitement des symptômes de sevrage et de prévention ou de diminution du manque de psychostimulants créant une accoutumance (par exemple, la cocaïne), des opiacés, de l'alcool ou de la nicotine, au moyen de l'administration à un patient d'un inhibiteur d'oxydase de monoamine de type B, en quantité efficace pour atténuer les symptômes de sevrage et supprimer ou diminuer le manque de psychostimulants créant une accoutumance, d'opiacés, d'alcool ou de nicotine. Un inhibiteur d'oxydase de monoamine de type B est le L-deprenyl ou la sélégiline.
PCT/US1992/003702 1991-05-24 1992-05-04 Traitement des symptomes de sevrage et de manque dus a des drogues au moyen d'inhibiteurs d'oxydase de monoamine de type b WO1992021333A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US70508591A 1991-05-24 1991-05-24
US705,085 1991-05-24

Publications (2)

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WO1992021333A2 true WO1992021333A2 (fr) 1992-12-10
WO1992021333A3 WO1992021333A3 (fr) 1993-01-07

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Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995015160A1 (fr) * 1993-11-30 1995-06-08 Saurat Jean Hilaire Utilisation de la selegiline et ses derives pour le traitement du psoriasis
DE19746191A1 (de) * 1997-10-18 1999-06-10 Lohmann Therapie Syst Lts Verfahren zur Anwendung eines Wirkstoff enthaltenden Pflasters zur Bekämpfung oder Linderung einer Sucht
US5981598A (en) * 1995-02-10 1999-11-09 The University Of Toronto Innovations Foundation Deprenyl compounds for treatment of glaucoma
WO2000071109A2 (fr) * 1999-05-21 2000-11-30 Somerset Pharmaceuticals, Inc. S-(+)-desmethylselegiline et son utilisation therapeutique
US6280763B1 (en) 1999-05-10 2001-08-28 Pierce Management, Llc Apparatus and method for transdermal delivery of bupropion
US6299901B1 (en) 1995-01-13 2001-10-09 Somerset Pharmaceuticals, Inc. Methods and pharmaceutical compositions employing desmethylselegiline
US6316022B1 (en) 1995-06-07 2001-11-13 Noven Pharmaceuticals, Inc. Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures
US6419960B1 (en) 1998-12-17 2002-07-16 Euro-Celtique S.A. Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
US6673367B1 (en) 1998-12-17 2004-01-06 Euro-Celtique, S.A. Controlled/modified release oral methylphenidate formulations
EP1441708A1 (fr) * 2001-11-05 2004-08-04 Krele Pharmaceuticals LLC Compositions et methodes permettant d'augmenter l'observance therapeutique au moyen d'inhibiteurs de l'aldehyde deshydrogenase et traitement de l'alcoolisme
US6932971B2 (en) 2002-07-18 2005-08-23 Cytos Biotechnology Ag Hapten-carrier conjugates and uses thereof
US7083808B2 (en) 1998-12-17 2006-08-01 Euro-Celtique S.A. Controlled/modified release oral methylphenidate formulations
WO2008055945A1 (fr) 2006-11-09 2008-05-15 Probiodrug Ag Dérivés 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one utiles en tant qu' inhibiteurs de la glutaminyl-cyclase dans le traitement des ulcères, du cancer et d'autres maladies
WO2008065141A1 (fr) 2006-11-30 2008-06-05 Probiodrug Ag Nouveaux inhibiteurs de glutaminylcyclase
WO2008104580A1 (fr) 2007-03-01 2008-09-04 Probiodrug Ag Nouvelle utilisation d'inhibiteurs de la glutaminyl cyclase
US7732162B2 (en) 2003-05-05 2010-06-08 Probiodrug Ag Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
WO2011029920A1 (fr) 2009-09-11 2011-03-17 Probiodrug Ag Dérivés hétérocycliques en tant qu'inhibiteurs de glutaminyle cyclase
US7993671B2 (en) 1995-06-07 2011-08-09 Noven Pharmaceuticals, Inc. Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures
WO2011095973A1 (fr) 2010-02-03 2011-08-11 Pharma Two B Ltd. Formulations à libération prolongée de rasagiline et leurs utilisations
WO2011107530A2 (fr) 2010-03-03 2011-09-09 Probiodrug Ag Nouveaux inhibiteurs
WO2011110613A1 (fr) 2010-03-10 2011-09-15 Probiodrug Ag Inhibiteurs hétérocycliques de la glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (fr) 2010-04-21 2011-10-27 Probiodrug Ag Nouveaux inhibiteurs
EP2433626A1 (fr) 2003-11-25 2012-03-28 Technion Research & Development Foundation Ltd. Compositions et procédés pour le traitement des troubles cardiovasculaires et maladies
US8263655B2 (en) 2005-10-06 2012-09-11 Technion Research And Development Foundation Ltd Methods for treatment of renal failure
WO2012123563A1 (fr) 2011-03-16 2012-09-20 Probiodrug Ag Dérivés de benzimidazole en tant qu'inhibiteurs de la glutaminyl cyclase
US20130165511A1 (en) * 2010-09-01 2013-06-27 TONIX Pharmaceuticals Holding Corp Treatment for cocaine addiction
EP2865670A1 (fr) 2007-04-18 2015-04-29 Probiodrug AG Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase
CZ305817B6 (cs) * 1997-12-15 2016-03-23 Noven Pharmaceuticals, Inc. Směsi a metody pro léčení lehké mozkové dysfunkce a poruch deficitu pozornosti a hyperaktivity methylfenidátem
US9937144B2 (en) 2013-01-30 2018-04-10 The Johns Hopkins University Treatment of drug abuse by preventing GAPDH nitrosylation
US9974752B2 (en) 2014-10-31 2018-05-22 Purdue Pharma Methods and compositions particularly for treatment of attention deficit disorder
US10040975B2 (en) 2006-08-18 2018-08-07 Tesa Se Pressure-sensitive adhesive strip for moisture-insensitive peelable adhesive bonds
EP3461819A1 (fr) 2017-09-29 2019-04-03 Probiodrug AG Inhibiteurs de la glutaminyl-cyclase
US10722473B2 (en) 2018-11-19 2020-07-28 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder

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Cited By (74)

* Cited by examiner, † Cited by third party
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FR2713087A1 (fr) * 1993-11-30 1995-06-09 Saurat Jean Hilaire Utilisation de la sélégiline et ses dérivés pour la préparation d'un médicament destiné au traitement du psoriasis.
WO1995015160A1 (fr) * 1993-11-30 1995-06-08 Saurat Jean Hilaire Utilisation de la selegiline et ses derives pour le traitement du psoriasis
US6299901B1 (en) 1995-01-13 2001-10-09 Somerset Pharmaceuticals, Inc. Methods and pharmaceutical compositions employing desmethylselegiline
US6562364B2 (en) 1995-01-13 2003-05-13 Somerset Pharmaceuticals, Inc. Desmethylselegiline enantiomers and their use to treat drug withdrawal symptoms
US6420433B2 (en) 1995-01-13 2002-07-16 Somerset Pharmaceuticals, Inc. S(+) desmethylselegiline and drug withdrawal
US6319954B1 (en) 1995-01-13 2001-11-20 Somerset Pharmaceuticals, Inc. S-(+)-desmethylselegiline and its use in the therapeutic methods and pharmaceutical compositions
US5981598A (en) * 1995-02-10 1999-11-09 The University Of Toronto Innovations Foundation Deprenyl compounds for treatment of glaucoma
US6455590B1 (en) 1995-02-10 2002-09-24 University Of Toronto Innovations.Foundation Deprenyl compounds for treatment of glaucoma
EP1637170A1 (fr) 1995-06-07 2006-03-22 Noven Pharmaceuticals, Inc. Compositions transdermiques contenant des médicaments de faible poids moléculaire liquides à température ambiante
US8337884B2 (en) 1995-06-07 2012-12-25 Noven Pharmaceuticals, Inc. Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures
US7993671B2 (en) 1995-06-07 2011-08-09 Noven Pharmaceuticals, Inc. Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures
EP2258407A2 (fr) 1995-06-07 2010-12-08 Noven Pharmaceuticals, INC. Compositions transdermiques contenant des médicaments de faible poids moléculaire liquides à température ambiante
US6316022B1 (en) 1995-06-07 2001-11-13 Noven Pharmaceuticals, Inc. Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures
DE19746191A1 (de) * 1997-10-18 1999-06-10 Lohmann Therapie Syst Lts Verfahren zur Anwendung eines Wirkstoff enthaltenden Pflasters zur Bekämpfung oder Linderung einer Sucht
DE19746191C2 (de) * 1997-10-18 2000-05-18 Lohmann Therapie Syst Lts Verfahren zur Anwendung eines Wirkstoff enthaltenden Pflasters zur Bekämpfung oder Linderung einer Sucht
CZ305817B6 (cs) * 1997-12-15 2016-03-23 Noven Pharmaceuticals, Inc. Směsi a metody pro léčení lehké mozkové dysfunkce a poruch deficitu pozornosti a hyperaktivity methylfenidátem
US6673367B1 (en) 1998-12-17 2004-01-06 Euro-Celtique, S.A. Controlled/modified release oral methylphenidate formulations
US7438930B2 (en) 1998-12-17 2008-10-21 Purdue Pharma Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
US8580310B2 (en) 1998-12-17 2013-11-12 Purdue Pharma Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
US7083808B2 (en) 1998-12-17 2006-08-01 Euro-Celtique S.A. Controlled/modified release oral methylphenidate formulations
US6419960B1 (en) 1998-12-17 2002-07-16 Euro-Celtique S.A. Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
US7247318B2 (en) 1998-12-17 2007-07-24 Purdue Pharma Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
US10039719B2 (en) 1998-12-17 2018-08-07 Rhodes Pharmaceuticals L.P. Methods of treating attention deficit hyperactivity disorder
US10022330B2 (en) 1998-12-17 2018-07-17 Rhodes Pharmaceuticals L.P. Methods of preparing oral controlled release formulations
US9949931B2 (en) 1998-12-17 2018-04-24 Rhodes Pharmaceuticals L.P. Methods of treating attention deficit hyperactivity disorder
US10463624B2 (en) 1998-12-17 2019-11-05 Rhodes Pharmaceuticals L.P. Controlled release formulations
US9801823B2 (en) 1998-12-17 2017-10-31 Rhodes Pharmaceuticals L.P. Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
US9066869B2 (en) 1998-12-17 2015-06-30 Purdue Pharma Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations
US6280763B1 (en) 1999-05-10 2001-08-28 Pierce Management, Llc Apparatus and method for transdermal delivery of bupropion
WO2000071109A2 (fr) * 1999-05-21 2000-11-30 Somerset Pharmaceuticals, Inc. S-(+)-desmethylselegiline et son utilisation therapeutique
WO2000071109A3 (fr) * 1999-05-21 2001-03-01 Somerset Pharmaceuticals Inc S-(+)-desmethylselegiline et son utilisation therapeutique
EP1441708A1 (fr) * 2001-11-05 2004-08-04 Krele Pharmaceuticals LLC Compositions et methodes permettant d'augmenter l'observance therapeutique au moyen d'inhibiteurs de l'aldehyde deshydrogenase et traitement de l'alcoolisme
EP1441708A4 (fr) * 2001-11-05 2007-05-23 Krele Pharmaceuticals Llc Compositions et methodes permettant d'augmenter l'observance therapeutique au moyen d'inhibiteurs de l'aldehyde deshydrogenase et traitement de l'alcoolisme
US8093300B2 (en) 2001-11-05 2012-01-10 Krele Pharmaceuticals, Inc. Compositions and methods for increasing compliance with therapies using aldehyde dehydrogenase inhibitors and treating alcoholism
US8481599B2 (en) * 2001-11-05 2013-07-09 Tonix Pharmaceuticals Inc. Compositions and methods for increasing compliance with therapies using aldehyde dehydrogenase inhibitors and treating alcoholism
US20120101154A1 (en) * 2001-11-05 2012-04-26 Tonix Pharmaceuticals, Inc. Compositions and methods for increasing compliance with therapies using aldehyde dehydrogenase inhibitors and treating alcoholism
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US8809010B2 (en) 2003-05-05 2014-08-19 Probiodrug Ag Method for prophylactic treatment of alzheimer's disease using inhibitors of glutaminyl cyclase and glutamate cyclases
US7732162B2 (en) 2003-05-05 2010-06-08 Probiodrug Ag Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
EP2433626A1 (fr) 2003-11-25 2012-03-28 Technion Research & Development Foundation Ltd. Compositions et procédés pour le traitement des troubles cardiovasculaires et maladies
US8263655B2 (en) 2005-10-06 2012-09-11 Technion Research And Development Foundation Ltd Methods for treatment of renal failure
US10040975B2 (en) 2006-08-18 2018-08-07 Tesa Se Pressure-sensitive adhesive strip for moisture-insensitive peelable adhesive bonds
WO2008055945A1 (fr) 2006-11-09 2008-05-15 Probiodrug Ag Dérivés 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one utiles en tant qu' inhibiteurs de la glutaminyl-cyclase dans le traitement des ulcères, du cancer et d'autres maladies
WO2008065141A1 (fr) 2006-11-30 2008-06-05 Probiodrug Ag Nouveaux inhibiteurs de glutaminylcyclase
WO2008104580A1 (fr) 2007-03-01 2008-09-04 Probiodrug Ag Nouvelle utilisation d'inhibiteurs de la glutaminyl cyclase
EP2481408A2 (fr) 2007-03-01 2012-08-01 Probiodrug AG Nouvelle utilisation d'inhibiteurs glutaminyle cyclase
EP2865670A1 (fr) 2007-04-18 2015-04-29 Probiodrug AG Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase
WO2011029920A1 (fr) 2009-09-11 2011-03-17 Probiodrug Ag Dérivés hétérocycliques en tant qu'inhibiteurs de glutaminyle cyclase
WO2011095973A1 (fr) 2010-02-03 2011-08-11 Pharma Two B Ltd. Formulations à libération prolongée de rasagiline et leurs utilisations
EP3517103A1 (fr) 2010-02-03 2019-07-31 Pharma Two B Ltd. Formulations de rasagiline à libération prolongée et leurs utilisations
WO2011107530A2 (fr) 2010-03-03 2011-09-09 Probiodrug Ag Nouveaux inhibiteurs
WO2011110613A1 (fr) 2010-03-10 2011-09-15 Probiodrug Ag Inhibiteurs hétérocycliques de la glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (fr) 2010-04-21 2011-10-27 Probiodrug Ag Nouveaux inhibiteurs
EP3170499A1 (fr) 2010-09-01 2017-05-24 Tonix Pharmaceuticals, Inc. Traitement contre la cocaïnomanie
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WO1992021333A3 (fr) 1993-01-07

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