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WO1994021244A1 - Procede de traitement de comportements de dependance - Google Patents

Procede de traitement de comportements de dependance Download PDF

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Publication number
WO1994021244A1
WO1994021244A1 PCT/US1994/002875 US9402875W WO9421244A1 WO 1994021244 A1 WO1994021244 A1 WO 1994021244A1 US 9402875 W US9402875 W US 9402875W WO 9421244 A1 WO9421244 A1 WO 9421244A1
Authority
WO
WIPO (PCT)
Prior art keywords
serotonin
agonist
dopamine
behavior
pharmaceutical composition
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1994/002875
Other languages
English (en)
Inventor
Pietr Hitzig
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Priority to AU64103/94A priority Critical patent/AU6410394A/en
Priority to CA002158173A priority patent/CA2158173C/fr
Priority to EP94911627A priority patent/EP0710106A4/fr
Publication of WO1994021244A1 publication Critical patent/WO1994021244A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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

  • Alcohol dependence one form of addictive behavior, is one of the most preventable and treatable current health problems. Although existing treatments of alcoholism can be effective they are not suited to all patients and often result in abstinence or non-hazardous drinking for a short time. Medications offer one way to improve the treatment of alcoholics. To this end I have devised and hereby disclose a form of therapy that is effective in reducing and often eliminating the craving and use of alcohol as well as other substances of abuse.
  • NAC neuronal modulation ooff hhuunnggeerr aanndd ssaattiiaattiioonn.. 1 144 BBootthh ⁇ cravings are modestly ameliorated by serotonin agonists.
  • the serotonin agonists have been used to treat patients with addictive behaviors as have the dopamine agonists, both individually, and both with variable results.
  • a serotonin agonist and a dopamine agonist preferably administered at the same time and desirably administered in the same dosage unit (tablet, capsule, solution), provides highly effective, predictable therapy for patients suffering from forms of addictive behavior as illustrated below in the treatment of alcoholism.
  • the serotonin agonist(s) and dopamine agonist(s) are administered in the same unit dosage or pharmaceutical presentation.
  • Current information indicates the use of a serotonergic drug reduces the potentially addictive qualities of dopaminergic drugs.
  • Presentation in a single unit, desirably thoroughly blended together in a pharmaceutically stable combination renders the potential for the separation of and possible abuse of the dopamine agonist far less likely.
  • This aspect of the invention is particularly important in rendering the product administered unattractive to potential or current amphetamine addicts and thus reduces the potential for abuse.
  • Suitable formulations include those suitable for oral, rectal and parenteral (including subcutaneous, intradermal, intramuscular and intravenous) administration.
  • the formulation may, where appropriate, be conveniently presented in discrete dosage units and may be prepared by any of the methods well known in the art of pharmacy.
  • Therapeutic formulations suitable for oral administration in which the carrier is a solid are most preferably presented as unit dose formulations such as boluses, capsules or tablets each containing a predetermined amount of the active ingredients.
  • a tablet may be made by compression or molding, optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing in a suitable machine the active ingredients in a free-flowing form such as a powder or granules optionally mixed with a binder, lubricant, inert diluent, lubricating agent, surface-active agent or dispersing agent. Molded tablets may be made by molding active ingredients with an inert liquid diluent.
  • Tablets may be optionally coated and, if uncoated, may optionally be scored.
  • Capsules may be prepared by filling the active ingredients, either alone or in admixture with one or more accessory ingredients, into the capsule shells and then sealing them in the usual manner. Cachets are analogous to capsules in which the active ingredient together with any accessory ingredient(s) is sealed in a rice paper envelope.
  • Formulations of the invention also include dispersible granules, which may for example be suspended in water before administration, or sprinkled on food.
  • the granules may be packaged, e.g. in a sachet.
  • Formulations suitable for oral administration where the carrier is a liquid may be presented as a solution or a suspension in an aqueous liquid or a non-aqueous liquid, or as an oil-in-water liquid emulsion.
  • Formulations for oral administration include controlled release dosage forms, e.g. tablets where the active ingredients are formulated in an appropriate release - controlling matrix, or are coated with a suitable release - controlling film.
  • Therapeutic formulations suitable for rectal administration where the carrier is a solid are most preferably presented as unit dose suppositories.
  • Suitable carriers include cocoa butter and other materials commonly used in the art.
  • the suppositories may be conveniently formed by admixture of the active ingredients with the softened or melted carrier(s) followed by chilling and shaping in molds.
  • Therapeutic formulations suitable for parenteral administration include sterile solutions or suspensions of the active ingredients in aqueous or oleaginous vehicles.
  • Injectable preparations may be adapted for bolus injection or continuous infusion. Such preparations are conveniently presented in unit dose or multi-dose containers which are sealed after introduction of the formulation until required for use.
  • the active ingredient may be in powder form which is constituted with a suitable vehicle, such as sterile, pyrogen-free water, before use.
  • depot preparations may be administered by intramuscular injection or by implantation, e.g. subcutaneously or intramuscularly.
  • Depot preparations may include, for example, suitable polymeric or hydrophobic materials, or ion-exchange resins. Such long-acting formulations are particularly convenient for prophylactic use.
  • the therapeutic formulations for the various routes of administration described above may include, as appropriate one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like, and substances included for the purpose of rendering the formulation isotonic with the blood of the intended recipient.
  • additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like, and substances included for the purpose of rendering the formulation isotonic with the blood of the intended recipient.
  • compositions of the present invention may be administered in combination or concurrently with other therapeutic agents.
  • serotonin agonists and dopamine agonist may be considered for use in the therapeutic methods and pharmaceutical compositions of the invention.
  • the following is a non-limiting partial listing of products currently approved for use in the United States or other countries or in the final stages of regulatory approval.
  • Amphetamines At high doses cause release of dopamine from dopaminergic nerve terminals, particularly in the neostriatum. At still higher doses, cause release of 5-hydroxy-tryptamine (5-HT) and dopamine in the mesolimbic system.
  • 5-hydroxy-tryptamine 5-HT
  • Phendimetrazine (Phenazine®)
  • Tricyclic antidepressants and other antidepressants block the reuptake of serotonin, dopamine, and/or norepinephrine at the neuronal membrane. The degree of potency and selectivity vary greatly among these agents.
  • Monoamine Oxidase (MAO) Inhibitors block deamination of dopamine and serotonin.
  • Dopamine Agonists immediate metabolic precursor of dopamine in the basal ganglia; or release of dopamine from central neurons in the basal ganglia (i.e., nigrostriatal neurons) .
  • Buspirone (Buspar®) -- appears to act as a mixed agonist/antagonist at both the dopaminergic and serotonin receptors.
  • Lithium (Eskalith®) -- enhances the release of serotonin, especially in the hippocampus and may alter reuptake of catecholamines (i.e., dopamine).
  • Nicotine (NicoretteR, HabitrolR patch) -- stimulates release of norepinephrine and dopamine from brain tissue.
  • Phencyclidine inhibits reuptake of dopamine, serotonin, and norepinephrine by synapses.
  • Lysergic Acid -- serotonin agonist Lysergic Acid -- serotonin agonist
  • Reserpine Ser-Ap-EsR -- inhibit reuptake of dopamine and serotonin, resulting in depletion of stores.
  • Tryptophan a precursor of serotonin.
  • Fenfluramine is a racemic mixture of a drug which releases serotonin to the central and peripheral nervous system and inhibits serotonin re-uptake into the neuron. Either optical isomer or a racemic mixture may be used. Preferably the amount administered is from 10 to 90 mg/day in single or divided doses.
  • Phentermine is an adrenergic compound structurally related to amphetamines. Such agents typically increase dopamine and nor adrenaline concentrations at their respective receptor sites in the brain. Preferably the daily amount administered is 15 to 160 mg in single or divided doses.
  • Phentermine and racemic fenfluramine treatment was given to twelve alcoholic patients. Eleven of twelve consecutive patients, most within hours, have noted a total loss or marked decrease in alcohol craving. Their consumption of alcohol has ceased or decreased markedly.
  • This treatment is successful because of the dual and balanced increase in the bioavailability of the neurotransmitters dopamine and serotonin in the nucleus accumbens.
  • Other addictive behaviors susceptible to such treatment with dual aminergic agonists may include cocaine, nicotine, narcotic and amphetamine addiction as well as depression and various presentations of obsessive compulsive behavior.
  • compositions were prepared containing 80 mg. of fenfluramine hydrochloride and 30 mg. of phentermine hydrochloride powders distributed in a diluent of hydroxypropylmethyl cellulose (45 mg) . The mixture was placed in a No. 1 capsule.
  • Ms A a successful non-obese executive in her late twenties is the progeny of two alcoholics.
  • Ms A has had a stormy alcoholic history. She reports that for years she had been binge drinking despite Alcoholics Anonymous meetings.
  • Ms A suffered from ever present alcohol craving and obsessional ideation relieved only by alcohol.
  • Her employers understandably, have arrived whether they can continue to employ her.
  • Mr- C early sixties, started the medication eight weeks ago. He also has had complete loss of craving and is no longer drinking spirits. If he drinks at all, he limits it to a can or two of beer. He has started a support group which will help new people on the protocol.

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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)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne le traitement de comportements de dépendance, de comportements dépressifs ou maniaco-dépressifs, à l'exclusion de l'obésité, où on administre à un patient une quantité efficace d'au moins un agoniste de sérotonine et d'au moins un agoniste de dopamine. La combinaison de l'agoniste de sérotonine et de l'agoniste de dopamine est présente en quantité efficace pour traiter le comportement de dépendance du patient. L'invention concerne également des compositions pharmaceutiques.
PCT/US1994/002875 1993-03-17 1994-03-17 Procede de traitement de comportements de dependance Ceased WO1994021244A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU64103/94A AU6410394A (en) 1993-03-17 1994-03-17 Method of treating addictive behaviors
CA002158173A CA2158173C (fr) 1993-03-17 1994-03-17 Methode pour le traitement de comportements de dependance
EP94911627A EP0710106A4 (fr) 1993-03-17 1994-03-17 Procede de traitement de comportements de dependance

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3483493A 1993-03-17 1993-03-17
US034,834 1993-03-17

Publications (1)

Publication Number Publication Date
WO1994021244A1 true WO1994021244A1 (fr) 1994-09-29

Family

ID=21878899

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/002875 Ceased WO1994021244A1 (fr) 1993-03-17 1994-03-17 Procede de traitement de comportements de dependance

Country Status (4)

Country Link
EP (1) EP0710106A4 (fr)
AU (1) AU6410394A (fr)
CA (1) CA2158173C (fr)
WO (1) WO1994021244A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998037876A1 (fr) * 1997-02-28 1998-09-03 Adir Et Compagnie Composition pharmaceutique pour la liberation programmee de dexfenfluramine
US6056715A (en) * 1995-12-12 2000-05-02 Omeros Medical Systems, Inc. Surgical irrigation solution and method for inhibition of pain and inflammation
US6413961B1 (en) 1995-12-12 2002-07-02 Omeros Medical Systems, Inc. Irrigation solution and method for inhibition of pain and inflammation
WO2009091605A3 (fr) * 2008-01-17 2009-10-22 Health Innovations, Llc Traitements de titration du goût
US7632859B2 (en) 2002-12-02 2009-12-15 Schwarz Pharma Ag Iontophoretic delivery of rotigotine for the treatment of Parkinson's disease
US8754119B2 (en) 2003-07-26 2014-06-17 Ucb Pharma Gmbh Use of rotigotine for the treatment of depression
US9220715B2 (en) 2010-11-08 2015-12-29 Omeros Corporation Treatment of addiction and impulse-control disorders using PDE7 inhibitors
RU2661410C2 (ru) * 2010-11-08 2018-07-16 Омерос Корпорейшн Лечение зависимости и расстройства побуждений с применением ингибиторов фдэ7

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4255439A (en) * 1979-07-13 1981-03-10 Irving Cooper Means and method for aiding individuals to stop smoking

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4255439A (en) * 1979-07-13 1981-03-10 Irving Cooper Means and method for aiding individuals to stop smoking

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BIOSIS ABSTRACTS 9549752, issued 1992, WEINTRAUB et al.: "Long-term weight control study...", see abstract No. 94054752, CLIN. PHARMACOL THER, 51(5), 586-594. *
See also references of EP0710106A4 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6056715A (en) * 1995-12-12 2000-05-02 Omeros Medical Systems, Inc. Surgical irrigation solution and method for inhibition of pain and inflammation
US6242447B1 (en) 1995-12-12 2001-06-05 Omeros Medical Systems, Inc. Surgical irrigation solution and method for inhibition of pain and inflammation
US6261279B1 (en) 1995-12-12 2001-07-17 Omeros Medical Systems, Inc. Surgical irrigation solution and method for inhibition of pain and inflammation
US6413961B1 (en) 1995-12-12 2002-07-02 Omeros Medical Systems, Inc. Irrigation solution and method for inhibition of pain and inflammation
FR2760190A1 (fr) * 1997-02-28 1998-09-04 Adir Composition pharmaceutique pour la liberation programmee de dexfenfluramine
WO1998037876A1 (fr) * 1997-02-28 1998-09-03 Adir Et Compagnie Composition pharmaceutique pour la liberation programmee de dexfenfluramine
US7632859B2 (en) 2002-12-02 2009-12-15 Schwarz Pharma Ag Iontophoretic delivery of rotigotine for the treatment of Parkinson's disease
US8754119B2 (en) 2003-07-26 2014-06-17 Ucb Pharma Gmbh Use of rotigotine for the treatment of depression
US8137690B2 (en) 2008-01-17 2012-03-20 Health Innovations, Llc Taste titration therapies
WO2009091605A3 (fr) * 2008-01-17 2009-10-22 Health Innovations, Llc Traitements de titration du goût
US9220715B2 (en) 2010-11-08 2015-12-29 Omeros Corporation Treatment of addiction and impulse-control disorders using PDE7 inhibitors
RU2661410C2 (ru) * 2010-11-08 2018-07-16 Омерос Корпорейшн Лечение зависимости и расстройства побуждений с применением ингибиторов фдэ7
US11207275B2 (en) 2010-11-08 2021-12-28 Omeros Corporation Treatment of addiction and impulse-control disorders using PDE7 inhibitors
US11464785B2 (en) 2010-11-08 2022-10-11 Omeros Corporation Treatment of addiction and impulse-control disorders using PDE7 inhibitors

Also Published As

Publication number Publication date
EP0710106A4 (fr) 1999-07-21
AU6410394A (en) 1994-10-11
CA2158173A1 (fr) 1994-09-29
EP0710106A1 (fr) 1996-05-08
CA2158173C (fr) 2001-12-04

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