WO2001022820A1 - Use of pramipexole as a treatment for cocaine craving - Google Patents

Use of pramipexole as a treatment for cocaine craving Download PDF

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Publication number
WO2001022820A1
WO2001022820A1 PCT/US2000/026634 US0026634W WO0122820A1 WO 2001022820 A1 WO2001022820 A1 WO 2001022820A1 US 0026634 W US0026634 W US 0026634W WO 0122820 A1 WO0122820 A1 WO 0122820A1
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Prior art keywords
hydrochloride
treatment
pramipexole
cocaine
craving
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PCT/US2000/026634
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French (fr)
Inventor
Jerrold Rosenbaum
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The General Hospital Corporation
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Publication date
Application filed by The General Hospital Corporation filed Critical The General Hospital Corporation
Priority to AU76206/00A priority Critical patent/AU7620600A/en
Priority to CA002384840A priority patent/CA2384840A1/en
Priority to US10/088,628 priority patent/US6750235B1/en
Publication of WO2001022820A1 publication Critical patent/WO2001022820A1/en

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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine

Definitions

  • This invention relates to methods for the treatment of cocaine craving.
  • Cocaine is a highly addictive pyschostimulant that causes sensations of euphoria and craving, resulting in physiological as well as psychological damage.
  • cocaine use leads to a multitude of physiological complications, its primary target of action is the central nervous system.
  • Cocaine withdrawal following abstinence causes, among other symptoms, an intense craving for the abused drug, which in turn frequently results in the relapse into renewed drug use.
  • Epidemiological studies point to a high incidence of multiple substance abuse among cocaine users, a finding that has significant societal and medical repercussions.
  • the invention features methods for treating stimulant dependencies, such as cocaine craving, by administering a therapeutically- effective amount of a dopamine agonist, for example, pramipexole.
  • the invention provides a method of treating a patient (for example, a human) with a stimulant dependency by administering a therapeutically-effective amount of pramipexole to the patient.
  • a patient for example, a human
  • the stimulant dependency is a stimulant craving and the stimulant is cocaine.
  • the invention provides a method of treating a human diagnosed with cocaine craving by administering a therapeutically- effective amount of pramipexole to the human.
  • the method further includes administering a therapeutically- effective amount of an antidepressant or an anticonvulsant, for example, lamotrigine.
  • treating is meant the medical management of a patient with the intent that a cure, amelioration, or prevention of a dependency or a relapse or associated disease, pathological condition, or disorder will result.
  • This term includes active treatment, that is, treatment directed specifically toward improvement of the dependency or associated cure of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the dependency or associated disease, pathological condition, or disorder.
  • this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the dependency, disease, pathological condition, or disorder; preventive treatment, that is, treatment directed to prevention of the dependency or associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the dependency or associated disease, pathological condition, or disorder.
  • treating also includes symptomatic treatment, that is, treatment directed toward constitutional symptoms of the dependency or an associated disease, pathological condition, or disorder.
  • stimulant is meant any substance that temporarily increases functional activity, and preferably cardiac, respiratory, cerebral, nervous, vascular, motor, or vasomotor functional activity.
  • Preferred stimulants include, without limitation, cocaine, amphetamines, methamphetamine, and methylphenidate.
  • terapéuticaally-effective amount is meant an amount of a pramipexole compound sufficient to produce a healing, curative, or ameliorative effect either in the treatment of a stimulant dependency or in the symptoms of a stimulant dependency, for example, cocaine craving.
  • dependency is meant any form of behavior that indicates an altered or reduced ability to make decisions resulting, at least in part, from the use of stimulants. Representative forms of dependency behavior may take the form of antisocial, inappropriate, or illegal behavior and include those behaviors directed at the desire, planning, acquiring, and use of stimulants.
  • This term also includes the psychic craving for a drug that may or may not be accompanied by a physiological dependency, as well as a state in which there is a compulsion to take a drug, either continuously or periodically, in order to experience its psychic effects or to avoid the discomfort of its absence.
  • Dependency include habituation, that is, an emotional or psychological dependence on a compound to obtain relief from tension and emotional discomfort, as well as physical or physiological dependence, that is, use of a compound to prevent withdrawal symptoms.
  • craving is meant a behavior that reflects a consuming desire, longing, or yearning for a stimulant. This term may refer to aspects of behaviors that are components of a dependency.
  • the present invention provides a number of advantages. Importantly, it provides one of the first therapeutics for the treatment of stimulant cravings (such as cocaine craving).
  • stimulant cravings such as cocaine craving
  • the pramipexole utilized herein is non-toxic, is pharmocokinetically understood, and is known to be well tolerated by humans, as is evidenced by its approval for the treatment of Parkinson's Disease.
  • Figure 1 is a schematic illustration of the molecular structure of pramipexole, marketed as Mirapex in the United States.
  • the invention described herein features methods involving the administration of pramipexole (or other dopamine-D3/D2 agonists) for the treatment of stimulant dependency, and preferably for the treatment of cocaine craving and its symptoms, as well as cocaine dependency and associated self-destructive behaviors.
  • Mr. A a 34 year-old single, successful business man, was referred for evaluation of possible bipolar disorder.
  • Pramipexole is a non-ergot derivative which may be used at a range of between about 1.5 mg to 6.0 mg per day, and is preferably administered between about 1.5 mg and 4.5 mg per day. Higher dosages may be used with the concomitant risk of potential side effects.
  • formulations for treatment or prevention of stimulant dependency or craving such as cocaine craving, as described herein, may take the form of a dopamine agonist compound that may be combined with a pharmaceutically-acceptable diluent, carrier, stabilizer, or excipient.
  • Oral administration is preferred, but any other appropriate route of administration may be employed, for example, parenteral, intravenous, subcutaneous, intramuscular, intracranial, intraorbital, ophthalmic, intraventricular, intracapsular, intraspinal, intracisternal, intraperitoneal, intranasal, or aerosol administration.
  • Therapeutic formulations may be in the form of liquid solutions or suspensions (as, for example, for intravenous administration); for oral administration, formulations may be in the form of liquids, tablets or capsules; and for intranasal formulations, in the form of powders, nasal drops, or aerosols.
  • Formulations for parenteral administration may, for example, contain excipients, sterile water, saline, polyalkylene glycols such as polyethylene glycol, oils of vegetable origin, or hydrogenated napthalenes.
  • slow release or extended release delivery systems may be utilized.
  • Biocompatible, biodegradable lactide polymer, lactide/glycolide copolymer, or polyoxyethylene-polyoxypropylene copolymers may be used to control the release of the compounds.
  • Other potentially useful parenteral delivery systems include ethylene-vinyl acetate copolymer particles, osmotic pumps, implantable infusion systems, and liposomes.
  • Formulations for inhalation may contain excipients, for example, lactose, or may be aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or may be oily solutions for administration in the form of nasal drops, or as a gel.
  • a dopamine agonist for use in the methods of the invention is administered at a dosage appropriate to the effect to be achieved and is typically administered in unit dosage form.
  • the preferred route of administration for most indications is oral.
  • An effective quantity of a dopamine agonist-containing compound of the invention is employed to treat the stimulant dependency or craving, for example, cocaine craving as described herein.
  • the exact dosage of the compound may be dependent, for example, upon the age and weight of the recipient, the route of administration, and the severity and nature of the symptoms to be treated. In general, the dosage selected should be sufficient to prevent, ameliorate, or treat the condition, or one or more symptoms thereof, without producing significant toxic or undesirable side effects.
  • pramipexole is Pharmacia & Upjohn, Inc. which markets Mirapex (Pramipexole Dihydrochloride) tablets which have the molecular structure shown in Figure 1.
  • dopamine agonists include, but are not limited to, amantadine, bromocriptine, cabergoline, lisuride, pergolide, ropinirole, quinpirole, or quinelorane.
  • Pramipexole, or any other dopamine agonist may be administered as a monotherapy, or in combination with other compounds, for the treatment of multiple substance abuse or other physiological or psychological conditions.
  • the dopamine agonist e.g.
  • pramipexole may be administered in combination with an antidepressant, anticonvulsant, antianxiety, antimanic, antipyschotic, antiobsessional, sedative-hypnotic, or stimulant medication.
  • these medications include, but are not limited to, the antianxiety medications alprazolam, buspirone hydrochloride, chlordiazepoxide, chlordiazepoxide hydrochloride, clorazepate dipotassium, desipramine hydrochloride, diazepam, halazepam, hydroxyzine hydrochloride, hydroxyzine pamoate, lorazepam, meprobamate, oxazepam, prazepam, prochlorperazine maleate, prochlorperazine, prochlorperazine edisylate, and trimipramine maleate; the anticonvulsants amobarbital, amobarbital sodium, carbamazepine

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  • 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)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed herein are methods for reducing stimulant dependency or craving, involving administration of a therapeutically-effective amount of a dopamine agonist, such as pramipexole.

Description

USE OF PRAMIPEXOFF AS A TREATMENT FOR COCATNF,
CRAVTNG
Background of the Invention
This invention relates to methods for the treatment of cocaine craving.
Cocaine is a highly addictive pyschostimulant that causes sensations of euphoria and craving, resulting in physiological as well as psychological damage. Although cocaine use leads to a multitude of physiological complications, its primary target of action is the central nervous system. Cocaine withdrawal following abstinence causes, among other symptoms, an intense craving for the abused drug, which in turn frequently results in the relapse into renewed drug use. Epidemiological studies point to a high incidence of multiple substance abuse among cocaine users, a finding that has significant societal and medical repercussions.
To date, approved pharmacotherapies for cocaine abuse and dependence have proven scarce despite the acute need for such therapies.
Summary of the Invention
In general, the invention features methods for treating stimulant dependencies, such as cocaine craving, by administering a therapeutically- effective amount of a dopamine agonist, for example, pramipexole.
In one aspect, the invention provides a method of treating a patient (for example, a human) with a stimulant dependency by administering a therapeutically-effective amount of pramipexole to the patient. In preferred embodiments of this aspect, the stimulant dependency is a stimulant craving and the stimulant is cocaine.
In a related aspect, the invention provides a method of treating a human diagnosed with cocaine craving by administering a therapeutically- effective amount of pramipexole to the human.
In preferred embodiments of both of the above aspects of the invention, the method further includes administering a therapeutically- effective amount of an antidepressant or an anticonvulsant, for example, lamotrigine.
By "treating" is meant the medical management of a patient with the intent that a cure, amelioration, or prevention of a dependency or a relapse or associated disease, pathological condition, or disorder will result. This term includes active treatment, that is, treatment directed specifically toward improvement of the dependency or associated cure of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the dependency or associated disease, pathological condition, or disorder. In addition, this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the dependency, disease, pathological condition, or disorder; preventive treatment, that is, treatment directed to prevention of the dependency or associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the dependency or associated disease, pathological condition, or disorder. The term "treating" also includes symptomatic treatment, that is, treatment directed toward constitutional symptoms of the dependency or an associated disease, pathological condition, or disorder. By "stimulant" is meant any substance that temporarily increases functional activity, and preferably cardiac, respiratory, cerebral, nervous, vascular, motor, or vasomotor functional activity. Preferred stimulants include, without limitation, cocaine, amphetamines, methamphetamine, and methylphenidate.
By "therapeutically-effective amount" is meant an amount of a pramipexole compound sufficient to produce a healing, curative, or ameliorative effect either in the treatment of a stimulant dependency or in the symptoms of a stimulant dependency, for example, cocaine craving. By "dependency" is meant any form of behavior that indicates an altered or reduced ability to make decisions resulting, at least in part, from the use of stimulants. Representative forms of dependency behavior may take the form of antisocial, inappropriate, or illegal behavior and include those behaviors directed at the desire, planning, acquiring, and use of stimulants. This term also includes the psychic craving for a drug that may or may not be accompanied by a physiological dependency, as well as a state in which there is a compulsion to take a drug, either continuously or periodically, in order to experience its psychic effects or to avoid the discomfort of its absence. Forms of "dependency" include habituation, that is, an emotional or psychological dependence on a compound to obtain relief from tension and emotional discomfort, as well as physical or physiological dependence, that is, use of a compound to prevent withdrawal symptoms.
By "craving" is meant a behavior that reflects a consuming desire, longing, or yearning for a stimulant. This term may refer to aspects of behaviors that are components of a dependency.
The present invention provides a number of advantages. Importantly, it provides one of the first therapeutics for the treatment of stimulant cravings (such as cocaine craving). In addition, the pramipexole utilized herein is non-toxic, is pharmocokinetically understood, and is known to be well tolerated by humans, as is evidenced by its approval for the treatment of Parkinson's Disease.
Brief Description of the Drawings
Figure 1 is a schematic illustration of the molecular structure of pramipexole, marketed as Mirapex in the United States.
Detailed Description of the Invention The invention described herein features methods involving the administration of pramipexole (or other dopamine-D3/D2 agonists) for the treatment of stimulant dependency, and preferably for the treatment of cocaine craving and its symptoms, as well as cocaine dependency and associated self-destructive behaviors.
Described below is an example of the successful use of pramipexole for the treatment of cocaine craving and related symptoms. This example is provided for the purpose of illustrating the invention, and should not be construed as limiting.
Treatment of Cocaine Craving T Jsing Pramipexole
Mr. A, a 34 year-old single, successful business man, was referred for evaluation of possible bipolar disorder. Currently depressed, he had in the previous year brought financial ruin on himself by a pattern of cocaine freebasing and sexual and other extravagance that absorbed nearly one million dollars.
Along with current major depression, persisting cocaine craving but rare use, and a question of past primary or secondary (to substance abuse) mania, he manifested an extraordinary movement disorder with constant restlessness and thrashing of his legs, leaving the inner aspects of his knees and thighs bruised and discolored with hematomas in various stages of evolution and resolution. For the restless legs, he had consulted a neurologist who diagnosed
"pre-parkinsonism" presumed secondary to neurological damage from cocaine. The disfiguring movements limited his ability to return to and conduct business.
Previously, he had failed to respond to or tolerate most of the new generation of antidepressants. Treatment was begun with lamotrigine up to 200 mg with modest improvement in mood. Given his severe restless legs syndrome and persisting depression, pramipexole was added, titrated to 1.5 mg a day in divided doses.
In response to this treatment, his leg movements quieted substantially, his mood brightened, and he reported that these were the first days in a year that he awoke without craving cocaine, a benefit sustained for one year on this drug, combined with 75 mg of lamotrigine. During the subsequent year, Mr. A. reported one day of non-compliance when he was out of town without his medication. That night, for the first time, he dreamt about cocaine and the next day experienced a renewed craving on awakening which resolved when treatment was restored.
Although he faces an array of financial and business challenges, his mood following treatment is nearly euthymic, his leg movements at worst resemble mild restlessness, and his cocaine craving remains abolished. These dramatic results demonstrate that dopamine agonists, like pramipexole, represent treatments for cocaine craving, and may be particularly useful for patients with comorbid refractory depression. Pramipexole and Other Dopamine Agonists
The synthesis of pramipexole is described in U.S. Patent No.
4,886,812 and European Patent 186 087. Pramipexole is a non-ergot derivative which may be used at a range of between about 1.5 mg to 6.0 mg per day, and is preferably administered between about 1.5 mg and 4.5 mg per day. Higher dosages may be used with the concomitant risk of potential side effects.
Other formulations for treatment or prevention of stimulant dependency or craving, such as cocaine craving, as described herein, may take the form of a dopamine agonist compound that may be combined with a pharmaceutically-acceptable diluent, carrier, stabilizer, or excipient.
Conventional pharmaceutical practice is employed to provide suitable formulations or compositions to administer such compositions to patients.
Oral administration is preferred, but any other appropriate route of administration may be employed, for example, parenteral, intravenous, subcutaneous, intramuscular, intracranial, intraorbital, ophthalmic, intraventricular, intracapsular, intraspinal, intracisternal, intraperitoneal, intranasal, or aerosol administration. Therapeutic formulations may be in the form of liquid solutions or suspensions (as, for example, for intravenous administration); for oral administration, formulations may be in the form of liquids, tablets or capsules; and for intranasal formulations, in the form of powders, nasal drops, or aerosols.
Methods well known in the art for making formulations are described, for example, in "Remington: The Science and Practice of Pharmacy" (19th ed.) ed. A.R. Gennaro AR., 1995, Mack Publishing
Company, Easton, PA. Formulations for parenteral administration may, for example, contain excipients, sterile water, saline, polyalkylene glycols such as polyethylene glycol, oils of vegetable origin, or hydrogenated napthalenes.
If desired, slow release or extended release delivery systems may be utilized. Biocompatible, biodegradable lactide polymer, lactide/glycolide copolymer, or polyoxyethylene-polyoxypropylene copolymers may be used to control the release of the compounds. Other potentially useful parenteral delivery systems include ethylene-vinyl acetate copolymer particles, osmotic pumps, implantable infusion systems, and liposomes. Formulations for inhalation may contain excipients, for example, lactose, or may be aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or may be oily solutions for administration in the form of nasal drops, or as a gel.
In general, a dopamine agonist for use in the methods of the invention is administered at a dosage appropriate to the effect to be achieved and is typically administered in unit dosage form. As noted above, the preferred route of administration for most indications is oral.
An effective quantity of a dopamine agonist-containing compound of the invention is employed to treat the stimulant dependency or craving, for example, cocaine craving as described herein. The exact dosage of the compound may be dependent, for example, upon the age and weight of the recipient, the route of administration, and the severity and nature of the symptoms to be treated. In general, the dosage selected should be sufficient to prevent, ameliorate, or treat the condition, or one or more symptoms thereof, without producing significant toxic or undesirable side effects. Combination with Other Therapeutics
One particular source of pramipexole is Pharmacia & Upjohn, Inc. which markets Mirapex (Pramipexole Dihydrochloride) tablets which have the molecular structure shown in Figure 1. Examples of other dopamine agonists include, but are not limited to, amantadine, bromocriptine, cabergoline, lisuride, pergolide, ropinirole, quinpirole, or quinelorane. Pramipexole, or any other dopamine agonist, may be administered as a monotherapy, or in combination with other compounds, for the treatment of multiple substance abuse or other physiological or psychological conditions. In one particular example, the dopamine agonist (e.g. pramipexole) may be administered in combination with an antidepressant, anticonvulsant, antianxiety, antimanic, antipyschotic, antiobsessional, sedative-hypnotic, or stimulant medication. Examples of these medications include, but are not limited to, the antianxiety medications alprazolam, buspirone hydrochloride, chlordiazepoxide, chlordiazepoxide hydrochloride, clorazepate dipotassium, desipramine hydrochloride, diazepam, halazepam, hydroxyzine hydrochloride, hydroxyzine pamoate, lorazepam, meprobamate, oxazepam, prazepam, prochlorperazine maleate, prochlorperazine, prochlorperazine edisylate, and trimipramine maleate; the anticonvulsants amobarbital, amobarbital sodium, carbamazepine, chlordiazepoxide, chlordiazepoxide hydrochloride, clorazepate dipotassium, diazepam, divalproex sodium, ethosuximide, ethotoin, gabapentin, lamotrigine, magnesium sulfate, mephenytoin, mephobarbital, methsuximide, paramethadione, pentobarbital sodium, phenacemide, phenobarbital, phenobarbital sodium, phensuximide, phenytoin, phenytoin sodium, primidone, secobarbital sodium, trimethadione, valproic acid, and clonazepam; the antidepressants amitriptyline hydrochloride, amoxapine, bupropion hydrochloride, clomipramine hydrochloride, desipramine hydrochloride, doxepin hydrochloride, fluoxetine, fluvoxamine, imipramine hydrochloride, imipramine pamoate, isocarboxazid, lamotrigine, maprotoline hydrochloride, nortriptyline hydrochloride, paroxetine hydrochloride, phenelzine sulfate, protriptyline hydrochloride, sertraline hydrochloride, tranylcypromine sulfate, trazodone hydrochloride, trimipramine maleate, and venlafaxine hydrochloride; the antimanic medications lithium carbonate and lithium citrate; the antiobsessional medications fluvoxamine, and clomipramine hydrochloride; the antipsychotic medications acetophenazine maleate, chlorpromazine hydrochloride, chlorprothixene, chlorprothixene hydrochloride, clozapine, fluphenazine decanoate, fluphenazine enathrate, fluphenazine hydrochloride, haloperidol decanoate, haloperidol, haloperidol lactate, lithium carbonate, lithium citrate, loxapine hydrochloride, loxapine succinate, mesoridazine besylate, molindone hydrochloride, perphenazine, pimozide, prochlorperazine maleate, prochlorperazine, prochlorperazine edisylate, promazine hydrochloride, risperidone, thioridazine, thioridazine hydrochloride, thiothixene, thiothixene hydrochloride, and trifluoperzine hydrochloride; the sedative-hypnotic medications amobarbital, amobarbital sodium, aprobarbital, butabarbital, chloral hydrate, chlordiazepoxide, chlordiazepoxide hydrochloride, clorazepate dipotassium, diazepam, diphenhydramine, estazolam, ethchlorvynol, flurazepam hydrochloride, glutethimide, hydroxyzine hydrochloride, hydroxyzine pamoate, lorazepam, methotrimeprazine hydrochloride, midazolam hydrochloride, non prescription, oxazepam, pentobarbital sodium, phenobarbital, phenobarbital sodium, quazepam, secobarbital sodium, temazepam, triazolam, and zolpidem tartrate; and the stimulants dextroamphetamine sulfate, methamphetamine hydrochloride, methylphenidate hydrochloride and, pemoline. Other Embodiments
All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each independent publication or patent application was specifically and individually indicated to be incorporated by reference.
While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure that come within known or customary practice within the art to which the invention pertains and may be applied to the essential features hereinbefore set forth, and follows in the scope of the appended claims.
Other embodiments are within the claims. What is claimed is:

Claims

Claims
1. A method of treating a human with a stimulant dependency, said method comprising administering to said human a therapeutically-effective amount of pramipexole.
2. The method of claim 1, wherein said stimulant dependency involves a stimulant craving.
3. The method of claim 1, wherein said stimulant is cocaine.
4. A method of treating a cocaine craving in a human, said method comprising administering to said human a therapeutically-effective amount of pramipexole.
5. The method of claim 1 or 4, wherein said method further comprises administering to said human a therapeutically-effective amount of an antidepressant.
6. The method of claim 1 or 4, wherein said method further comprises administering to said human a therapeutically-effective amount of an anticonvulsant.
7. The method of claim 6, wherein the anticonvulsant is lamotrigine.
PCT/US2000/026634 1999-09-30 2000-09-28 Use of pramipexole as a treatment for cocaine craving WO2001022820A1 (en)

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AU76206/00A AU7620600A (en) 1999-09-30 2000-09-28 Use of pramipexole as a treatment for cocaine craving
CA002384840A CA2384840A1 (en) 1999-09-30 2000-09-28 Use of pramipexole as a treatment for cocaine craving
US10/088,628 US6750235B1 (en) 1999-09-30 2000-09-28 Pramipexole as a treatment for cocaine craving

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WO2001062249A1 (en) * 2000-02-23 2001-08-30 Pharmacia & Upjohn Company Use of pramipexole for the treatment of addictive disorders
WO2004010998A1 (en) * 2002-07-25 2004-02-05 Pharmacia Corporation Sustained-release tablet comprising reboxetine
WO2004010999A1 (en) * 2002-07-25 2004-02-05 Pharmacia Corporation Pramipexole once-daily dosage form
WO2004060297A2 (en) * 2002-12-31 2004-07-22 Medtronic Minimed, Inc. Hydrophilic cross-linking agents for use in enzymatic sensors
US7157480B2 (en) 2001-12-11 2007-01-02 University Of Virginia Patent Foundation Use of pramipexole to treat amyotrophic lateral sclerosis
US7695734B2 (en) 2004-08-13 2010-04-13 Boehringer Ingelheim International Gmbh Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof
US8399016B2 (en) 2002-07-25 2013-03-19 Boehringer Ingelheim International Gmbh Sustained-release tablet composition of pramipexole
US8445474B2 (en) 2006-05-16 2013-05-21 Knopp Neurosciences, Inc. Compositions of R(+) and S(−) pramipexole and methods of using the same
US8518926B2 (en) 2006-04-10 2013-08-27 Knopp Neurosciences, Inc. Compositions and methods of using (R)-pramipexole
US8524695B2 (en) 2006-12-14 2013-09-03 Knopp Neurosciences, Inc. Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same
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