WO2010025251A2 - Substances et procédés pour moduler l'appétit, le gain pondéral et le tdah en utilisant de la varénicline - Google Patents

Substances et procédés pour moduler l'appétit, le gain pondéral et le tdah en utilisant de la varénicline Download PDF

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WO2010025251A2
WO2010025251A2 PCT/US2009/055196 US2009055196W WO2010025251A2 WO 2010025251 A2 WO2010025251 A2 WO 2010025251A2 US 2009055196 W US2009055196 W US 2009055196W WO 2010025251 A2 WO2010025251 A2 WO 2010025251A2
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person
varenicline
animal
attention
analog
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WO2010025251A3 (fr
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Mark S. Gold
James Cocores
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University Of Florida Research Foundation, Inc.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
    • 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
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2063—Proteins, e.g. gelatin

Definitions

  • Nicotine is possibly one of the most prevalent dependence-producing drugs because of the central nicotinic-cholinergic, dopaminergic, serotonergic, and gabaminergic pathways with which it has been associated (Rosecrans, 1991). Nicotine dependent behavior conceivably may be reinforced by the drug's focus and memory enhancing (Levin and Rezvani, 2002), antidepressant (Di Matteo et al. , 2007), anxiolytic (Booker et al, 2007), and appetite suppressing properties (Chen el al, 2007). Nicotine is a unique paradigm in that it suppresses appetite and stabilizes mood. Nicotine withdrawal leads to the emergence of craving in dependent individuals, which can include impaired memory (Mendrek et al, 2006) and concentration, depressed mood, anxiety, and increased appetite (West et al, 2006).
  • Nicotine dependence is perpetuated by biobehavioral rewards generated as the result of nicotine's interaction with the brain's neurochemical systems (Rosecrans, 1991 ). Nicotine's memory-enhancing reward is believed to result from its effects on specific nicotinic acetylcholine receptors (Mansvelder et al, 2006). Nicotine's attentional, antidepressant, and antianxiety rewards are thought to be due to pathways between nicotinic acetylcholine receptors and noncholinergic neuronal subtypes that selectively traffic dopamine, norepinephrine, 5-hydroxytryptamine, and gamma-amino-butyric acid (Rosecrans et al, 1978).
  • Varenicline (CHANTIX, Pfizer, Missouri, KS) is a new treatment for nicotine dependence and a member of the selective alpha4beta2 nicotinic acetylcholine receptor partial agonist class (Lam and Patel, 2007; U.S. Patent Nos. 6,410,550; 6,890,927; and 7,265,1 19).
  • Central nicotinic acetylcholine receptors have been implicated in attention deficit hyperactivity disorder (ADHD) (Potter et a , 2006), and an alpha4beta2 antagonist counteracted nicotine-induced improvement in an animal model of ADHD (Ueno et a , 2002).
  • ADHD attention deficit hyperactivity disorder
  • the present invention concerns methods and materials for modulating appetite and weight reduction in persons or animals.
  • an effective amount of a compound of varenicline or a composition comprising the drug varenicline, or a pharmaceutically acceptable salt and/or analog thereof is administered to a person or animal in need of appetite inhibition or suppression and weight reduction.
  • the present invention also concerns methods and materials for treating ADHD in persons or animals.
  • an effective amount of a compound of varenicline or a composition comprising the drug varenicline, or a pharmaceutically acceptable salt and/or analog thereof is administered to a person or animal in need of treatment for a hyperactivity or attention-deficit disorder.
  • the person or animal is one that has been clinically diagnosed as having ADHD.
  • the subject invention also concerns compositions comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof, and one or more compounds that suppress or inhibit appetite and/or promote weight reduction in a person or animal.
  • the subject invention also concerns compositions comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof, and one or more compounds used to treat hyperactivity and/or attention-deficit disorders in a person or animal.
  • the present invention concerns methods and materials for modulating appetite and/or weight reduction in persons or animals.
  • an effective amount of a compound of varenicline or a composition comprising the drug varenicline, or a pharmaceutically acceptable salt and/or analog thereof is administered to a person or animal in need of appetite inhibition or suppression and weight reduction.
  • the person or animal is one that has been diagnosed as overweight.
  • the person or animal is one that has been diagnosed as clinically obese.
  • the person can be a smoker or non-smoker. It is contemplated that if the person is a non-smoker, then the dosage of varenicline to be administered will be less than if the person is a smoker.
  • the person or animal is also treated with or is already being treated with one or more other appetite suppression and/or weight reduction drugs.
  • the other drug is orlistat, sibutramine, mazindol, xenical, rimonabant or diethylpropion, or an isomer or analog thereof.
  • Methods of the invention can also optionally comprise implementing a caloric reduction regimen, and/or exercise, and/or bariatric surgery, and/or any other therapy for suppressing appetite and/or reducing weight of a person or animal.
  • the present invention also concerns methods and materials for treating a hyperactivity and/or attention-deficit disorder, such as attention-deficit disorder (ADD) and ADHD, and/or a memory disorder in persons or animals.
  • a hyperactivity and/or attention-deficit disorder such as attention-deficit disorder (ADD) and ADHD
  • a memory disorder in persons or animals.
  • an effective amount of a compound of varenicline or a composition comprising the drug varenicline, or a pharmaceutically acceptable salt and/or analog thereof is administered to a person or animal in need of treatment for a hyperactivity or attention-deficit or memory disorder.
  • the person or animal is one that has been clinically diagnosed as having an attention-deficit disorder, such as ADHD.
  • the person can be a smoker or non-smoker.
  • the dosage of varenicline to be administered will be less than if the person is a smoker.
  • the person or animal is being treated with one or more other drags for the treatment of a hyperactivity and/or attention-deficit disorder.
  • the other drug is methylphenidate, atomoxetine, buproprion, an alpha-2 agonist (e.g. CLONIDINE), dexmethylphenidate, amphetamine, lisdexamfetamine, or dextroamphetamine, or an isomer or analog thereof.
  • Methods of the invention can also optionally comprise implementing other therapy for the treatment of a hyperactivity and/or attention-deficit disorder in a person or animal.
  • the subject invention also concerns compositions comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof, and one or more compounds that suppress or inhibit appetite and/or promote weight reduction in a person or animal.
  • the subject invention also concerns compositions comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof, and one or more compounds used to treat hyperactivity and/or attention-deficit disorders in a person or animal.
  • the compound varenicline can be administered as an isolated compound in the methods of the invention, this compound can also be administered as part of a pharmaceutical composition.
  • the subject invention thus further provides compositions comprising one or more compounds or agents in association with at least one pharmaceutically acceptable carrier, diluent and/or adjuvant.
  • the pharmaceutical composition can be adapted for various routes of administration, such as enteral, parenteral, intravenous, intramuscular, topical, subcutaneous, and so forth. Administration can be continuous or at distinct intervals, as can be determined by a person of ordinary skill in the art.
  • the compounds of the invention can be formulated according to known methods for preparing pharmaceutically useful compositions.
  • Formulations are described in a number of sources which are well known and readily available to those skilled in the art.
  • Remington 's Pharmaceutical Science (Martin 1995) describes formulations which can be used in connection with the subject invention.
  • Formulations suitable for administration include, for example, aqueous sterile injection solutions, which may contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient; and aqueous and nonaqueous sterile suspensions which may include suspending agents and thickening agents.
  • compositions of the subject invention can include other agents conventional in the art having regard to the type of formulation in question.
  • the compounds of the present invention include all hydrates and salts that can be prepared by those of skill in the art.
  • compositions of the present invention are sufficiently basic or acidic to form stable nontoxic acid or base salts
  • administration of the compounds as salts may be appropriate.
  • pharmaceutically acceptable salts are organic acid addition salts formed with acids that form a physiological acceptable anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, alpha-ketoglutarate, and alpha- glycerophosphate.
  • Suitable inorganic salts may also be formed, including hydrochloride, sulfate, nitrate, bicarbonate, and carbonate salts.
  • salts of a compound may be obtained using standard procedures well known in the art, for example, by reacting a sufficiently basic compound such as an amine with a suitable acid affording a physiologically acceptable anion.
  • a sufficiently basic compound such as an amine
  • a suitable acid affording a physiologically acceptable anion.
  • Alkali metal (for example, sodium, potassium or lithium) or alkaline earth metal (for example calcium) salts of carboxylic acids can also be made.
  • Compounds of the invention, and compositions thereof may be systemically administered, such as intravenously or orally, optionally in combination with a pharmaceutically acceptable carrier such as an inert diluent, or an assimilable edible carrier for oral delivery. They may be enclosed in hard or soft shell gelatin capsules, may be compressed into tablets, or may be incorporated directly with the food of the patient's diet.
  • a pharmaceutically acceptable carrier such as an inert diluent, or an assimilable edible carrier for oral delivery. They may be enclosed in hard or soft shell gelatin capsules, may be compressed into tablets, or may be incorporated directly with the food of the patient's diet.
  • the active compound may be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, aerosol sprays, chewing gums, and the like.
  • the tablets, troches, pills, capsules, and the like may also contain the following: binders such as gum tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and/or a sweetening agent such as sucrose, fructose, lactose or aspartame or a flavoring agent such as peppermint, oil of wintergreen, or cherry flavoring may be added.
  • a liquid carrier such as a vegetable oil or a polyethylene glycol.
  • any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed.
  • the active compound may be incorporated into sustained-release preparations and devices.
  • compositions of the invention can be administered intravenously, intramuscularly, or intraperitoneally by infusion or injection.
  • Solutions of the active agent or its salts can be prepared in water, optionally mixed with a nontoxic surfactant.
  • Dispersions can also be prepared in glycerol, liquid polyethylene glycols, triacetin, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations can contain a preservative to prevent the growth of microorganisms.
  • the pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions, optionally encapsulated in liposomes.
  • the ultimate dosage form should be sterile, fluid and stable under the conditions of manufacture and storage.
  • the liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising, for example, water, ethanol, a polyol (for example, glycerol, propylene glycol, liquid polyethylene glycols, and the like), vegetable oils, nontoxic glyceryl esters, and suitable mixtures thereof.
  • the proper fluidity can be maintained, for example, by the formation of liposomes, by the maintenance of the required particle size in the case of dispersions or by the use of surfactants.
  • the prevention of the action of microorganisms can be brought about by various other antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like.
  • isotonic agents for example, sugars, buffers or sodium chloride.
  • Prolonged absorption of the injectable compositions can be brought about by the inclusion of agents that delay absorption, for example, aluminum monostearate and gelatin.
  • Sterile injectable solutions are prepared by incorporating a compound of the invention in the required amount in the appropriate solvent with various other ingredients enumerated above, as required, followed by filter sterilization.
  • the preferred methods of preparation are vacuum drying and the freeze drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile-filtered solutions.
  • compositions of the invention can comprise between about 0.1% and 45%, and especially, 1 and 15%, by weight of the total of one or more of the compounds based on the weight of the total composition including carrier or diluents.
  • dosage levels of the administered active ingredients can be: intravenous, 0.01 to about 20 mg/kg; intraperitoneal, 0.01 to about 100 mg/kg; subcutaneous, 0.01 to about 100 mg/kg; intramuscular, 0.01 to about 100 mg/kg; orally 0.01 to about 200 mg/kg, and preferably about 1 to 100 mg/kg; intranasal instillation, 0.01 to about 20 mg/kg; and aerosol, 0.01 to about 20 mg/kg of animal (body) weight.
  • about 0.25 mg to 2.0 mg of varenicline is administered one or two times a day to a person or animal.
  • varenicline is administered one or two times a day to the person or animal.
  • 1.0 mg of varenicline is administered to the person or animal one or two times a day.
  • kits comprising in one or more containers: varenicline or a composition comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof, and optionally one or more compounds that suppress or inhibit appetite and/or promote weight reduction and/or one or more compounds used to treat hyperactivity and/or attention-deficit disorders.
  • a kit comprises one or more of methylphenidate, atomoxetine, or dextroamphetamine, or an isomer or analog thereof.
  • a kit comprises one or more of orlistat, sibutramine, mazindol, or diethylpropion, or an isomer or analog thereof.
  • Kits of the invention can optionally include pharmaceutically acceptable carriers and/or diluents.
  • a kit of the invention includes one or more other components, adjuncts, or adjuvants as described herein.
  • a kit of the invention includes instructions or packaging materials that describe how to administer and/or how to use a compound or composition of the kit for the suppression or inhibition of appetite and/or promotion of weight reduction and/or for the treatment of hyperactivity and/or an attention-deficit disorder.
  • Containers of the kit can be of any suitable material, e.g., glass, plastic, metal, etc., and of any suitable size, shape, or configuration.
  • a compound of the invention is provided in the kit as a solid, such as a tablet, pill, chewing gum, or powder form.
  • a compound of the invention is provided in the kit as a liquid or solution.
  • the kit comprises an ampoule or syringe containing a compound of the invention in liquid or solution form.
  • Mammalian species which benefit from the disclosed methods include, but are not limited to, primates, such as apes, chimpanzees, orangutans, humans, monkeys; domesticated animals ⁇ e.g., pets) such as dogs, cats, guinea pigs, hamsters, Vietnamese pot-bellied pigs, rabbits, and ferrets; domesticated farm animals such as cows, buffalo, bison, horses, donkey, swine, sheep, and goats; exotic animals typically found in zoos, such as bear, lions, tigers, panthers, elephants, hippopotamus, rhinoceros, giraffes, antelopes, sloth, gazelles, zebras, wildebeests, prairie dogs, koala bears, kangaroo, opossums, raccoons, pandas, hyena, seals, sea lions, elephant seals, otters, porpoises
  • Duloxetine 30 mg was started for depression and pain management, and gabapentin 900 mg for alcohol detoxification and craving reduction, as an anxiolytic and mood stabilizer, and for pain. Gabapentin was raised eventually to 1600 mg daily and her level of functioning improved in the face of enormous stress associated with her disabled son, and ex -husband. She relapsed in February 2007 by having a drink of vodka every few days.
  • Ms. A. was prescribed varenicline 1 mg twice daily, and was instructed to eat a low-acid meal with an eight-ounce glassful of water before taking the medicine, as a means of curtailing her drinking.
  • varenicline works like nicotine to suppress appetite, cause weight loss, and stabilize cognition and mood.
  • This case report does suggest that the new selective alpha4beta2 nicotinic-choline receptor partial agonist is a new and perhaps more promising clinical psychopharmacologic prototype for appetite suppression and weight reduction because, unlike many other diet pills, varenicline may improve cognition and mood rather than causing disturbances that require discontinuation.
  • the appctitc/obesity-varenicline interface warrants further investigation, using larger groups of subjects and more sophisticated study design, not only as a novel treatment but also to help unravel the unsolved neuropsychiatric puzzle behind the brain disease commonly known as obesity.
  • Example 2 Case Report Regarding ADHD Ms.
  • A a 26-year-old white female, was self-referred in February 2007 for difficulties staying focused, on task, and with reading comprehension. She fulfilled DSM-IV-TR criteria for ADHD, but was adamantly against the initial recommendation to begin taking a prescription stimulant.
  • Medicine selected was based on office sample availability at Ms. A's request because of financial problems. A wealthier patient had previously donated a barely-used varenicline prescription that she had abandoned due to nausea. Ms.
  • varenicline-ADHD interface warrants further investigation using larger groups of subjects, more sophisticated study designs, and a variety of memory deficits such as depression and mild cognitive impairment.
  • Example 3 Dose The approved dose is 1 mg of Varenicline bid.
  • One dose one to two hours before dinner and the other before lunch with a healthy snack such as fruit, low sodium vegetable juice or apple sauce.
  • the dose form for weight reduction or ADHD would be 1/16 to 1 A bid of the approved dose delivered in a healthy drink or apple sauce at breakfast and after school for pediatric populations.
  • Formulation The standard formulation prepared by Pfizer are pills in .5 (available only during the first 7 days of treatment) and 1.0 mg dosages.

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Abstract

La présente invention concerne des procédés et des matériaux pour moduler l'appétit et la réduction pondérale chez des personnes et des animaux. La présente invention concerne également des procédés et des substances pour traiter l'hyperactivité et les troubles de déficit de l'attention, comme le TDAH, chez des personnes ou des animaux. L'invention sujet concerne également des compositions contenant de la varénicline, ou l'un de ses sels et/ou analogues pharmaceutiquement acceptables, et un ou plusieurs composés qui suppriment ou inhibent l'appétit et/ou favorisent la réduction pondérale chez une personne ou un animal. L'invention sujet concerne également des compositions comprenant de la varénicline ou l'un de ses sels et/ou analogues pharmaceutiquement acceptables, et un ou plusieurs composés utilisés pour traiter l'hyperactivité et les troubles de déficit de l'attention chez une personne ou un animal.
PCT/US2009/055196 2008-08-27 2009-08-27 Substances et procédés pour moduler l'appétit, le gain pondéral et le tdah en utilisant de la varénicline WO2010025251A2 (fr)

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US61/092,224 2008-08-27

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WO2010025251A3 WO2010025251A3 (fr) 2010-06-10

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012101060A1 (fr) * 2011-01-27 2012-08-02 Novartis Ag Utilisation d'activateurs du récepteur nicotinique de l'acétylcholine alpha 7
WO2014058742A1 (fr) * 2012-10-09 2014-04-17 Sears Douglas Traitement thérapeutique

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006049941A2 (fr) * 2004-10-27 2006-05-11 Neurogen Corporation Diaryl urees, antagonistes du cb1
US20070078135A1 (en) * 2005-04-18 2007-04-05 Neurogen Corporation Substituted heteroaryl CB1 antagonists
US20080009477A1 (en) * 2004-11-04 2008-01-10 Neurogen Corporation Arylalkyl Ureas As Cb1 Antagonists

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006049941A2 (fr) * 2004-10-27 2006-05-11 Neurogen Corporation Diaryl urees, antagonistes du cb1
US20080009477A1 (en) * 2004-11-04 2008-01-10 Neurogen Corporation Arylalkyl Ureas As Cb1 Antagonists
US20070078135A1 (en) * 2005-04-18 2007-04-05 Neurogen Corporation Substituted heteroaryl CB1 antagonists

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012101060A1 (fr) * 2011-01-27 2012-08-02 Novartis Ag Utilisation d'activateurs du récepteur nicotinique de l'acétylcholine alpha 7
CN103442701A (zh) * 2011-01-27 2013-12-11 诺瓦提斯公司 烟碱乙酰胆碱受体α7激活剂的用途
WO2014058742A1 (fr) * 2012-10-09 2014-04-17 Sears Douglas Traitement thérapeutique
US10682409B2 (en) 2012-10-09 2020-06-16 Attentive Therapeutics, Inc. Therapeutic treatment

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