WO2010025251A2

WO2010025251A2 - Materials and methods for modulating appetite, weight gain and adhd using varenicline

Info

Publication number: WO2010025251A2
Application number: PCT/US2009/055196
Authority: WO
Inventors: Mark S. Gold; James Cocores
Original assignee: University Of Florida Research Foundation, Inc.
Priority date: 2008-08-27
Filing date: 2009-08-27
Publication date: 2010-03-04
Also published as: WO2010025251A3

Abstract

The present invention concerns methods and materials for modulating appetite and weight reduction in persons or animals. The present invention also concerns methods and materials for treating, hyperactivity and attention-deficit disorders, such as ADHD in persons or animals. 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.

Description

DESCRIPTION

MATERIALS AND METHODS FOR MODULATING APPETITE, WEIGHT GAIN AND ADHD USING VARENICLINE

CROSS-REFERENCE TO RELATED APPLICATION

The present application claims the benefit of U.S. Provisional Application Serial No. 61/092,224, filed August 27, 2008, which is hereby incorporated by reference herein in its entirety, including any figures, tables, nucleic acid sequences, amino acid sequences, and drawings.

BACKGROUND OF THE INVENTION

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). Although less clearly understood than nicotine withdrawal, food-seeking behavior also is believed to involve an array of neuropsychiatric reward pathways: nicotinic- cholinergic (Maier et ah, 2004), dopaminergic (Wise, 2006), serotonergic, and GAB Anergic (Dimitropoulos el ah, 2000) reward systems are among the likely candidates that motivate us to eat. Food seeking has been associated with depression, stress, and emotional discomfort (Gibson, 2006), and food tasting alone can stabilize mood (Yamamoto, 2006).

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).

BRIEF SUMMARY OF THE INVENTION

The present invention concerns methods and materials for modulating appetite and weight reduction in persons or animals. In one embodiment, 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. In one embodiment, 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. In a specific embodiment, 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.

DETAILED DESCRIPTION OF THE INVENTION The present invention concerns methods and materials for modulating appetite and/or weight reduction in persons or animals. In one embodiment, 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. In a specific embodiment, the person or animal is one that has been diagnosed as overweight. In another embodiment, 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. In one embodiment, 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. In one embodiment, 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. In one embodiment, 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. In a specific embodiment, 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. 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. In one embodiment, the person or animal is being treated with one or more other drags for the treatment of a hyperactivity and/or attention-deficit disorder. In one embodiment, 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.

While 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. In one embodiment, 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. For example, 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. The formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze dried (lyophilized) condition requiring only the condition of the sterile liquid carrier, for example, water for injections, prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powder, granules, tablets, etc. It should be understood that in addition to the ingredients particularly mentioned above, the 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. Under conditions where the compounds 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. Examples of 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.

Pharmaceutically acceptable 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. Alkali metal (for example, sodium, potassium or lithium) or alkaline earth metal (for example calcium) salts of carboxylic acids can also be made.

Therapeutic application of compounds and compositions containing them can be accomplished by any suitable therapeutic method and technique presently or prospectively known to those skilled in the art. 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. For oral therapeutic administration, 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. When the unit dosage form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier, such as a vegetable oil or a polyethylene glycol. Various other materials may be present as coatings or to otherwise modify the physical form of the solid unit dosage form. For instance, tablets, pills, or capsules may be coated with gelatin, wax, shellac, or sugar and the like. A syrup or elixir may contain the active compound, sucrose or fructose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor. Of course, any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. In addition, the active compound may be incorporated into sustained-release preparations and devices.

Compounds and compositions of the invention, including pharmaceutically acceptable salts or analogs thereof, 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. Optionally, 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. In many cases, it will be preferable to include 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. In the case of sterile powders for the preparation of sterile injectable solutions, 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.

To provide for the administration of dosages for the desired therapeutic treatment, in some embodiments, pharmaceutical 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. Illustratively, 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. In a specific embodiment, about 0.25 mg to 2.0 mg of varenicline is administered one or two times a day to a person or animal. In a more specific embodiment, 0.5 mg to 1.5 mg of varenicline is administered one or two times a day to the person or animal. In an exemplified embodiment, 1.0 mg of varenicline is administered to the person or animal one or two times a day.

The subject invention also concerns 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. In one embodiment, a kit comprises one or more of methylphenidate, atomoxetine, or dextroamphetamine, or an isomer or analog thereof. In another embodiment, 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. In one embodiment, a kit of the invention includes one or more other components, adjuncts, or adjuvants as described herein. In one embodiment, 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. In one embodiment, a compound of the invention is provided in the kit as a solid, such as a tablet, pill, chewing gum, or powder form. In another embodiment, a compound of the invention is provided in the kit as a liquid or solution. In one embodiment, 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, dolphins, and whales. Other species that may benefit from the disclosed methods include fish, amphibians, avians, and reptiles. As used herein, the terms "patient" and "subject" are used interchangeably and are intended to include such human and non-human species.

Following are examples that illustrate procedures for practicing the invention. These examples should not be construed as limiting. All percentages are by weight and all solvent mixture proportions are by volume unless otherwise noted. Example 1 — Case Report Regarding Weight Reduction

Ms, A., a 66-year-old white woman, was referred by another patient in November 2006 for alcohol, depression, anxiety, panic, and chronic pain from pedal peripheral neuropathy of unknown etiology. Ms. A. met DSM-IV-TR criteria for alcohol dependence, and cyclothymic disorder. 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. She was adamantly opposed to Alcoholics Anonymous and residential alcohol detoxification and rehabilitation programs. She stopped drinking by mid-March and remained abstinent for about three months. Then, according to Ms. A., overwhelming amounts of stress led her to slip, and by the beginning of July she was consuming six to eight drinks daily. 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. She returned a week later, with the same magnitude of problems, and proudly reported she had lost five pounds (down to 160, 5-foot-3, BMI = 28); had stopped drinking alcohol; had regained her energy, ambition, focus, memory, and more pleasant mood; no longer had transient facial tics; and had noticeably less tension in her face. The only persistent side effect was mild nausea, which was ever-present but did not discourage her from continuing with the varenicline. A week later, she had lost an additional three pounds, still was not drinking, and was enjoying newly-reacquired cognitive and behavioral benefits. Ms. A. lost two pounds by the end of the third week, brought her BMI down to 27.

Comment

Though minimal, the placebo effect cannot be ruled out, nor can the possibility of a synergistic therapeutic benefit among the three medicines. Another possibility is that 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. The administration of the antidepressants bupropion (150 mg) and venlafaxine (up to 150 mg), each alone or in combination with valproic acid, were met with either side effects or undesirable results. 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. A agreed to undergo a trial of varenicline taking 0.5 mg in the morning, after eating a low-acid breakfast with a an 8-ounce glass of water. Her reading comprehension and ability to focus improved substantially after reaching 1 mg twice daily. Her mild hyperactivity improved marginally. She complained of no side effects as she completed 6 weeks, including weekends, of the clinic's subsidized varenicline treatment trial. Her problematic ADHD symptoms fully re-surfaced about two days after she ran out of varenicline. Ms. A agreed to continue medicine trials using affordable antidepressant, dopamine agonist, or nicotine replacement generics.

Comment

Although this report does not rule out the placebo effect, and a therapeutic connection between varenicline and ADHD can not be established with certainty, this case does suggest that the new selective alpha4beta2 nicotinic acetylcholine receptor partial agonist class of medicines is useful in the management of adult ADHD. In particular, the 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. Adults: >18 yrs: Days 1-3: 0.5mg qd (once a day). Days 4-7: 0.5mg bid (twice a day). Day 8 to End of Treatment: lmg bid. Duration: 12 weeks with additional 12 weeks after successful completion to ensure long-term abstinence. Severe Renal Impairment: Initial: 0.5mg qd. Titrate: Max: 0.5mg bid. End-Stage Renal Disease: Max: 0.5mg qd. We recommend that the dose should be initiated at .125 mg to .25 mg qd and titrated up to .5 mg two times a day as tolerated. 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.

We used doses of ¹A to full dose depending on symptom relief and tolerability. Typically, the dose form for weight reduction or ADHD would be 1/16 to ¹A 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.

We propose a formulation at 1/8, ¹A and Vz of the current dosage. This will be appropriate for use in pediatric patients and in food as a health supplement.

All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.

It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and the scope of the appended claims. In addition, any elements or limitations of any invention or embodiment thereof disclosed herein can be combined with any and/or all other elements or limitations (individually or in any combination) or any other invention or embodiment thereof disclosed herein, and all such combinations are contemplated with the scope of the invention without limitation thereto.

REFERENCES

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Levin, ED, Rezvani, AH. (2002) "Nicotinic treatment for cognitive dysfunction." Curr Drug Targets CNS Neurol Disord. 1(4):423-31.

Maier, C, Schaller, G, Buranyi, B, et al. (2004) "The cholinergic system controls ghrelin release and ghrelin-induced growth hormone release in humans." J CHn Endocrinol Metab. 89(9):4729-33.

Mansvelder, HD, van Aerde, KI, Couey, JJ, et al. (2006) "Nicotinic modulation of neuronal networks: from receptors to cognition." Psychopharmacology (Berl) 184(3-4):292-305.

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Potter, AS, Newhouse, PA, Bucci, DJ. (2006) "Central nicotinic cholinergic systems: a role in the cognitive dysfunction in attention-deficit/hyperactivity disorder?" Behav Brain Res. 175(2):201-l 1. Rosecrans, JA, Krynock, GM, Newlon, PG, et al. (1978) "Central mechanisms of drugs as discriminative stimuli: Involvement of serotonin pathways." In: Colapaert FC, Rosecrans JA, eds. Stimulus properties: Ten years of progress. Amsterdam: Elsevier/North Holland Press, pp. 83-98.

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Nicotine Dependence. New York: Springer- Verlag., pp. 53-65. Ueno, K, Togashi, H, Matsumoto, M. (2002) "Alpha4beta2 nicotinic acetylcholine receptor activation ameliorates impairment of spontaneous alternation behavior in stroke-prone spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder." J Pharmacol Exp Ther. 302(l):95-100. West R, Ussher, M, Evans M, et al. (2006) "Assessing DSM-IV nicotine withdrawal symptoms: a comparison and evaluation of five different scales." Psychopharmacology (Berl) 184(3-4):619-27.

Wise, RA. (2006) "Role of brain dopamine in food reward and reinforcement." Philos Trans R Soc Lond B Biol Sci. 361(1471): 1149-58. Yamamoto, T. (2006) "Neural substrates for the processing of cognitive and affective aspects of taste in the brain." Arch Histol Cytol. 69(4):243-55.

Claims

CLAIMS We claim:

1. A method for modulating appetite and/or providing for weight reduction in a person or animal, said method comprising administering to the person or animal an effective amount of a compound of varenicline, or a composition comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof.

2. The method according to claim 1, wherein the person or animal is overweight.

3. The method according to claim 1, wherein the person or animal has been or is diagnosed as clinically obese.

4. The method according to claim 1, wherein the person is a non-smoker.

5. The method according to any preceding claim, wherein the person or animal is also treated with or is already being treated with other appetite suppression and/or weight reduction drugs.

6. The method according to claim 5, wherein said drug is orlistat, sibutramine, mazindol, xenical, rimonabant or diethylpropion, or an isomer or analog thereof.

7. The method according to claim 1, wherein said varenicline is administered orally to the person or animal.

8. The method according to claim 1, wherein said varenicline is provided in a chewing gum.

9. The method according to claim 1, wherein said method further comprises implementing a caloric reduction program, exercise, bariatric surgery, or any other therapy for suppressing appetite and/or reducing weight of the person or animal.

10. The method according to any preceding claim, wherein said method further comprises monitoring the weight of the person or animal over a period of time.

11. A method for treating a hyperactivity and/or an attention-deficit disorder in a person or animal, said method comprising administering to the person or animal an effective amount of a compound of varenicline, or a composition comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof.

12. The method according to claim 11, wherein said attention-deficit disorder is attention-deficit disorder (ADD) or attention-deficit hyperactivity disorder (ADHD).

13. The method according to claim 11, wherein the person or animal has been or is diagnosed as clinically hyperactive or as having an attention-deficit disorder.

14. The method according to claim 11 , wherein the person is a non-smoker.

15. The method according to any of claims 11 to 14, wherein the person or animal is also treated with or is already being treated with other drugs for a hyperactivity and/or an attention-deficit disorder.

16. The method according to claim 15, wherein said drug is is methylphenidate, atomoxetine, buproprion, an alpha-2 agonist (e.g. CLONIDINE), dexmethylphenidate, amphetamine, lisdexamfetamine, or dextroamphetamine, or an isomer or analog thereof.

17. The method according to claim 11, wherein said varenicline is administered orally to the person or animal.

18. The method according to claim 11, wherein said varenicline is provided in a chewing gum.

19. The method according to claim 11, wherein said method further comprises implementing other therapies for treating a hyperactivity and/or an attention-deficit disorder.

20. The method according to any of claims 11 to 19, wherein said method further comprises monitoring the person or animal for changes in a hyperactivity and/or an attention-deficit disorder over a period of time.

21. A composition comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof.

22. The composition according to claim 21, wherein said composition comprises: a) one or more appetite suppression and/or weight reduction drug; and/or b) one or more drugs used to treat hyperactivity and/or an attention-deficit disorder.

23. The composition according to claim 22, wherein said drug is orlistat, sibutramine, mazindol, xenical, rimonabant or diethylpropion, or an isomer or analog thereof.

24. The composition according to claim 22, wherein said drug is methylphenidate, atomoxetine, buproprion, an alpha-2 agonist (e.g. CLONIDINH), dexmethylphenidate, amphetamine, lisdexamfetamine, or dextroamphetamine, or an isomer or analog thereof.

25. A kit comprising in one or more containers varenicline or a composition comprising varenicline, or a pharmaceutically acceptable salt and/or analog thereof.

26. The kit according to claim 25, wherein said kit further comprises: a) one or more appetite suppression and/or weight reduction drug; and/or b) one or more drugs used to treat hyperactivity and/or an attention-deficit disorder.

27. The kit according to claim 26, wherein said drug is orlistat, sibutramine, mazindol, xenical, rimonabant or diethylpropion, or an isomer or analog thereof.

28. The kit according to claim 26, wherein said drug is methylphenidate, atomoxetine, buproprion, an alpha-2 agonist (e.g. CLONIDINE), dexmethylphenidate, amphetamine, lisdexamfetamine, or dextroamphetamine, or an isomer or analog thereof.

29. The kit according to any of claims 25 to 28, wherein said kit further comprises instructions or packaging material that describes 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.