MXPA99006785A

MXPA99006785A - Use of central cannabinoid receptor antagonists for regulating appetence

Info

Publication number: MXPA99006785A
Application number: MXPA/A/1999/006785A
Authority: MX
Inventors: Soubrie Philippe; Maruani Jeanne
Original assignee: Sanofiaventis
Priority date: 1997-01-28
Filing date: 1999-07-21
Publication date: 2000-07-01

Abstract

The invention concerns the use of a central cannabinoid receptor antagonist, on its own or combined with a compound for regulating metabolic disorders, in particular a&bgr;3-adrenergic receptor agonist, for preparing medicines useful for treating appetence disorders.

Description

Use of central cannabinoid receptor antagonists to regulate appetite.

DESCRIPTION OF THE INVENTION The present invention relates to the novel use of antagonists of central cannabinoid receptors or so-called CBi receptors. More particularly, the invention relates to the use of CBi receptor antagonists for the preparation of medicaments useful in the treatment of appetite disorders. The purpose of medicines useful in the treatment of appetite disorders are to regulate the desires of consumption, particularly desires to consume sugars, carbohydrates, alcohol or drugs and more generally to consume palatable ingredients. In the present description and in the claims, appetite disorders are understood as referring to: disorders associated with a substance and especially the abuse of a substance and / or dependence on a substance, - eating disorders, especially those that are responsible for causing Ref .: 30857 excessive weight, irrespective of its origin, for example: bulimia, appetite for sugars, diabetes not dependent on insulin. The substances are understood as referring to palatable ingredients such as sugars, carbohydrates, alcohols or medications. The present invention therefore further relates to the use of a CBi receptor antagonist for the preparation of medicaments useful in the treatment of bulimia and obesity, including obesity associated with type II diabetes. (non-insulin dependent diabetes), or more generally any disease resulting in the overweight patient, and in the treatment of drug abuse or drug dependence. Delta-9-tetrahydrocannabine, or? 9-THC, is the main active constituent extracted from Cannabis sativa (Tuner, 1985, in Marijuana, 8_4, Ed. Harvey, DY, IRL Press, Oxford). The effects of cannabinoids are due to an interaction with specific high affinity receptors coupled to G proteins. Two types of receptors are currently described: CBi receptors, which are predominantly present in the central nervous system (Devane et al., Molecular Fharmacology, 1988, 3_4_, 605-613), and CB2 receptors, which are present in the immune system (Nye et al / The Journal of Fharmacology and Experimental Therapeutics, 1985, 234, 784-791; Kaminski et al. , 1992, Molecular Fharmacology, 42, 736-742, Munro et al., Nature, 1993, 365, 61-65). The characterization of these receptors has been made possible by the development of synthetic ligands such as CP 55,940 (J. Pharmacol, Exp. Ther., 1988, 247, 1046-1051) and WIN 55212-2 (J. Pharmacol. Exp. Ther. ., 1993, 264, 1352-1363) and, more recently, by the discovery of the selective CB receptor antagonist SR 141716 A (M. Rinaldi-Car ona et al., FEBS Lett., 1994, 350, 240-244). . Families of compounds have an affinity for the cannabinoid receptor that have been described in various patents or patent applications, especially European patent application EP-576 357, which describes pyrazolo derivatives, and patent application WO 96 / 02248, which especially describe benzofuran derivatives. More particularly, N-piperidino-5- (4-chlorophenyl) -1- of 2,4-dichlorophenyl) -4-methylpyrazolo-3-carboxamide, also called SR 141716, of the formula its pharmaceutically acceptable salts and its solvates are described in European patent application EP-656 354 as CBi central receptor antagonists. SR 141716 A is the hydrochloride of SR 141716. It is known that delta-9-tetrahydrocannabine, whose name is Dronabinol which is not international property, is used in the treatment of anorexia, especially in patients suffering from AIDS (J. Pain Symptom Manage., 1995, 1_0 of 2), 89-97) or cancer (J. Palliat, Care, 1994, 10 of 1), 14-18). Additionally it is described that SR 141716 and its salts, which are antagonists of central cannabinoid receptors, that can be used in the treatment of appetite disorders, especially as anorexic agents, and in the treatment of disorders associated with the use of psychotropic substances .

Conventional anorectic agents cause a reduction in appetite which is generally independent of the foods to be consumed. Surprisingly, it has now been found that antagonists of CBi receptors have a specific property by interim selectivity on behavioral disorders of consumption that belong to appetite substances. Thus the administration of a CBi receptor antagonist m it possible to regulate the desire to consume non-essential food items such as excessive sugars, excess carbohydrates, alcohol or drugs. In fact, after conducting tests on animals, a novel behavior of the animal has been noted: the animal tests have revealed a novel behavior: the animal does not show greater spontaneous appetite for the ingredient, for example sugar or alcohol, which commonly brings pleasure to this. This lack of appetite also manifests when the animal has been pretreated with a known neuropeptide to increase appetite, for example neuropeptide Y (NPY).

According to one of its aspects, the present invention relates to the use of a CBi receptor antagonist for the preparation of medicaments useful in the treatment of appetite disorders. The CBi receptor antagonists suitable for the purposes of the invention are particularly the compounds of the formula wherein - Ri, is hydrogen, a fluorine, a hydroxyl, an alkoxy of 1 to 5 carbon atoms, an alkylthio of 1 to 5 carbon atoms, a hydroxyalkoxy of 1 to 5 carbon atoms, , a group -NR10R11, a cyano, an alkylsulfonyl of 1 to 5 carbon atoms or an alkylsulfinyl of 1 to 5 carbon atoms; - R2 and Rj are an alkyl of 1 to 4 carbon atoms or, together with the nitrogen atom to which they are attached, forming a heterocyclic radical of 5 to 10 members saturated or unsaturated which is unsubstituted or monosubstituted or polysubstituted by an alkyl of 1 to 3 carbon atoms or by an alkoxy of 1 to 3 carbon atoms; - R4, R5, R6, R, Re and R9 are each independently hydrogen, a halogen or a trifluoromethyl, and if Rj is a fluorine, R4 / R5, R6, R7, Rs and / or Rg can also be a fluoromethyl, with the provision that at least one of the substituents R4 or R7 is other than hydrogen; and - Rio and Rn are each independently hydrogen or an alkyl of 1 to 5 carbon atoms or Rio and Rn, together with the nitrogen atom to which they are attached, form a heterocyclic radical selected from pyrrolidin-1-yl, piperidin -1-yl, orpholin-4-yl and piperazin-1-yl, which are unsubstituted or substituted by an alkyl of 1 to 4 carbon atoms, and their salts and their solvates. More particularly, the present invention relates to the use of N-piperidino-5- (4-chlorophenyl) -1- of 2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide, its pharmaceutically acceptable salts and its solvates for preparation of medicines useful in the treatment of appetite disorders. According to the present invention, the antagonists of the CBi receptors can also be used in association with another active ingredient for the preparation of medicaments useful in the treatment of appetite disorders, especially in the treatment of disorders of eating behaviors, it is possible to use a pharmaceutical composition comprising a CBi receptor antagonist in association with a compound for the regularization of metabolic disorders, especially an ß3 adrenergic receptor agonist, hereinafter called a ß3 agonist. Thus the present invention additionally relates to pharmaceutical compositions which contain a CBi receptor antagonist and a regulator of metabolic disorders, for example a hypolipidemic, hipollemic or lipolytic. More particularly, the present invention relates to pharmaceutical compositions containing a CBi receptor antagonist and a β3 agonist. The p3 agonists which can be used according to the present invention are the compounds of the formula (III) wherein X is hydrogen, a halogen a trifluoromethyl or an alkyl of 1 to 4 carbon atoms; R is a hydrogen or a methyl which is unsubstituted or substituted by a carboxyl or an alkoxycarboxyl in which the alkoxy is from 1 to 6 carbon atoms, and its pharmaceutically acceptable salts, indicated in EP 0 211 721 and EP 0 303 546 as intestinal spasmolytics. Among the compounds of the formula (III), the following compounds: * 2- [(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * 2- [(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) amino] -1- (3-chlorophenyl) -ethanol; * 2- [(7-ethoxycarbonylmethoxy-1,2,4,4-tetrahydronaphth-2-yl) amino] -1- (3-chlorophenyl) ethanol; * 2- [(7-ethoxycarbonylmethoxy-1,3,4,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * (1R, 2RS) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * 1S, 2'RS) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * (+) - (IR) -2- [(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * (+) - (lS) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * (-) - (IR) -2- [(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * (-) - (lS) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; * N- [(2S) -7-ethoxycarbonylmethoxy-1, 2,3,4-tetrahydronaphth-2-yl] - (2R) -2- (3-chlorophenyl) -2-hydroxyethanamine; and * N- [(2R) -7-methoxycarbonylmethoxy-1, 2,3,4-tetrahydronaphth-2-yl] - (2R) -2- (3-chlorophenyl) -2-hydroxyethanamine, and their pharmaceutically acceptable salts are particularly advantageous. N- [(2S) -7-Ethoxycarbonylmethoxy-1, 2,3,4-tetrahydronaphth-2-yl] - (2R) -2- of 3-chlorophenyl) -2-hydroxyethane ina (SR 58611) and its salts pharmaceutically acceptable are particularly very advantageous, especially its salt with hydrochloric acid, SR 58611 A.

Other ß3 antagonists which can be used according to the present invention are the compounds of the formula A (IV) where - n is l, 2 or 3; - A is a benzofuran-2-yl or phenyl which is unsubstituted or substituted, by one or two carbon atoms. halogen or an alkyl of 1 to 4 carbon atoms or a trifluoromethyl; - R 'is: - hydrogen; - an alkyl of 1 to 6 carbon atoms; - a functional group selected from the following groups: hydroxyl; alkoxy of 1 to 6 carbon atoms; alkenyloxy having 2 to 6 carbon atoms; alkynyloxy having 2 to 6 carbon atoms; cycloalkoxy of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkoxy of 1 to 6 carbon atoms; benzyloxy; phenoxy; mercapto; alkylthio of 1 to 6 carbon atoms; alkenylthio of 2 to 6 carbon atoms; alkenylthio of 2 to 6 carbon atoms; cycloalkylthio of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylthio of 1 to 6 carbon atoms; benzylthio; phenylthio; alkylsulfinyl of 1 to 6 carbon atoms; alkenylsulfinyl having 2 to 6 carbon atoms; alkynylsulfinyl having 2 to 6 carbon atoms; cycloalkylsulfinyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylsulfinyl of 1 to 6 carbon atoms; benzylsulfinyl; phenylsulfinyl; alkylsulfinyl of 1 to 6 carbon atoms; alkenylsulfonyl of 2 to 6 carbon atoms; alkynylsulfonyl of 2 to 6 carbon atoms; cycloalkylsulfonyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylsulfonyl of 1 to 6 carbon atoms; benzylsulfonyl; phenylsulfonyl; cyano; nitro; Not me; which are unsubstituted or substituted by one or two identical or different radicals selected from the alkyl groups of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms; alkyl of 1 to 6 atoms carbon, benzyl and phenyl; alkoxycarbonyl in which the alkoxy is from 1 to 6 carbon atoms; alkenyloxycarbonyl of 2 to 6 carbon atoms; alkynyloxycarbonyl of 2 to 6 carbon atoms; cycloalkoxycarbonyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkoxycarbonyl of 1 to 6 carbon atoms; benzyloxycarbonyl; phenoxycarbonyl; or carbamoyl which are unsubstituted or substituted in the amino group by one or two identical or different radicals selected from the alkyl groups of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms , cycloalkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms; alkyl of 1 to 6 carbon atoms, benzyl and phenyl; a group R '' 'selected from the following groups: alkyl of 1 to 6 carbon atoms substituted by a functional group; alkenyl of 2 to 6 carbon atoms substituted by a functional group; alkynyl of 2 to 6 carbon atoms substituted by a functional group; alkylphenyl of 1 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; alkenylphenyl of 2 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; alkynylphenyl of 2 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; benzyl substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; and phenyl which is unsubstituted or substituted by an alkyl of 1 to 6 carbon atoms or by a functional group, the functional group is as defined above; a group O-R '' ', S-R' '', SO-R '' 'or S02-R' '', in which R '"is as defined above; a group NR '"R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or PT' 'and R °, together with the nitrogen to which they join, forming a group selected from the pyrrolidino, piperidino and morpholino groups, a group COOR '' 'or a group CO-SR' '', in which R '' 'is as defined above; CONR '' R °, in which R '' 'is as defined above and R ° is hydrogen or is as defined above for R' '', or R '' 'and R °, together with the nitrogen to which they come together, forming a selected group of the pyrrolidino, piperidino and morpholino groups; a group SO2NR '"R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or R' '' and R °, together with nitrogen at which they join, forming a selected group of the pyrrolidino, piperidino and morpholino groups, t R "is hydrogen; a halogen; an alkyl of 1 to 6 carbon atoms; a functional group as defined above; a group OR '' ', R' '' being as defined above; a group COOR '' ', R '' 'being as defined above; or a group C0NR '' 'R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or R' '' and R °, together with the nitrogen to which they are bound, forming a group selected from the pyrrolidino, piperidino and morpholino groups, W is a direct bond or an oxygen atom; X 'is hydrogen / an alkyl of 1 to 6 carbon atoms or an alkylcarbonyl of 1 to 6 carbon atoms; Y is hydrogen or a group A '-CH (OH) -CH2-, A' is identical to A but other than benzofuran-2-yl; or - X 'and Y, taken together, form a methylene group optionally substituted by a carbonyl alkoxy in which the alkoxy is from 1 to 6 carbon atoms; an ethylene group optionally substituted by an oxo group; or a 1,3-propylene group; Z is hydrogen or an alkyl of 1 to 6 carbon atoms, and their pharmaceutically acceptable salts, indicated in EP 0 255 415 as intestinal spasmolytics. Other ß3 agonists which may also be used according to the present invention are the compounds of the formula wherein - E is hydrogen, an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a phenyl, a nitro, a halogen atom or a trifluoromethyl; - L is hydrogen, an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a phenyl, nitro or a halogen atom; or E and L together are a group -CH = CH-CH = CH- or -CH2-CH2-CH2-CH2-; and - G is hydrogen, a chlorine atom, a hydroxyl or an OG 'group, in which G' is an alkyl of 1 to 4 carbon atoms which is unsubstituted or substituted by a hydroxy, alkoxy of 1 to 4 atoms carbon, alkoxycarbonyl of 1 to 4 carbon atoms, carboxyl or cycloalkyl of 3 to 7 carbon atoms; a cycloalkyl of 3 to 7 carbon atoms; or an alkanoyl of 2 to 4 carbon atoms, and their pharmaceutically acceptable salts, indicated in EP 0 436 435 as intestinal spasmolytics. Among the compounds of formula (V), N - [(2R) - (6-hydroxy-1, 2,3,4-tetrahydronaphth-2-yl) methyl] - (2R) -2-hydroxy-2- (3 chlorophenyl) ethanamine (SR 59104), N - [(2R) - (7-methoxy-l, 2,3,4-tetrahydronaphth-2-yl) methyl] - (2R) -2-hydroxy-2- (3 chlorophenyl) ethanamine (SR 59119) and its pharmaceutically acceptable salts are the particularly advantageous compounds. Other advantages of β3 agonists according to the present invention are compound BRL 35135 described in EP 23385; the compound CL 316243 described in US 5 061 727; the compound AZ 002 described in EP 218440; the BMS compound 187257 described in US 5 321 036; the compound ZD 7114 described in EP 473 285; the compound RO 40-2148 described in Am. J. Clin. Nutr., 1992, 5_5 (1, Suppl.), 249S-251S; and the products described in the following patents / patent applications: WO 96/35671, WO '96/35670, WO 96/16038, WO 96/04233, WO 95/33724, WO 95/29159, EP 659737, WO 95 / 04047, EP 516349, EP 473285, EP 23385, EP 21636, EP 7205, JP 08198866, JP 08165276, JP 08157470, WO 96/16938, EP 714883, WO 96/04234, US 5 488 064, US 5 482 971, US 5 491 134, WO 95/29159, WO 95/33724, ZA 9409874, WO 95/29903, US 5 461 163, WO 95/25104, EP 659737, JP 07112958, WO 95/8527, WO 95/07284, JP 07025756 , WO 95/03289, WO 95/04047, WO 95/01170, WO 94/29290, US 5 373 020, JP 06293664, WO 94/12166 and US 5 451 677. For use as a medicament, an antagonist compound of the CBi receptor, by itself or in association with a β3 agonist, must be formulated as a pharmaceutical composition. In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, local or rectal administration, the active ingredient, by itself or in association with another active ingredient, can be administered to animals and humans in unitized forms of administration mixed with pharmaceutically conventional carriers. The unit forms Suitable administration forms include oral forms such as tablets, gelatin capsules, powders, granules and solutions or suspensions to be taken orally, sublingual and buccal administration forms, aerosol, implants, subcutaneous, intramuscular, intravenous, intranasal or intraocular administration forms and rectal administration forms. In the pharmaceutical compositions of the present invention, the active principle or the active ingredients are generally formulated in unit doses. The unit dose contains from 0.5 to 1000 mg, advantageously from 1 to 500 mg and preferably from 2 to 200 mg of CBi receptor antagonist per unit dose per daily administration. . In cases where 2 active ingredients are associated, the unit dose contains from 0.5 to 600 mg, advantageously from 1 to 400 mg and preferably from 2 to 200 mg of the CBi receptor antagonist compound and from 0.5 to 600 mg, advantageously from 2 to 400 mg and preferably from 10 to 250 mg of the other active ingredient, especially a β3 agonist - When a solid composition is prepared in the form of tablets, a wetting agent such as sodium lauryl sulfate which can be added to the micronized active ingredient (s) or not micronized and the whole is mixed with a pharmaceutical carrier such as silica, starch, lactose, magnesium esrearate, talc or the like. The tablets may be coated with sucrose, a variety of polymers or other appropriate substances, or other of them may be treated to have a sustained or delayed activity and to release a predetermined amount of active ingredient continuously. A preparation in the form of gelatin capsules is obtained by mixing the active principle or active ingredients with a diluent, such as a glycol or a glycerol ester, and incorporating the resulting mixture into hard or soft gelatin capsules. A preparation in the form of a syrup or an elixir may contain the active ingredient or the active ingredients together with a sweetener, which is preferably free of calories, methylparaben and propylparaben as the antiseptics, a flavoring and an appropriate color. Dispersible powders in water or granules may contain the active principle or the active ingredients mixed with dispersants or wetting agents or with suspending agents such as polyvinylpyrrolidone or polyvidone, as well as with sweeteners or taste correctors.

The rectal administration is carried out using suppositories, which are prepared with binders that melt at rectal temperature, for example cocoa butter or polyethylene glycols. Parenteral administration is carried out using aqueous suspensions, isotonic saline solutions or sterile injectable solutions containing pharmacologically compatible dispersing agents and / or solubilizers, for example propylene glycol or butylene glycol. Thus, to prepare an aqueous solution for intravenous injection, it is possible to use a cosolvent, for example an alcohol such as ethanol or a glycol such as polyethylene glycol or propylene glycol, and a hydrophilic surfactant such as T eens 80. To prepare an oil solution for Intramuscular injection, the active ingredient can be solubilized with a triglyceride or a glycerol ester. A transdermal administration can be carried out using the patches in a multilamellar form or with a reservoir in which the active principle is in the alcoholic solution. The active principle or the active ingredients can also be formulated as microcapsules or microspheres, optionally with one or more conveyors or additives. The active principle or the active ingredients can also be present in the form of complexes with a cyclodextrin, for example a-, β- or β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin or methyl-β-cyclodextrin. Among the sustained release forms useful in the case of chronic treatments, it is possible to use implants. These may be prepared in the form of an oily suspension or in the form of a suspension of εphere in an isotonic medium. According to another aspect of the invention, the CBi receptor antagonist and the regulator of metabolic disorders, especially the β-agonist, can be administered simultaneously, sequentially or over a period of time in the treatment of appetite disorders, especially in the treatment of disorders of eating behaviors. The invention is therefore additionally related to a kit or kit for the treatment of appetite disorders by administration, simultaneously, sequentially or over a period of time, of a CBi receptor antagonist and a regulator of metabolic disorders, especially a β-agonist, in which the equipment of said CBi receptor antagonist and said regulator of metabolic disorders, especially said β3 agonist, are in separate compartments and optionally in different packages. More particularly, said equipment contains N-piperidino-5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methylpyrosso-3-carboxamide, one of its pharmaceutically acceptable salts or one of its solvates, and N- (2S) -7-ethoxycarbonylmethoxy-1, 2,3, -tetrahydronaphth-2-yl] - (2R) -2- (3-chlorophenyl) -2-hydroxyethanamine or one of its pharmaceutically acceptable salts. According to another of its aspects, the invention additionally relates to a method of treating appetite disorders, especially a method of treating disorders of eating behaviors, which consists of administering, to a subject in need thereof, a effective amount of a CBi receptor antagonist (therapeutically) as defined above. Said CBi receptor antagonist can advantageously be used in association with a regulator of metabolic disorders, especially a β3 agonist, as defined above. In particular, the CBi receptor antagonist and the metabolic disorder regulator they can be administered simultaneously, sequentially or over a period of time.

TEST No. 1: Effect of SR 141716 A on the intake of a sucrose solution in rats The experimentation is carried out according to W.C. Lynch et al., Physioi. Behav., 1993, 54, 877-880. Male Sprague-Da ley rats weighing 190 to 210 g are under a normal light cycle (from 7 am to 7 pm) and receive water and feed by adding libitum. For 6 days, between 11 am and 3 p, the food and water bottles are removed and the rare ones are given a 5% sucrose solution to drink. Rats that drank less than 3 g of sucrose solution are eliminated. On the seventh day the test is carried out according to the following procedure: 9 a: the food is removed, 10 am: oral administration of SR 141716 A, 11 am = A: the introduction of bottles containing a heavy sucrose solution, A + 1 hour, A + 2 hours, A + 3 hours, A + 4 hours: The consumption of sucrose is measured by the weight of the bottles.

TABLE 1 * < 0.05; ** p < 0.01, Dunnett's test It is observed from the results reported in TABLE 1 that the administration of SR 141716 A greatly reduces the consumption of the aqueous solution of sugar at or above a dose of 0.3 mg / kg.

TEST No. 2: Effect of SR 141716 A on the consumption of an alcohol solution in mice The male mice of C 57 BL 6 (Iffa-Credo) are isolated on the day of their arrival in an animal housing under an opposite cycle (at night from 10 am to 10 pm) with 2 bottles filled with water. After 1 week, one of the water bottles is replaced with a bottle filled with 10% alcohol solution for 6 hours of the test. Every day, 30 minutes before the alcohol bottle is introduced, the mice are treated subcutaneously with SR 141716 A. The consumed amounts of alcohol and water are measured after 6 hours. The test is repeated for 4 days.

TABLE 2 p < 0.01, Dunnett's test The results show that the consumption of alcohol decreases very considerably for treated animals: from 1.9 ± 0.1 g for an untreated animal to 1.0 ± 0.2 g for an animal receiving 3 mg / kg of SR 141716 A; water consumption increased in parallel: from 1.1 ± 0.1 to 1.6 ± 0.3 g.

EXAMPLE 1 The gelatin capsule containing a dose of 1 mg of CBi receptor antagonist Micronized SR 141716 1.00 mg Corn starch 51.00 mg Lactose monohydrate 103.33 mg Polividone 4.30 mg Sodium lauryl sulfate 0.17 mg Sodium carboxymethylcellulose reticulates to 8.50 mg purified water: QS to moisturize the granulation of magnesium stearate 1.70 mg For the no. 3 the opaque white gelatin capsule was filled to 170 mg EXAMPLE 2 The gelatin capsule containing a dose of 10 mg CBi receptor antagonist Micronized SR 141716 10.00 mg Corn Starch 51.00 mg Lactose monohydrate 94.33 mg Polividone 4.30 mg Sodium lauryl sulfate 0.17 mg Sodium carboxymethylcellulose crosslinked 8.50 mg purified water: QS to moisturize the granulation of magnesium stearate 1.70 mg For the no. 3 the opaque white gelatin capsule was filled to 170 mg EXAMPLE 3 The gelatin capsule containing a dose of 30 mg CBi receptor antagonist Micronized SR 141716 30.00 mg Corn starch 51.00 mg Lactose monohydrate 74.33 mg Polividone 4.30 mg Sodium lauryl sulfate 0.17 mg Sodium carboxymethylcellulose crosslinked 8.50 mg Purified water: QS to wet the granulation of magnesium stearate 1.70 mg For the no »3 the opaque white gelatin capsule was filled to 170 g 32 6. The use according to claim 5, characterized by the preparation of medicaments useful in the treatment of obesity with non-insulin-dependent diabetes. 7. The use according to claim 1, characterized by the preparation of drugs useful in the treatment of any disease resulting in the overweight patient. 8. The use according to claim 1, characterized by the preparation of medicaments useful in the treatment of bulimia. 9. The use according to claim 1, characterized by the preparation of medicaments useful in the treatment of drug abuse or drug dependence.

. The use according to claims 1 to 9, characterized in that the CBi receptor antagonist is a compound of the formula 33 wherein Ri is hydrogen, a fluorine, a hydroxyl, an alkoxy of 1 to 5 carbon atoms, an alkylthio of 1 to 5 carbon atoms, a hydroxyalkoxy of 1 to 5 carbon atoms, a group -NR10Rn, a cyano, an alkylsulfonyl of 1 to 5 carbon atoms or an alkylsulfinyl of 1 to 5 carbon atoms; - R2 and R3 are an alkyl of 1 to 4 carbon atoms or, together with the nitrogen atom to which they are attached, forming a saturated or unsaturated 5- to 10-membered heterocyclic radical which is unsubstituted or monosubstituted or polysubstituted by a alkyl of 1 to 3 carbon atoms or an alkoxy of 1 to 3 carbon atoms; - R 4, R 5 R b R 7, R s and R 9 are each independently hydrogen, a halogen or a trifluoromethyl, and if Ri is a fluorine, R 4, R 5, Rs, R 7, R 8 and / or R g can also be a fluoromethyl, with the provision that at least one of the substituents R4 or R7 is other than hydrogen; Y 3. 4 - Rio and Rn are each independently hydrogen or an alkyl of 1 to 5 carbon atoms or Rio and Rn, together with the nitrogen atom to which they are attached, form a heterocyclic radical selected from pyrrolidin-1-yl, piperidin- 1-yl, morpholin-4-yl and piperazin-1-yl, which are unsubstituted or substituted by an alkyl of 1 to 4 carbon atoms, one of its salts and one of its solvates. 11. The use according to claim 10, characterized in that the CBi receptor antagonist N-piperidino-5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methylpyrazolo-3-carboxamide, one of its salts pharmaceutically acceptable or one of its solvates. 12. The use according to any of claims 1 to 8, 10 or 11, characterized in that the CBi receptor antagonist is associated with a regulator of metabolic disorders. 13. The use according to claim 12, characterized in that said regulator of the metabolic disorders is a β3 antagonist. 14. The use according to claim 13, characterized in that said β5 agonist in a compound of the formula wherein - X is hydrogen, a halogen a trifluoromethyl or an alkyl of 1 to 4 carbon atoms; - R is hydrogen or a methyl which is unsubstituted or substituted by a carboxyl or an alkoxycarboxyl in which the alkoxy is from 1 to 6 carbon atoms or one of its pharmaceutically acceptable salts, . The use according to claim 14, characterized in that said β3 agonist is N- [(2S) -7-ethoxycarbonylmethoxy-1,2,3,4-tetrahydronaphth-2-yl] - (2R) -2- (3- chlorophenyl) -2-hydroxyethamine or one of its pharmacologically acceptable salts. 16. The use according to claim 13, characterized in that said β3 agonist is a compound of the formula 36 TO wherein n is l, 2 or 3; - A is a benzofuran-2-yl or phenyl which is unsubstituted or substituted by one or two halogen atoms or by an alkyl of 1 to 4 carbon atoms or a trifluoromethyl; - R 'is :. - hydrogen; - an alkyl of 1 to 6 carbon atoms; - a functional group selected from the following groups: hydroxyl; alkoxy of 1 to 6 carbon atoms; alkenyloxy having 2 to 6 carbon atoms; alkynyloxy having 2 to 6 carbon atoms; cycloalkoxy of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkoxy of 1 to 6 carbon atoms; benzyloxy; phenoxy; mercapto; alkylthio of 1 to 6 carbon atoms; alkenylthio of 2 to 6 carbon atoms; alkenylthio of 2 to 6 carbon atoms; cycloalkylthio of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylthio of 1 to 6 carbon atoms; benzylthio; phenylthio; 37 alkylsulfinyl of 1 to 6 carbon atoms; alkenylsulfinyl having 2 to 6 carbon atoms; alkynylsulfinyl having 2 to 6 carbon atoms; cycloalkylsulfinyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylsulfinyl of 1 to 6 carbon atoms; benzylsulfinyl; phenylsulfinyl; alkylsulfinyl of 1 to 6 carbon atoms; alkenylsulfonyl of 2 to 6 carbon atoms; alkynylsulfonyl of 2 to 6 carbon atoms; cycloalkylsulfonyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylsulfonyl of 1 to 6 carbon atoms; benzylsulfonyl; phenylsulfonyl; cyano; nitro; Not me; which are unsubstituted or substituted by one or two identical or different radicals selected from the alkyl groups of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms; alkyl of 1 to 6 carbon atoms, benzyl and phenyl; alkoxycarbonyl in which the alkoxy is from 1 to 6 carbon atoms; alkenyloxycarbonyl of 2 to 6 carbon atoms; alkynyloxycarbonyl of 2 to 6 carbon atoms; cycloalkoxycarbonyl of 3 to 8 carbon atoms; 38 cycloalkyl of 3 to 8 carbon atoms; alkoxycarbonyl of 1 to 6 carbon atoms; benzyloxycarbonyl; phenoxycarbonyl; or carba oyl which are unsubstituted or substituted in the amino group by one or two identical or different radicals selected from the alkyl groups of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms carbon, cycloalkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms alkyl of 1 to 6 carbon atoms, benzyl and phenyl; a group R '' 'selected from the following groups: alkyl of 1 to 6 carbon atoms substituted by a functional group; alkenyl of 2 to 6 carbon atoms substituted by a functional group; alkynyl of 2 to 6 carbon atoms substituted by a functional group; alkylphenyl of 1 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; alkenylphenyl of 2 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; alkynylphenyl of 2 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; benzyl substituted on phenyl 39 by an alkyl of 1 to 6 carbon atoms or by a functional group; and phenyl which is unsubstituted or substituted by an alkyl of 1 to 6 carbon atoms or by a functional group, the functional group is as defined above; a group O-R '' ', S-R "', S02-R" 'or S0-R' '', in which R '' 'are as defined above; a group NR '"R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '", or R' '' and R °, together with nitrogen at that they bind, forming a selected group of the pyrrolidino, piperidino and morpholino groups; a COOR group '' 'or a group CO-SR' '', in which R '' 'is as defined above; a group C0NR '' 'R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or R' '' and R °, together with the nitrogen to which they are bound, forming a group selected from the pyrrolidino, piperidino and morpholino groups; a group S02NR '' 'R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or R' '' and R °, together with nitrogen which they join, forming a 40 selected group of the pyrrolidino, piperidino and morpholino groups, R "is hydrogen, a halogen, an alkyl of 1 to 6 carbon atoms, a functional group as defined above, a group OR '' ', R' '' being as previously defined, a group COOR '' ', R' '' being as defined above, or a group CONR '' 'R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or R' '' and R °, together with the nitrogen to which they are bound, forming a group selected from the pyrrolidino, piperidino and morpholino groups, W is a direct bond or an atom oxygen, X 'is hydrogen, an alkyl of 1 to 6 carbon atoms or an alkylcarbonyl of 1 to 6 carbon atoms, Y is hydrogen or a group A' -CH (OH) -CH2-, A 'is identical to A but another that benzofuran-2-yl, or X 'and Y, taken together, form a methylene group optionally substituted by an alkoxycarbonyl in which the alkoxy is 1 to 6 carbon atoms; an ethylene group optionally substituted by an oxo group; or a 1,3-propylene group; 41 - Z is a hydrogen or an alkyl of 1 to 6 carbon atoms, or a pharmaceutically acceptable salt thereof, 17. The use according to claim 13, characterized in that said β3 agonist is a compound of the formula wherein - E is hydrogen, an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a phenyl, a nitro, a halogen atom or a trifluoromethyl; - L is hydrogen, an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a phenyl, a nitro or a halogen atom; or E and L together are a group -CH = CH-CH = CH- or -CH2-CH2-CH2-CH2-; and - G is hydrogen, a chlorine atom, a hydroxyl or an OG 'group, in which G' is an alkyl of 1 to 4 carbon atoms which is unsubstituted or substituted by a hydroxyl, alkoxy of 1 to 4 atoms of carbon, alkoxycarbonyl of 1 to 4 carbon atoms, 42 cycloalkylcarboxyl of 3 to 7 carbon atoms; a cycloalkyl of 3 to 7 carbon atoms; or an alkanoyl of 2 to 4 carbon atoms, or a pharmaceutically acceptable salt thereof, 18. The use according to claim 13, characterized in that the CBi receptor antagonist is N-piperidino-5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methylpyrazolo-3-carboxamide, one of its pharmacologically acceptable salts or one of its solvates and the β3 agonist is N - [(2S) -7-ethoxycarbonylmethoxy-1,2,3,4-tetrahydronaphth-2-yl] - (2R) -2- (3-chlorophenyl) -2-hydroxyethamine or one of pharmaceutically acceptable salts thereof. 19. A pharmaceutical composition characterized in that it contains a CBi receptor antagonist and a regulator of metabolic functions with a pharmaceutical excipient.

. A pharmaceutical composition according to claim 19, characterized in that said regulator of metabolic functions is a β3 agonist. 29 EXAMPLE 4 A tablet containing a dose of 30 mg of CBi receptor antagonist Micronized SR 141716 30.00 mg lactose monohydrate QS Corn starch 40.00 mg Hydroxypropylmethylcellulose 6 cP 5.00 mg Purified water: QS for moisturizing the granulation of cross-linked sodium carboxymethylcellulose 10.00 mg Magnesium stearate 2.00 mg For a finished tablet of 200 mg EXAMPLE 5 One tablet containing 30 mg of CBi receptor antagonist and 200 mg of the β3-agonist Micronized SR 141716 30.00 mg SR 58611 A expressed as the base 200.00 mg Lactose monohydrate QS Polividone 15.00 mg Purified water: QS to moisturize the granulation of the cross-linked sodium carboxymethylcellulose 10.00 mg Magnesium stearate 5.00 mg For a finished tablet of 500 mg EXAMPLE 6 A tablet containing 10 mg of CBi receptor antagonist and 100 mg of β3 agonist Micronized SR 141716 10.00 mg SR 58611 A expressed as the base 100.00 mg Corn starch 30 mg Lactose monohydrate QS Hydroxypropylmethylcellulose 6 cP 5.00 mg Purified water: QS for moisturizing the starch granulation of sodium carboxymethylcellulose 6.00 mg Magnesium stearate 3.00 mg For a finished tablet of 300 mg It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers. Having described the invention as above, property is claimed as contained in the following:

Claims

31 CLAIMS 1. The use of a CBi receptor antagonist characterized for the preparation of medicaments useful in the treatment of appetite disorders.
2. The use according to claim 1, characterized by the preparation of drugs intended to regulate the desired consumption.
3. The use according to claim 1, characterized by the preparation of medicaments useful in the treatment of disorders associated with a substance.
4. The use according to claim 1, characterized by the preparation of medicaments useful in the treatment of disorders of eating behaviors.
5. The use according to claim 1, characterized by the preparation of medicaments useful in the treatment of obesity. 21. A pharmaceutical composition according to claim 19 or 20, characterized in that CBi receptor antagonist is a compound of the formula wherein - Ri, is hydrogen, a fluorine, a hydroxyl, an alkoxy of 1 to 5 carbon atoms, an alkylthio of 1 to 5 carbon atoms, a hydroxyalkoxy of 1 to 5 carbon atoms, a group -NRioRn , a cyano, an alkylsulfonyl of 1 to 5 carbon atoms or an alkylsulfinyl of 1 to 5 carbon atoms; - R2 and R3 are an alkyl of 1 to 4 carbon atoms or, together with the nitrogen atom to which they are attached, forming a saturated or unsaturated 5- to 10-membered heterocyclic radical which is unsubstituted or monosubstituted or polysubstituted by a alkyl from 1 to 3 carbon atoms or by an alkoxy of 1 to 3 carbon atoms; - R4, Rs, Rß / R7, R? and g are each independently hydrogen, a halogen or a trifluoromethyl, and if Ri is a fluorine, R4, R5, R6, R7, Re and / or Rg can also be a fluoromethyl, with the proviso that at least one of the substituents R4 or R7 is other than hydrogen; Y - Rio and Rn are each independently hydrogen or an alkyl of 1 to 5 carbon atoms or Rio and Rn, together with the nitrogen atom to which they are attached, form a heterocyclic radical selected from pyrrolidin-1-yl, piperidin- 1-yl, morpholin-4-yl and piperazin-1-yl, which are unsubstituted or substituted by an alkyl of 1 to 4 carbon atoms, one of its salts and one of its solvates. 22. A pharmaceutical composition according to claim 21, characterized in that the CBi receptor antagonist is N-piperidino-5- (4-chlorophenyl) -1- (2,4-dicyclophenyl) -4-methylpyrazolo-3-carboxamide, one of its pharmaceutically acceptable salts or one of its solvates. 23. A pharmaceutical composition according to any of claims 20 to 22, characterized in that the β3 agonist is a compound of the formula wherein - X is hydrogen, a halogen, a trifluoromethyl or an alkyl of 1 to 4 carbon atoms; R is hydrogen or a methyl which are unsubstituted or substituted by a carboxyl or an alkoxycarbonyl in which the alkoxy is from 1 to 6 carbon atoms, or a pharmaceutically acceptable salt thereof. 24. A pharmaceutical composition according to any of claims 20 to 22, characterized in that the β3 agonist is a compound of the formula wherein n is l, 2 or 3; A is a benzofuran-2-yl or phenyl which is unsubstituted or substituted by one or two halogen atoms or by an alkyl of 1 to 4 carbon atoms or a trifluoromethyl; - R 'is: - hydrogen; - an alkyl of 1 to 6 carbon atoms; - a functional group selected from the following groups: hydroxyl; alkoxy of 1 to 6 carbon atoms; alkenyloxy having 2 to 6 carbon atoms; alkynyloxy having 2 to 6 carbon atoms; cycloalkoxy of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms of 1 to 6 carbon atoms; benzyloxy; phenoxy; mercapto; alkylthio of 1 to 6 carbon atoms; alkenylthio of 2 to 6 carbon atoms; alkenylthio of 2 to 6 carbon atoms; cycloalkylthio of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylthio of 1 to 6 carbon atoms; benzylthio; phenylthio; alkylsulfinyl of 1 to 6 carbon atoms; alkenylsulfinyl having 2 to 6 carbon atoms; alkynylsulfinyl having 2 to 6 carbon atoms; cycloalkylsulfinyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylsulfinyl of 1 to 6 carbon atoms; benzylsulfinyl; phenylsulfinyl; alkylsulfinyl of 1 to 6 carbon atoms; alkenylsulfonyl of 2 to 6 carbon atoms; alkynylsulfonyl of 2 to 6 carbon atoms; cycloalkylsulfonyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkylsulfonyl of 1 to 6 carbon atoms; benzylsulfonyl; phenylsulfonyl; cyano; nitro; Not me; which are unsubstituted or 'replaced by one or. two identical or different radicals selected from the alkyl groups of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms alkyl of 1 to 6 carbon atoms, benzyl and phenyl; alkoxycarbonyl in which the alkoxy is from 1 to 6 carbon atoms; alkenyloxycarbonyl of 2 to 6 carbon atoms; alkynyloxycarbonyl of 2 to 6 carbon atoms; cycloalkoxycarbonyl of 3 to 8 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkoxycarbonyl of 1 to 6 carbon atoms; benzyloxycarbonyl; phenoxycarbonyl; or carbamoyl which are unsubstituted or substituted in the amino group by one or two identical or different radicals selected from the alkyl groups of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms alkyl of 1 to 6 carbon atoms, benzyl and phenyl; a group R '' 'selected from the following groups: alkyl of 1 to 6 carbon atoms substituted by a functional group; alkenyl of 2 to 6 carbon atoms substituted by a functional group; alkynyl of 2 to 6 carbon atoms substituted by a functional group; alkylphenyl of 1 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; alkenylphenyl of 2 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; alkynylphenyl of 2 to 6 carbon atoms substituted on the phenyl by an alkyl of 1 to 6 carbon atoms or by a functional group; benzyl substituted on the phenyl by an alkyl of 1 to 6 carbon atoms, or by a functional group; and phenyl which is unsubstituted or substituted by an alkyl of 1 to 6 carbon atoms or by a functional group, the functional group is as defined above; a group O-R '' ', S-R' '', S02-R '' 'or S02-R' '', in which R '' 'are as defined above; a group NR '"R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or R' '' and R °, together with the nitrogen to which they are bound, formed a selected group of the pyrrolidino, piperidino and morpholino groups, a group COOR '' 'or a group CO-SR' '', in which R '' 'is as defined above; CONR '' 'R °, in which R' '' is as defined above and R ° is hydrogen or is as defined above for R '' ', or R' '' and R °, together with nitrogen a which they join, forming a group selected from the pyrrolidino, piperidino and morpholino groups, a group S02NR '' 'R °, in which R' '' is as defined above and R ° is hydrogen or is as defined previously for R '' ', or R' '' and R °, together with nitrogen to which they are bound, forming a group selected from the pyrrolidino, piperidino and morpholino groups, - R "is hydrogen, a halogen, an alkyl of 1 to 6 carbon atoms, a functional group as defined above, a group OR '' ', R' '' being as defined above, a group COOR '' ' , R '' 'being as defined above, or a group CONR' '' R °, in which R '' 'is as defined above and R ° is hydrogen or is as defined above for R' '', or R '' 'and R °, together with the nitrogen to which they are bound, forming a group selected from the pyrrolidino, piperidino and morpholino groups, - W is a direct bond or an oxygen atom; - X 'is hydrogen, an alkyl of 1 to 6 carbon atoms or an alkylcarbonyl of 1 to 6 carbon atoms; - Y is hydrogen or a group A '-CH (OH) -CH2-, A' is identical to A but other than benzofuran-2-yl; or - X 'and Y, taken together, form a methylene group optionally substituted by an alkoxycarbonyl in which the alkoxy is from 1 to 6 carbon atoms; an ethylene group optionally substituted by an oxo group; or a 1,3-propylene group; - Z is a hydrogen or an alkyl of 1 to 6 carbon atoms, or a pharmaceutically acceptable salt thereof 25. A pharmaceutical composition according to any of claims 20 to 22, characterized in that the β3 agonist is a compound of the formula wherein - E is hydrogen, an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a phenyl, a nitro, a halogen atom or a trifluoromethyl; - L is hydrogen, an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a phenyl, a nitro or a halogen atom; or E and L together are a group -CH = CH-CH = CH- or -CH2-CH2-CH2-CH2-; and - G is hydrogen, a chlorine atom, a hydroxyl or an OG 'group, in which G' is an alkyl of 1 to 4 carbon atoms which is unsubstituted or substituted by a hydroxyl, alkoxy of 1 to 4 atoms carbon, alkoxycarbonyl of 1 to 4 carbon atoms, cycloalkylcarboxyl of 3 to 7 carbon atoms; a cycloalkyl of 3 to 7 carbon atoms; or an alkanoyl of 2 to 4 carbon atoms, or one of its pharmaceutically acceptable salts, 26. The use according to claim 23, characterized in that the β3 receptor antagonist is N- [(2S) -7-ethoxycarbonylmethoxy-1,2,3,4-tetrahydronaphth-2-yl] - (2R) -2- ( 3-chlorophenyl) -2-hydroxyethamine or one of its pharmaceutically acceptable salts. 27. A pharmaceutical composition according to any of claims 20 to 26, characterized in that it contains from 0.5 to 600 mg of CBi receptor antagonist and from 0.5 to 600 mg of the β3 agonist. 28. A pharmaceutical composition according to claim 27, characterized in that it contains from 1 to 400 mg of CBi receptor antagonist and from 2 to 400 mg of the β agonist. 29. A pharmaceutical composition according to claim 28, characterized in that it contains from 2 to 200 mg of CBi receptor antagonist and from 10 to 250 mg of the β3 agonist. 30. A team for the treatment of appetite disorders, characterized because it contains: - a CBi receptor antagonist, and - a regulator of metabolic disorders, said active principles are in separate compartments and designated to be administered simultaneously, sequentially or over a period of time. 31. A device according to claim 30, characterized in that said regulator of metabolic disorders is a β3 agonist. 32. An equipment according to claim 30 or 31, characterized in that said CBi receptor antagonist is N-piperidino-5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methylpyrazolo-3-carboxamide, a of its pharmaceutically acceptable salts or one of its solvates and the β3 agonist is N- [(2S) -7-ethoxycarbonylmethoxy-1,2,3,4-tetrahydronaphth-2-yl] - (2R) -2- (3- chlorophenyl) -2-hydroxyethamine or one of its pharmaceutically acceptable salts. 33. A device according to any of claims 30 to 32, characterized in that said active ingredients are in different packages. 34. The use according to claim 1, characterized by the preparation of a drug useful for regulating the desired consumption by non-essential elements of the diet 35. The use according to claim 1, characterized in that the non-essential elements of the diet are excess sugars, excess carbohydrates, alcohol and drugs. 36. The use of a CBX receptor antagonist characterized for the preparation of a medicament useful for suppressing the spontaneous appetite for a food that usually provides a pleasure. 37. The use according to claim 36, characterized in that the food that provides a pleasure is alcohol or sugar. 38. The use according to any of claims 34 to 37 characterized, because the CBi receptor antagonist is N-pipéridino-5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methylpyrazolo-3-carboxamide , one of its pharmaceutically acceptable salts or one of its solvates.