MXPA00010435A - Paroxetine 10-camphorsulfonate for treatment of cns disorders - Google Patents
Paroxetine 10-camphorsulfonate for treatment of cns disordersInfo
- Publication number
- MXPA00010435A MXPA00010435A MXPA/A/2000/010435A MXPA00010435A MXPA00010435A MX PA00010435 A MXPA00010435 A MX PA00010435A MX PA00010435 A MXPA00010435 A MX PA00010435A MX PA00010435 A MXPA00010435 A MX PA00010435A
- Authority
- MX
- Mexico
- Prior art keywords
- paroxetine
- camphor sulfonate
- solution
- camphor
- salt
- Prior art date
Links
- 229960002296 paroxetine Drugs 0.000 title claims abstract description 27
- AHOUBRCZNHFOSL-YOEHRIQHSA-N Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 title claims description 28
- MIOPJNTWMNEORI-UHFFFAOYSA-M camphorsulfonate anion Chemical compound C1CC2(CS([O-])(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-M 0.000 title claims description 12
- 201000010099 disease Diseases 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000012458 free base Substances 0.000 claims description 8
- 201000008430 obsessive-compulsive disease Diseases 0.000 claims description 5
- 239000003921 oil Substances 0.000 claims description 5
- MIOPJNTWMNEORI-UHFFFAOYSA-N Camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims description 4
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000005712 crystallization Effects 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 208000007848 Alcoholism Diseases 0.000 claims description 2
- 206010001897 Alzheimer's disease Diseases 0.000 claims description 2
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
- 208000000094 Chronic Pain Diseases 0.000 claims description 2
- 206010061428 Decreased appetite Diseases 0.000 claims description 2
- 206010013982 Dysthymic disease Diseases 0.000 claims description 2
- 206010027599 Migraine Diseases 0.000 claims description 2
- 208000008085 Migraine Disorders Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 206010033666 Panic disease Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 206010041250 Social phobia Diseases 0.000 claims description 2
- 208000002271 Trichotillomania Diseases 0.000 claims description 2
- 201000007930 alcohol dependence Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- 230000004927 fusion Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims description 2
- 238000007711 solidification Methods 0.000 claims description 2
- 238000001694 spray drying Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 206010002855 Anxiety Diseases 0.000 claims 1
- 206010057666 Anxiety disease Diseases 0.000 claims 1
- 230000036506 anxiety Effects 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- -1 Paroxetine 10-camphorsulfonates Chemical class 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 150000003839 salts Chemical class 0.000 description 17
- 239000011780 sodium chloride Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- MIOPJNTWMNEORI-XVKPBYJWSA-N (R)-camphorsulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)C[C@H]1C2(C)C MIOPJNTWMNEORI-XVKPBYJWSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium phosphate dihydrate Substances O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4S)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005755 formation reaction Methods 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 206010012378 Depression Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- PYHRZPFZZDCOPH-QXGOIDDHSA-N (S)-amphetamine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C[C@H](N)CC1=CC=CC=C1.C[C@H](N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-QXGOIDDHSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- 229920003084 Avicel® PH-102 Polymers 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butanoic acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 210000003169 Central Nervous System Anatomy 0.000 description 1
- 108060009526 FEN1 Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000007656 Osteochondritis Dissecans Diseases 0.000 description 1
- 230000001430 anti-depressive Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000001483 mobilizing Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylaxis Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Abstract
Paroxetine 10-camphorsulfonates are useful in the treatment of certain CNS disorders.
Description
-ALCANF? PARQXETINE RSULFQNATO FOR TREATMENT OF DISORDERS OF THE CENTRAL NERVOUS SYSTEM
DESCRIPTIVE MEMORY
The present invention relates to a new compound, to processes for preparing it and to its use in the treatment of medical disorders. Pharmaceutical products with antidepressant and antiParkinson properties are described in US-A-3912743 and US-A-4007196. An especially important compound among those described is paroxetine, the (-) trans isomer of 4- (4'-fluorophenyl) -3- (3 ', 4, -methylenedioxy-phenoxymethyl) piperidine. This compound is used in therapy as a hydrochloride salt for the treatment and prophylaxis of, among other conditions, depression, obsessive-compulsive disorder (OCD, for its acronym in English) and panic. Surprisingly, a new paroxetine salt has now been discovered that can be used as an alternative to the hydrochloride currently marketed, or as an intermediate in the preparation of the hydrochloride. In accordance with this invention, a paroxetine camphor-10-sulfonate is provided. 10-Camphor sulfonic acid exists in enantiomeric forms and this invention includes salts with both D - (+) - 10- acid
camphorsulfonic as with (1 R) - (-) - 10-camphorsulfonic acid, as well as racemic mixtures of both salts. In one aspect, the novel salt of this invention is provided in non-crystalline form, which may be a solid or an oil. The oil is preferably absorbed in a solid carrier, especially a vehicle that is usable as a component of a pharmaceutical composition. In another aspect, the new salt of this invention is provided in crystalline form. When the crystalline form exists as more than one polymorph, each polymorph forms another aspect of this invention. Paroxetine camphor-10-sulfonate can be prepared by contacting stoichiometric amounts of the paroxetine free base and acid. It is preferred that the acid or base be in solution; more preferably, that both are in solution. An elevated temperature can be used to bring the acid to solution, but good salt yields are obtained by evaporating some or all of the solvents, or by controlled cooling, preferably in stages. The most commonly used solvents are suitable for mobilizing the paroxetine free base; for example, toluene, alcohols such as methanol, ethanol, propan-2-ol; esters such as ethyl acetate; ketones such as acetone and butanone; halogenated hydrocarbons such as dichloromethane, and ethers such as diethyl ether and tetrahydrofuran ether, but the solvents in which camphor-10-sulphonic acids are highly insoluble are preferably avoided. The appropriate solvents for acids
Camphor-10-sulfonic acids include water, alcohols, ethyl acetate and acetic acid. The salt can be isolated in solid form by common means of a solution thereof obtained as mentioned above. For example, the non-crystalline salt can be prepared by precipitation, spray drying and lyophilization of solutions, or by vacuum drying oils or solidification of fusions obtained from the reaction of the free base and the acid. The crystalline salt can be prepared by crystallization or recrystallization from appropriate solvents. When the salt is obtained as a solvate, by association with the solvent in which it is dissolved, said solvate constitutes an additional aspect of this invention. The solvates can be returned to the unsolvated salt by heating; for example, by drying in the oven, or by treatment with a displacement solvent that does not form a solvate. Before the isolation of the paroxetine salt, the water can be extracted by azeotropic distillation to avoid the formation of hydrates or obtain the product in anhydrous form. In that case, the appropriate solvents for the salt solution are those that form an azeotrope with water, such as toluene and propan-2-ol. Also, it should be noted that the mixtures of the solvents can also be used to assist the azeotropic extraction of the water. More generally, crystallization can be carried out from any solvent that allows the formation of the crystalline structure
desired, using seeds of the desired structure where necessary or desirable. When polymorphs exist, the individual polymorphs are preferably directly crystallized from a solution of the salt, although recrystallization of a polymorph solution using seeds from another polymorph can also be performed. The paroxetine free base can be prepared according to the methods generally described in the US patent. no.
No. 4,007,196 and in European patent EP-B-0 223403. D-10-camphor sulfonic acid and L-10-alconforsulfonic acid are commercially available. The compounds of this invention can be used to treat and prevent the following disorders:
Alcoholism Anxiety Depression Obsessive-compulsive disorder Panic disorder Chronic pain Obesity Senile dementia Migraine Bulimia Anorexia Social phobia Premenstrual syndrome Depression in adolescents (PMS) Dysthymia Trichotillomania Excessive use of substances
In the following, these disorders are referred to as 'disorders'.
The present invention also provides a method for treating and / or preventing one or more of the disorders by administering an effective and / or prophylactic amount of a salt of the invention to the patient in need thereof. The present invention further provides a pharmaceutical composition that is used to treat and / or prevent disorders, which consists of a mixture of a salt of the invention with a pharmaceutically acceptable carrier. The present invention also provides the use of a salt of the invention to treat and / or prevent disorders. The present invention also provides the use of a salt of the invention in the manufacture of a medicament for treating and / or preventing disorders. More appropriately, this invention is applied to the treatment of depression, obsessive-compulsive disorder and panic. The compositions of this invention are generally adapted for oral administration, but formulations for dissolution for parenteral administration also fall within the scope of this invention. The composition is generally presented as a unit dose composition containing from 1 to 200 mg of active ingredient calculated based on a free base, more often from 5 to 100 mg; for example, from 10 to 50 mg, such as 10, 12.5, 15, 20, 25, 30 040 mg per human patient. More preferably, single unit doses contain 20 mg of active ingredient calculated based on a free base.
Said composition is usually taken 1 to 6 times a day; for example, 2, 3 or 4 times a day, such that the total amount of active agent administered falls on the scale of 5 to 400 mg of active ingredient calculated based on free base. More preferably, the dose of a unit is taken once a day. Preferred dosage forms of a unit include tablets or capsules. The compositions of this invention can be formulated by common mixing methods, such as mixing, filling and compression. Suitable vehicles for use in this invention comprise a diluent, a binder, a disintegrant, a coloring agent, a flavoring agent and / or a preservative. These agents can be used in a common way; for example, in a manner similar to that already used for commercial antidepressant agents. Specific examples of pharmaceutical compositions include those described in European Patent EP-B-0-223403, and in that of US Pat. No. 4,007,196, in which the products of this invention can be used as active ingredients. The following examples illustrate this invention:
EXAMPLE 1 Preparation of crystalline paroxetine D - (+) - 10-camphor sulfonate
A solution of paroxetine base in toluene (5 ml, 6.38 mmol) was added to a solution of D (+) - 10-camphorsulfonic acid (1.48 g,
6 38 mmol) in methanol (20 ml). The mixture was allowed to stand at room temperature for 20 minutes and the solvent was removed in vacuo. The residue was diluted with toluene (20 ml) and the solvent was removed in vacuo. Trituration with diethyl ether (c.50 ml) and filtration under nitrogen gave a white solid, which was washed with diethyl ether (2 x 20 ml) and dried in a desiccator in vacuo. Yield: 3.50 g.
EXAMPLE 2 Preparation on a larger scale of the crystalline salt
A solution of paroxetine base in toluene (75 ml, 95.7 mmol) was added to a solution of D (+) - 10-camphorsulfonic acid (22.2 g, 95.7 mmol) in methanol (300 ml). The solvent was removed in vacuo, the residue was diluted with toluene (100 ml) and the solvent was removed in vacuo. Trituration with diethyl ether (c 350 ml) gave a white solid which was filtered, washed with diethyl ether (2 x 100 ml) and dried in vacuo. Yield: 54.46 g
The 1 H NMR resonance (CDCl 3) showed a ratio of 1: 1 between D (+) - 10-camphor sulfonic acid and paroxetine. p.f. 109 ° C (phase change). Nujol mordente for IR: Bands in 1740, 1501, 1464, 1376, 1183, 1034, 828, 768, 601,
515 cm "1. Greater peaks of the X-ray diffractogram (CuK2a):
EXAMPLE 3 Preparation of crystalline paroxetine (1 RM -) - 10-camphor sulfonate
A solution of paroxetine base in toluene (5 ml, 6.38 mmol) was added to a solution of (1 R) - (-) - 10-camphorsulfonic acid (1.48 g, 6.38 mmol) in methanol (20 ml). The mixture was allowed to stand at room temperature for 20 minutes and then the solvent was removed in vacuo. The residual solid was diluted with toluene (20 ml) and the solvent was removed in vacuo. Trituration with diethyl ether (c.50 ml) and filtration under nitrogen gave a white solid which was washed with diethyl ether (2 x 20 ml) and dried under reduced pressure. Yield: 3.18 g.
EXAMPLE 4 Preparation on a larger scale of the crystalline salt
A solution of paroxetine base in toluene (66 ml, 84.16 mmol) was added to a solution of (1 R) - (-) - 10-camphorsulfonic acid (19.5 g, 83.94 mmol) in methanol (200 ml). The mixture was allowed to stand at room temperature for 40 minutes and then the solvent was removed by evaporation. The residual solid was triturated with diethyl ether (0. 350 ml), stirred at room temperature for 16 hours and filtered to give a white solid which was washed with diethyl ether (2 x 100 ml) and dried under reduced pressure.
Yield: 43.77g. The 1 H NMR magnetic resonance (CDCI) showed a 1: 1 ratio between (1 R) - (-) - 10-camphor sulfonic acid and paroxetine. p.f. 136-139 ° C. IR mordant of nujol: Bands in 1736, 1604, 1503, 1462, 1376, 1278, 1194, 1037, 827, 670, 602, 538 crn 1. Greater peaks of the X-ray diffractogram (CuK2a):
EXAMPLE 5 Preparation of tablets
Commercial origin of the ingredients Dicalcium phosphate dihydrate - Emcompress or Ditab * Microcrystalline cellulose - Avicel PH 102 * Sodium starch glycolate - Explotab * * Trade names.
Method 1. Pass DCP through the sieve and weigh it in a planetary mixer.
2. Add 30 mesh paroxetine 10-camphor sulfonate to the bowl.
3. Add Avicel and Explotab of 20 mesh and mix all the powders for 10 minutes. 4. Add magnesium stearate and mix for 5 minutes.
Formation of pentagonal tablets using the following dies: 30 mg tablet 9.5 mm Circumscribed circle 20 mg tablet 8.25 mm Circumscribed circle
The tablets were successfully processed in a single die or rotary press.
EXAMPLE 6 Preparation of tablets
Method 1. Paroxetine 10-camphorsulfonate, sodium starch glycolate and dicalcium phosphate dihydrate are sieved and mixed together in an appropriate mixer (planetary, Cuble mixer or high energy shear mixer). 2. Magnesium stearate is added and compressed into a tablet using a single die or rotary tablet machine.
Claims (9)
1. - A paroxetine 10-camphor sulfonate. 2.- (D) - (+) - 10-camphor sulfonate paroxetine. 3.- (1 R) - (-) - 10-camphor sulfonate paroxetine. 4. A compound according to claim 1, 2 6 3 in non-crystalline form. 5. A compound according to claim 1, 2 or 3 in crystalline form. 6. A process for preparing a compound according to claim 1, 2, 3 or 4, by precipitation, spray drying or lyophilization of a paroxetine 10-camphor sulfonate solution, or by vacuum drying oils of 10- paroxetine camphor sulfonate, or solidification of melted materials of paroxetine 10-camphorsulfonate. 7. A process for preparing compounds according to claim 1, 2, 3 or 5, by crystallization or recrystallization of a solution of paroxetine 10-camphor sulfonate. 8. A process according to claim 6 or 7, wherein the solution, oil or fusion of a paroxetine 10-camphor sulfonate is prepared by treating the paroxetine free base with 10-camphor sulfonic acid. 9. The use of a paroxetine 10-camphor sulfonate for the manufacture of a medicament to treat and / or prevent alcoholism, depression, panic disorder, obesity, migraine, anorexia, premenstrual syndrome (PMS), trichotillomania, excessive use of substances , anxiety, obsessive-compulsive disorder, chronic pain, senile dementia, bulimia, social phobia, depression in adolescents and dysthymia.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9808894.1 | 1998-04-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA00010435A true MXPA00010435A (en) | 2001-07-31 |
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