[go: up one dir, main page]

WO2008035177A2 - Combinaison d'agonistes du récepteur de la mélatonine mt1 et mt2 avec un inhibiteur de la recapture de la norépinephrine/dopamine - Google Patents

Combinaison d'agonistes du récepteur de la mélatonine mt1 et mt2 avec un inhibiteur de la recapture de la norépinephrine/dopamine Download PDF

Info

Publication number
WO2008035177A2
WO2008035177A2 PCT/IB2007/002712 IB2007002712W WO2008035177A2 WO 2008035177 A2 WO2008035177 A2 WO 2008035177A2 IB 2007002712 W IB2007002712 W IB 2007002712W WO 2008035177 A2 WO2008035177 A2 WO 2008035177A2
Authority
WO
WIPO (PCT)
Prior art keywords
bupropion
disorders
agomelatine
melatonin receptor
norepinephrine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2007/002712
Other languages
English (en)
Other versions
WO2008035177A3 (fr
Inventor
Guy Jadot
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Copharm
Original Assignee
Copharm
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Copharm filed Critical Copharm
Publication of WO2008035177A2 publication Critical patent/WO2008035177A2/fr
Publication of WO2008035177A3 publication Critical patent/WO2008035177A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants

Definitions

  • the present invention relates to the use of a combination of a MT1/MT2 melatonin receptor and a norepinephrine/ dopamine reuptake inhibitor for the treatment of CNS disorders.
  • Agomelatine is known to be well tolerated, have a favourable safety profile and to induce little sexual dysfunction.
  • Clinical studies on depression indicate that the non-response to agomelatine is similar to the selective serotonin reuptake inhibitors (SSRIs), were non response is in the range of 30%.
  • SSRIs have become first choice therapeutics in the treatment of depression, certain forms of anxiety and social phobias but suffer from a number of side effects, among them sexual dysfunction.
  • Antidepressants in general demonstrate a delay in the therapeutic effect of up to 4 weeks.
  • Augmentation of antidepressant therapy may be accomplished through the coadministration of mood stabilizers such as lithium carbonate or triiodothyronin or by the use of electroshock.
  • mood stabilizers such as lithium carbonate or triiodothyronin
  • electroshock There is also a need for an antidepressant treatment that shortens the onset of action.
  • bupropion or its metabolites including radafaxine, or pharmaceutically acceptable salt, solvate, clathrate, polymorph or co-crystal thereof may be used to augment and also provide faster onset of the therapeutic effect of agomelatine in a synergistic way.
  • the present invention thus provides:
  • the present invention relates to the use of bupropion, or any other NDRI, or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition to be used in combination with agomelatine or any other MTl and MT2 melatonin receptor agonists with any pharmaceutically acceptable salt, solvate, clathrate, polymorph or co-crystal of the compounds .
  • the present invention relates to the use of bupropion, or its metabolites including radafaxine or any other NDRI, or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition useful for augmenting and/or providing faster onset of the therapeutic effect of agomelatine or any other MTl and MT2 melatonin receptor agonists in a synergistic way.
  • the present invention relates to the use as above, of bupropion, or a pharmaceutically acceptable salt thereof, for the treatment of depression, recurrent depression, resistant depression, bipolar disorders, anxiety disorders and other affective disorders, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders, sleep disorders, stress-related disorders, attention deficit hyperactivity disorder and drug abuse, in particular depression with agomelatine or any other MTl and MT2 melatonin receptor agonists.
  • the anxiety disorders mentioned above include, but are not limited to, general anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post trauma stress disorder or social anxiety disorder.
  • augmenting covers improving the therapeutic effect and/or potentiating the therapeutic effect of agomelatine or any other MTl and MT2 melatonin receptor agonists in a synergistic way.
  • the invention relates to the use of bupropion or a pharmaceutically acceptable salt thereof and a compound, which is agomelatine, or any other MTl and MT2 melatonin receptor agonists, for the preparation of a pharmaceutical composition or kit for' the treatment of diseases or disorders responsive to the therapeutic effect of agomelatine, or any other MTl and MT2 melatonin receptor agonists .
  • the diseases responsive to agomelatine, or any other MTl and MT2 melatonin receptor agonists include, but are not limited to, depression, bipolar disorders, anxiety disorders and other affective disorders, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders, attention deficit hyperactivity disorder and drug abuse, in particular depression.
  • anxiety disorders is as defined above.
  • the present invention relates to the use of bupropion, or its metabolites including radafaxine or a pharmaceutically acceptable salt thereof, for the preparation of a pharmaceutical composition as above, which is adapted for simultaneous administration of the active ingredients.
  • a pharmaceutical composition as above, which is adapted for simultaneous administration of the active ingredients.
  • such pharmaceutical compositions may contain the active ingredients within the same unit dosage form, e.g. in the same tablet or capsule.
  • Such unit dosage forms may contain the active ingredients as a homogenous mixture or in separate compartments of the unit dosage form.
  • the present invention relates to the use of bupropion or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition or kit as above, which is adapted for sequential administration of the active ingredients.
  • such pharmaceutical compositions may contain the active ingredients in discrete unit dosage forms, e. g. discrete tablets or capsules containing either of the active ingredients. These discrete unit dosage forms may be contained in the same container or package, e.g. a blister pack.
  • kit means a pharmaceutical composition containing each of the active ingredients, but in discrete unit dosage forms.
  • the invention also relates to a pharmaceutical composition or kit comprising bupropion or a pharmaceutically acceptable salt thereof and a compound, which is agomelatine, or any other MTl and MT2 melatonin receptor agonists, and optionally pharmaceutically acceptable carriers or diluents.
  • composition or kit of the invention may be adapted for simultaneous administration of the active ingredients or for sequential administration of the active ingredients, as described above.
  • the present invention relates to a method for the treatment of diseases or disorders responsive to agomelatine, or any other MTl and MT2 melatonin receptor agonists, comprising administering bupropion or a pharmaceutically acceptable salt thereof and agomelatine, or any other MTl and MT2 melatonin receptor agonists, to an individual in need thereof.
  • the present invention relates to a method for augmenting and/or providing faster onset of the therapeutic effect of agomelatine, or any other MTl and MT2 melatonin receptor agonists, comprising administering bupropion or a pharmaceutically acceptable salt thereof to an individual to be treated with or undergoing treatment with agomelatine, or any other MTl and MT2 melatonin receptor agonists.
  • the individuals which may benefit from treatment with a combination as above, may suffer from depression, recurrent depression, resistant depression, bipolar disorders, anxiety disorders and other affective disorders, eating disorders such as bulimia, anorexia and obesity, phobias, premenstrual syndrome, dysthymia, cognitive disorders, impulse control disorders, attention deficit hyperactivity disorder and drug abuse, in particular depression.
  • anxiety disorder includes, but are not limited to, general anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post trauma stress disorder or social anxiety disorder.
  • Agomelatine and the norepinephrine/dopamine reuptake inhibitor may be administered simultaneously as described above.
  • the active ingredients may be administered sequentially, e.g. in two discrete unit dosage forms as described above.
  • Bupropion and pharmaceutically acceptable salts thereof claimed therein are described as blocking both norepinephrine and dopamine reuptake inhibitors.
  • bupropion is a selective norepinephrine and dopamine reuptake inhibitor with no serotonergic activity, common antidepressant-associated side effects, such as sexual dysfunction, weight gain, and sedation, are not associated with bupropion therapy.
  • the only other norepinephrine/dopamine reuptake inhibitor NDRI is radafaxine (GSK 353162) now in phase III.
  • Agomelatine as other antidepressants suffers from a delayed onset of action. Even in responders to agomelatine, several weeks of treatment are necessary to achieve a relief in symptoms. Bupropion may provide fast onset of the therapeutic effect of agomelatine.
  • the use of a combination of bupropion and agomelatine may provide a synergistic effect in the treatment of depression and other affective disorders compared to administration of agomelatine and bupropion alone while maintaining agomelatine' s favourable tolerance and safety profile, particularly absence of sexual dysfunction.
  • Co-administration of bupropion and agomelatine may also be useful for the treatment of refractory depression, i. e. depression, which cannot be treated appropriately by administration of agomelatine alone.
  • bupropion may be used as add-on therapy for the augmentation of the response to agomelatine in patients where at least 40-60% reduction in symptoms has not been achieved during the first 6 weeks of treatment with an SSRI.
  • Co-administration of bupropion and agomelatine may also be useful for the treatment of recurrent depression.
  • Any pharmacologically active compound which primarily or partly exerts its therapeutic effect via the MTl and MT2 melatonin receptor agonists pathway in the CNS, may benefit from augmentation with bupropion.
  • the following list contains a number of MTl and MT2 melatonin receptor agonists, which may benefit from augmentation with bupropion: agomelatine, ramelteon, TAK-375 (N, N, 6-trimethyl-2- (4-methylphenyl) - imidazo [1, 2-a] pyridine-3-acetamide) , VEC- 162, PD-6735, GR 196429, 5-Methoxy-N-cyclopropanoyltryptamine, 8M-PDOT (8-Methoxy-2-propionamidotetralin) , 2-phenylmelatonin, N-propionylmelatonin, N-butanoylmelatonin, 6-chloromelatonin.
  • the compounds mentioned above may be used in the form of the base or a pharmaceutically acceptable acid addition salt, solvate, clathrate, polymorph or co-crystal thereof thereof.
  • the active ingredients according to the invention i. e. bupropion and agomelatine or any other MTl and MT2 receptor agonists, may be used in the free base form (except agomelatine which is an amide) or in the form of a pharmaceutically acceptable acid addition salt thereof, the latter being obtainable by reaction of the base form with an appropriate acid.
  • combination therapy with bupropion and a normal dose of agomelatine has the advantage that an effective CNS effect may be obtained in the often large number of patients who do not respond to conventional monotherapy with agomelatine.
  • the amount of bupropion used in combination therapy may range from about 50 to about 1000mg/day, particularly from about 100 to about 600 mg/day and more particularly from about 150 to about 450 mg/day.
  • the amount of agomelatine used in combination therapy may range from 0.1 to about 300mg/day, particularly from about 1 to about 200 mg/day and more particularly from about 5 to lOOmg/day.
  • compositions of this invention an appropriate amount of the active ingredient (s) , in salt form or base form, is combined in an intimate admixture with a pharmaceutically acceptable carrier, which can take a wide variety of forms depending on the form of preparation desired for administration.
  • a pharmaceutically acceptable carrier which can take a wide variety of forms depending on the form of preparation desired for administration.
  • These pharmaceutical compositions are desirably in unitary dosage form suitable for administration orally, rectally, percutaneously or by parenteral injection.
  • any of the usual pharmaceutical media may be employed, such as, for example, water, glycols, oils, alcohols and the like in the case of oral liquid preparations such as suspensions, syrups, elixirs and solutions; or solid carriers such as starches, sugars, kaolin, lubricants, binders, disintegrating agents and the like in the case of powders, pills, capsules and tablets. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed.
  • unit dosage form refers to physically discrete units suitable as unitary dosages, each unit containing a predetermined quantity of active ingredient (s) calculated to produce the desired therapeutic effect, in association with the required pharmaceutical carrier.
  • dosage unit forms are tablets (including scored or coated tablets) , capsules, pills, powder packets, wafers, injectable solutions or suspensions, teaspoonfuls, tablespoonfuls and the like, and segregated multiples thereof.
  • Bupropion may be administered before, during or after the administration of agomelatine provided that the time between the administration of bupropion and agomelatine is such that ingredients are allowed to act synergistically on the CNS.
  • a composition containing both bupropion and agomelatine may be particularly convenient.
  • bupropion and agomelatine may be administered separately in the form of suitable compositions.
  • the present invention also comprises products containing bupropion and agomelatine as a combination preparation for simultaneous, separate or sequential use in psychiatric drug therapy.
  • Such products may comprise, for example, a kit comprising discrete unit dosage forms containing bupropion and discrete unit dosage forms containing agomelatine, all contained in the same container or pack, e.g. a blister pack.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne l'utilisation d'une combinaison d'agonistes du récepteur de la mélatonine MT1 et MT2 avec un inhibiteur de la recapture de la norépinephrine/dopamine (NDRI) destinée au traitement de la dépression et d'autres troubles affectifs. Cette invention concerne spécifiquement l'utilisation d'une combinaison d'agomélatine et de bupropion destinée au traitement de la dépression et d'autre trouble affectifs.
PCT/IB2007/002712 2006-09-18 2007-09-13 Combinaison d'agonistes du récepteur de la mélatonine mt1 et mt2 avec un inhibiteur de la recapture de la norépinephrine/dopamine Ceased WO2008035177A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US84520106P 2006-09-18 2006-09-18
US60/845,201 2006-09-18

Publications (2)

Publication Number Publication Date
WO2008035177A2 true WO2008035177A2 (fr) 2008-03-27
WO2008035177A3 WO2008035177A3 (fr) 2008-08-07

Family

ID=39200893

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2007/002712 Ceased WO2008035177A2 (fr) 2006-09-18 2007-09-13 Combinaison d'agonistes du récepteur de la mélatonine mt1 et mt2 avec un inhibiteur de la recapture de la norépinephrine/dopamine

Country Status (1)

Country Link
WO (1) WO2008035177A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009096564A1 (fr) * 2008-01-31 2009-08-06 Takeda Pharmaceutical Company Limited Agent prophylactique ou thérapeutique pour le trouble du déficit de l'attention avec hyperactivité
FR2956031A1 (fr) * 2010-02-11 2011-08-12 Servier Lab Utilisation de l'agomelatine pour l'obtention de medicaments destines au traitement du trouble obsessionnel compulsif (toc)
EP2517700A1 (fr) * 2011-04-28 2012-10-31 Zentiva, k.s. Cocristaux pharmaceutiquement acceptables de la N-[2-(7-méthoxy-1-naphthyl)éthyl]acetamide et méthodes de leur préparation
MD4308C1 (ro) * 2011-06-09 2015-05-31 Les Laboratoires Servier Cocristale noi ale agomelatinei, procedeu de obţinere a lor şi compoziţii farmaceutice care le conţin

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6562858B2 (en) * 1999-05-17 2003-05-13 St. Elizabeth's Medical Center Of Boston, Inc. Method for treating depression
US6239162B1 (en) * 1999-05-17 2001-05-29 St. Elizabeth's Medical Center Method for treating depression
AR047553A1 (es) * 2003-07-04 2006-01-25 Lundbeck & Co As H La combinacion de un inhibidor de reabsorcion de serotonina y agomelatina
CA2551637A1 (fr) * 2003-12-24 2005-07-14 Sepracor Inc. Polytherapie a base de melatonine destinee a ameliorer la qualite du sommeil

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009096564A1 (fr) * 2008-01-31 2009-08-06 Takeda Pharmaceutical Company Limited Agent prophylactique ou thérapeutique pour le trouble du déficit de l'attention avec hyperactivité
FR2956031A1 (fr) * 2010-02-11 2011-08-12 Servier Lab Utilisation de l'agomelatine pour l'obtention de medicaments destines au traitement du trouble obsessionnel compulsif (toc)
WO2011098689A3 (fr) * 2010-02-11 2011-12-08 Les Laboratoires Servier Utilisation de l'agomelatine pour l'obtention de medicaments destines au traitement du trouble obsessionnel compulsif (toc)
CN102781437A (zh) * 2010-02-11 2012-11-14 瑟维尔实验室 阿戈美拉汀在得到预定治疗强迫性障碍(ocd)的药物中的用途
AU2011214190B2 (en) * 2010-02-11 2013-04-18 Les Laboratoires Servier Use of agomelatine for the preparation of drugs for treating obsessive compulsive disorder (OCD)
JP2013519659A (ja) * 2010-02-11 2013-05-30 レ ラボラトワール セルヴィエ 強迫性障害（ｏｃｄ）処置用の薬剤の製造のためのアゴメラチンの使用
EA023473B1 (ru) * 2010-02-11 2016-06-30 Ле Лаборатуар Сервье Применение агомелатина для получения лекарственных средств, предназначенных для лечения обсессивно-компульсивного расстройства (окр)
EP2517700A1 (fr) * 2011-04-28 2012-10-31 Zentiva, k.s. Cocristaux pharmaceutiquement acceptables de la N-[2-(7-méthoxy-1-naphthyl)éthyl]acetamide et méthodes de leur préparation
WO2012146371A1 (fr) * 2011-04-28 2012-11-01 Zentiva, K.S. Co-cristaux de n-[2-(7-méthoxy-1-naphtyl)éthyl]acétamide pharmaceutiquement acceptables et leurs procédés de préparation
US8927771B2 (en) 2011-04-28 2015-01-06 Zentiva K.S. Pharmaceutically acceptable cocrystals of N-[2-(7-methoxyl-1-naphtyl)ethyl]acetamide and methods of their preparation
EA024422B1 (ru) * 2011-04-28 2016-09-30 Зентива, К.С. Фармацевтически приемлемые сокристаллы n-[2-(7-метокси-1-нафтил)этил]ацетамида и способы их получения
MD4308C1 (ro) * 2011-06-09 2015-05-31 Les Laboratoires Servier Cocristale noi ale agomelatinei, procedeu de obţinere a lor şi compoziţii farmaceutice care le conţin

Also Published As

Publication number Publication date
WO2008035177A3 (fr) 2008-08-07

Similar Documents

Publication Publication Date Title
US11793794B2 (en) Combination therapy for treating or preventing depression or other mood diseases
EP1643985B1 (fr) Combinaison d'un inhibiteur de recaptage de la serotonine et d'agomelatine
PL188520B1 (pl) Kombinacja farmaceutyczna, sposób wytwarzania leku i zestaw farmaceutyczny
US6169098B1 (en) Composition and methods employing it for the treatment of 5-HT-mediated disorders
EA003142B1 (ru) Лекарственное средство, обладающее антидепрессивным действием, его применение и способ лечения
KR20220097394A (ko) Gaba-a 수용체 양성 알로스테릭 조절제와 nmda 길항제, nmda 음성 알로스테릭 조절제, 또는 nmda 부분 작용제의 조합
WO2008035177A2 (fr) Combinaison d'agonistes du récepteur de la mélatonine mt1 et mt2 avec un inhibiteur de la recapture de la norépinephrine/dopamine
WO2004105690A2 (fr) Traitement de douleurs chroniques au moyen de chimiotherapie ou de radiotherapie
JPS6110509A (ja) 医薬組成物
KR20050049476A (ko) 홍조를 치료하기 위한 레복세틴의 용도
KR20080031937A (ko) 골수종 치료를 위한 ｈｄａｃ 저해제의 용도
US10576045B2 (en) Low dosage combinations of fluoxetine and reboxetine for treating obesity
MX2014012859A (es) Composicion farmaceutica que comprende (1r,4r)-6'-fluoro-n,n-dimet il-4-fenil-4',9'-dihidro-3'h-espiro[ciclohexan-1-1'-pirano[3,4,b] indol]-4-amina y antidepresivos.
WO2023154450A3 (fr) Polythérapie à base d'antagoniste du récepteur nmda-(ampa-pam) pour le traitement d'affections et de troubles mentaux
WO1998044924A1 (fr) Procede pour traiter la depression, les troubles obsessifs impulsifs ou l'anxiete
SK3272001A3 (en) A new composition
WO2024023278A1 (fr) Polythérapie anticancéreuse comprenant un inhibiteur de flt3
AU2004313648B2 (en) Combinations of serotonin reuptake inhibitors and imidazoline-I2-agonists
ES2361507T3 (es) La combinación de un inhibidor de reabsorción de la serotonina y agomelatina.
SK3262001A3 (en) A new composition
KR20140069120A (ko) S1p 수용체 조절제를 포함하는 조합물
Kapur Adjuvant and miscellaneous drugs used in pain management
HRP20100463A2 (hr) Upotreba čistog enantiomernog citaloprama
MXPA06004782A (es) Formulacion oral antidepresiva que comprende acido acetilsalicilico para acelerar la presentacion de la accion
HK1096872A (en) The combination of a serotonin reuptake inhibitors and agomelatine

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07804943

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07804943

Country of ref document: EP

Kind code of ref document: A2