[go: up one dir, main page]

WO1996012485A1 - Traitement de troubles au moyen de la duloxetine - Google Patents

Traitement de troubles au moyen de la duloxetine Download PDF

Info

Publication number
WO1996012485A1
WO1996012485A1 PCT/US1995/013289 US9513289W WO9612485A1 WO 1996012485 A1 WO1996012485 A1 WO 1996012485A1 US 9513289 W US9513289 W US 9513289W WO 9612485 A1 WO9612485 A1 WO 9612485A1
Authority
WO
WIPO (PCT)
Prior art keywords
disorder
dependence
abuse
duloxetine
patient
Prior art date
Application number
PCT/US1995/013289
Other languages
English (en)
Inventor
John Harrison Heiligenstein
Gary Dennis Tollefson
David Taiwai Wong
Original Assignee
Eli Lilly And Company
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 Eli Lilly And Company filed Critical Eli Lilly And Company
Priority to AU41312/96A priority Critical patent/AU4131296A/en
Publication of WO1996012485A1 publication Critical patent/WO1996012485A1/fr

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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings

Definitions

  • the present invention belongs to the fields of medicine, psychiatric medicine and pharmaceutical chemistry, and provides several new methods of treating disorders by the administration of duloxetine.
  • Duloxetine inhibits the reupta e of both serotonin and norepinephrine, and is now in clinical trials as an antidepressant drug, and also for the treatment of urinary incontinence.
  • the present invention provides the use of duloxetine for a number of additional important purposes.
  • the present invention provides a method of treating or preventing a disorder in a patient having or at a heightened risk of contracting the disorder, comprising administering to the patient an effective amount of duloxetine, wherein the disorder is one of those explained below in detail.
  • Duloxetine is N-methyl-3- (1-naphthalenyloxy) -3- (2- thienyDpropanamine. It is usually administered as the ⁇ +) enantiomer, and as the hydrochloride salt. It was first taught by U.S. Patent 4,956,388, which teaches the synthesis of the compound as well as its high potency as an uptake inhibitor of both serotonin and norepinephrine. The word “duloxetine” will be used here to refer to any acid addition salt or the free base of the molecule, as well as to either an enantiomer or the racemate. It is to be understood, however, that the (+) enantiomer is preferred.
  • duloxetine for the treatment of a given patient with any particular disorder will vary, depending on the characteristics of the patient, as all clinicians and medical doctors are aware. Factors such as other diseases from which the patient suffers, the patient's age and size, and other medications which the patient may be using will have an effect on the duloxetine dose and will be taken into account. In general, however, the daily dose of duloxetine is from about 1 to about 80 mg. A more preferred dose range is from about 5 to about 40 mg, and another preferred range is from about 5 to about 20 mg, administered once daily.
  • Duloxetine is orally available and presently is orally administered, in the form of a tablet or a capsule full of enteric coated granules. Oral administration in such forms is preferred in the practice of the present invention. However, other routes of administration are also practical and may be preferred in certain cases. For example, transdermal administration may be very desirable for patients who are forgetful or petulant about taking oral medicine.
  • Sustained release formulations oral or percutaneous, may be prepared, but are not preferred because duloxetine is quite effective when administered once daily and there is little benefit from the additional effort of preparing the sustained action product.
  • duloxetine for use in the present invention follows the methods used in formulating duloxetine for other purposes, and indeed methods usual in pharmaceutical science are appropriate.
  • a preferred formulation of duloxetine comprises enteric pellets, or granules, of which a number are charged in a gelatin capsule.
  • the preferred duloxetine enteric formulation comprises a) a core consisting of duloxetine and a pharmaceutically acceptable excipient; b) an optional separating layer; c) an enteric layer comprising hydroxypropylmethylcellulose acetate succinate (HPMCAS) and a pharmaceutically acceptable excipient; d) an optional finishing layer.
  • HPMCAS hydroxypropylmethylcellulose acetate succinate
  • the duloxetine layer was built up by suspending duloxetine in a 4% w/w solution of the hydroxypropylmethyl ⁇ cellulose in water, and milling the suspension with a CoBall Mill (Fryma Mashinen AG, Rheinfelden, Switzerland) model MS- 12. A fluid bed dryer with a Wurster column was used to make this product, at a batch size of 1.0 kg. The separating layer was added from a 4% w/w solution of the hydroxypropyl ⁇ methylcellulose in water, in which the sucrose was also dissolved.
  • the enteric coating suspension In order to prepare the enteric coating suspension, purified water was cooled to 10°C and the polysorbate, triethyl citrate and silicone emulsion were added and dispersed or dissolved. Then the HPMCAS and talc were added and agitated until homogeneity was obtained, and the HPMCAS was fully neutralized by addition of ammonium hydroxide until solution of the polymer was complete. To this suspension, a carboxymethylcellulose aqueous solution, 0.5% w/w, was added and blended thoroughly. The enteric suspension was maintained at 20°C during the coating process. The enteric suspension was then added to the partially completed pellets in the Wurster column at a spray rate of about 15 ml/min, holding the temperature of the inlet air at about 50°C.
  • the product was dried in the Wurster at 50°C when the enteric suspension had been fully added, and then dried on trays for 3 hours in a dry house at 60°C.
  • a finishing layer was then applied which consisted of a 4.5% w/w/ hydroxypropylmethyl ⁇ cellulose solution containing titanium dioxide and propylene glycol as plasticizer.
  • the pellets were completely dried in the fluid bed dryer and then were then filled in size 3 gelatin capsules.
  • the patient to be benefited by practice of the present invention is a patient having one or more of the disorders discussed in detail below, or who is at a heightened risk of contracting such disorder. Diagnosis of these disorders, or the identification of a patient at risk of one or more of them, is to be made by a physician or psychiatrist.
  • duloxetine's potency in inhibiting the uptake of serotonin and norepinephrine is the mechanism by which it benefits such patients, by alleviating the effects of the disorder from which the patient suffers, or even eliminating the disorder completely.
  • a patient with a heightened risk of contracting one of the present disorders is a patient, in the present contemplation, who is more likely than is a normal person to fall victim to that disorder.
  • the patient may have suffered from the disorder in the past, and be at risk of a relapse, or may exhibit symptoms which demonstrate to the physician or psychiatrist that the patient is under an abnormal risk of developing the disorder in its full form.
  • DSM 307.51 is characterized , by uncontrollable binge eating, followed by self-induced purging, usually vomiting. Its prevalence is as high as 1%- 3% among adolescent and young adult females.
  • the disorder is well characterized and recognized by the health professions. The essential features of it are binge eating and inappropriate compensatory methods to prevent weight gain. Further, individuals with the disorder are excessively influenced by body shape and weight.
  • Obsessive-compulsive disorder DSM 300.3
  • DSM 300.3 is characterized by recurrent obsessions or compulsions which are severe enough to be time consuming or cause distress or impairment of the patient's life.
  • Obsessions are persistent ideas, thoughts, impulses or images which are recognized by the patient to be intrusive and inappropriate and cause anxiety or distress. The individual senses that the obsession is alien, not under control and not the kind of thought that the patient would expect to have.
  • Common obsessions include repeated thoughts about contamination, repeated doubts, a need to arrange things in a particular order, aggressive or undesirable impulses and sexual imagery.
  • Compulsions are repetitive behaviors, such as hand washing, or mental acts, such as counting or repeating words silently, the goal of which is to prevent or reduce anxiety or distress. By definition, compulsions are either clearly excessive or not realistically connected with that which they are designed to neutralize or prevent.
  • Obsessive-compulsive disorder is rather common, with an estimated lifetime prevalence of 2.5%.
  • Substance abuse and substance dependence come about when the patient becomes addicted or habituated to the improper use of a drug or other substance.
  • substance abuse or dependence often results in additional disorders, including intoxication, withdrawal symptoms, delirium, psychotic disorders, hallucinations, mood disorders, anxiety disorders, sexual dysfunctions, or sleep disorders.
  • Recognized substance abuse and substance dependence disorders which are part of the present invention include the following: amphetamine dependence, DSM 304.40 amphetamine abuse, DSM 305.70 cannabis dependence, DSM 304.30 cannabis abuse, DSM 305.20 cocaine dependence, DSM 304.20 cocaine abuse, DSM 305.60 hallucinogen dependence, DSM 304.50 hallucinogen abuse, DSM 305.30 inhalant dependence, DSM 304.60 inhalant abuse, DSM 305.90 nicotine dependence, DSM 305.10 opioid dependence, DSM 304.00 opioid abuse, DSM 305.50 phencyclidine dependence, DSM 304.90 phencyclidine abuse, DSM 305.90 sedative, hypnotic or anxiolytic dependence, DSM
  • DSM 304.10 sedative, hypnotic or anxiolytic abuse, DSM 305.40 polysubstance dependence, DSM 304.80
  • Panic attack, panic disorder and agoraphobia categorized as DSM 300.01, 300.21 and 300.22, affect between 1.5% and 3.5% of the population.
  • the disorders are characterized by irrational sense of imminent danger or doom, an urge to escape, or a fear of being in a situation from which escape might be difficult.
  • the patient exhibits symptoms such as palpitations, accelerated heart rate, sweating, sensations of shortness of breath, chest pain, nausea, dizziness, fear of dying, and the like, and may have such attacks very frequently.
  • DSM 300.23 produces a marked and persistent fear of social or performance situations in which embarrassment may occur. Exposure to such a situation may result in a panic attack, or other anxious response. Most often, patients with the disorder simply avoid situations of the type which they dread, producing an obvious dislocation in the patient's life. The prevalence of social phobia has been reported as from 3% to 13%, on a lifetime basis.
  • Post-traumatic stress disorder DSM 309.81, afflicts patients following exposure to a traumatic stress involving personal experience of an event involving actual or threatened death of injury.
  • Such traumatic events include experiences such as military combat, personal assault, kidnapping, terrorist attack, torture, natural or man-made disasters, severe accidents, or being diagnosed with a dreaded illness. Learning about such events occurring to others, particularly a family member or close friend, also may produce the disorder. Triggering events which symbolize the traumatic event, such as an anniversary, may recreate the stress and bring on the disorder long after the event is passed. Patients strive to avoid stimuli associated with the trauma, even to the point of amnesia or reduced responsiveness to other people in general. Prevalence of post-traumatic stress disorder has been reported at from 1% to as much as 14%, and has been reported at 50% and more in studies of individuals who are at risk of the disorder.
  • Dementia of the Alzheimer's type DSM 290.11, 290.12, 290.13, 290.10, 290.3, 290.20, 290.21 and 290.0, affects between 2% and 4% of the population over 65 years old. The prevalence increases with age, particularly after 75 years of age, and is associated with Alzheimer's disease. In most -9-
  • Attention deficit hyperactivity disorder DSM 314.01 and 314.00
  • DSM 314.01 and 314.00 Attention deficit hyperactivity disorder
  • DSM 314.01 and 314.00 is primarily recognized as a disorder of children, but may well be found in adults as well. It is characterized by symptoms such as lack of attention, impulsivity, and excessive activity, resulting in high expenditure of effort accompanied with a low degree of accomplishment. Patients have difficulty or find it impossible to give attention to details, cannot sustain attention in tasks or even play, and make careless mistakes. They fail to listen to or follow through on instructions, lose things, and are easily distracted by extraneous events. The difficulty of such patients in carrying out useful lives is obvious from the mere recital of the symptoms.
  • Disruptive behavior disorder is a condition characterized by aggressive, destructive, deceitful and defiant activity.
  • Intermittent explosive disorder DSM 312.34
  • DSM 312.34 Intermittent explosive disorder, DSM 312.34, is characterized by episodes of failure to resist aggressive impulses, resulting in assault or destruction of property.
  • the degree of aggressiveness expressed during episodes of this disorder is grossly disproportionate to any provocation or triggering stress.
  • the Southeastern Asian condition of amok is an episode of this disorder, cases of which have been reported in Canada and the United States as well.
  • Borderline personality disorder is marked by a pervasive pattern of instability of interpersonal relationships and self-image, and marked impulsivity which begins by early adulthood. Patients have a pattern of unstable and intense relationships, very quickly developing a very close relationship and then quickly devaluing the other person. Patients may gamble, spend irresponsibly, binge eat, abuse substances, engage in unsafe sex or drive recklessly. Patients often display recurrent suicidal behavior or self- injurious behavior. The prevalence is estimated to be about 2% of the population. Neuropathic pain, as distinct from other varieties of pain, emanates specifically from a neurologic source, as from a nerve which is unnaturally stressed, compressed or otherwise injured, it does not include pain emanating from an injury or inflammation of bone, muscle or other tissue.
  • Migraine is well-known as a headache, particularly a very severe headache, which occurs repetitively in patients subject to the condition. It has been treated with partial success with vasoconstrictors but no treatment of migraine in the prior art is reliably successful.
  • Premature ejaculation DSM 302.75, is characterized by the inability of a male to delay orgasm as long as is desired.
  • Depression and behavioral problems associated with head injury, mental retardation or stroke are treated in the exercise of the present invention. Such depression and behavioral problems are distinct from the usual such disorders, because of their origin. Depression, of course, of the general type is quite prevalent and is now well-known, being well treated with pharmaceuticals such as, for example, fluoxetine.
  • Chronic fatigue syndrome is a condition which has been variously described and diagnosed. It is sometimes categorized as a low-grade viral infection, particularly caused by the Epstein-Barr virus. Since that virus is very widely found in the population, however, the diagnosis is problematic.
  • An alternative characterization of chronic fatigue syndrome is a physical-psychological disorder of the depression type, characterized primarily by lack of energy and listlessness.
  • Premenstrual dysphoric disorder is characterized by symptoms such as feelings of sadness, hopelessness or self- deprecation; anxiety or tenseness; tearfulness and lability of mood; persistent irritability and anger; decreased interest in usual activities or withdrawal from relationships; difficulty concentrating and the like. It is not classified formally by DSM but is discussed in detail there. The pattern of symptoms occurs in most cycles, frequently beginning the week prior to menses. Frequently, the disorder markedly interferes with the patient's life in all respects during the attack of the disorder. The prevalence of the disorder in its most profound form has been estimated at 3%-5%, but there has been little systematic study on the course and stability of the condition.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La duloxétine est un principe actif convenant avantageusement à un procédé destiné à soulager plusieurs troubles, et notamment les troubles obsessionnels, la peur panique, les troubles de l'hyperactivité avec déficit de l'attention et la pharmacodépendance.
PCT/US1995/013289 1994-10-20 1995-10-18 Traitement de troubles au moyen de la duloxetine WO1996012485A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU41312/96A AU4131296A (en) 1994-10-20 1995-10-18 Treatment of disorders with duloxetine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US32663494A 1994-10-20 1994-10-20
US08/326,634 1994-10-20

Publications (1)

Publication Number Publication Date
WO1996012485A1 true WO1996012485A1 (fr) 1996-05-02

Family

ID=23273055

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/013289 WO1996012485A1 (fr) 1994-10-20 1995-10-18 Traitement de troubles au moyen de la duloxetine

Country Status (4)

Country Link
AU (1) AU4131296A (fr)
IL (1) IL115664A0 (fr)
WO (1) WO1996012485A1 (fr)
ZA (1) ZA958725B (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0721777A3 (fr) * 1995-01-11 1997-03-05 Lilly Co Eli Utilisation de tomoxetine pour le traitement de l'hyperactivité induite par les troubles d'attention
EP0919235A1 (fr) * 1997-09-23 1999-06-02 Eli Lilly And Company Utilisation d'un inhibiteur d'assimilation de norépinéphrine pour le traitement de trouble de la conduite
EP0919236A1 (fr) * 1997-09-23 1999-06-02 Eli Lilly And Company Utilisation d'un inhibiteur d'assimilation de norépinéphrine pour le traitement de trouble oppositionel provocant
EP0756869A3 (fr) * 1995-07-24 1999-06-16 Eli Lilly And Company Utilisation de la duloxétine ou de N-alkyl-3-phényl-(2-alkylthiophénoxy)-propylamines pour le traitement des troubles de l'attention et de l'hyperactivité
WO1999052531A1 (fr) * 1998-04-09 1999-10-21 Pharmacia & Upjohn Company Nouveaux traitements pour troubles nerveux
WO2000037073A1 (fr) * 1998-12-22 2000-06-29 Novartis Pharma Gmbh Utilisation d'antagonistes de recepteurs de 5ht3 aux fins de traitement du syndrome de fatigue chronique
EP1014971A4 (fr) * 1997-01-29 2000-07-05 Lilly Co Eli Traitement des troubles dysphoriques premenstruels
US6465458B1 (en) 1999-07-01 2002-10-15 Pharmacia & Upjohn Company Method of treating or preventing chronic pain with a highly selective norepinephrine reuptake inhibitor
WO2003011289A1 (fr) * 2001-07-31 2003-02-13 Pharmacia + Upjohn Company Traitement des douleurs chroniques au moyen de 3-heterocyclyl- et 3-cycloalkyl-3-aryloxypropanamines
US6586427B2 (en) 1998-04-09 2003-07-01 Pharmacia & Upjohn Company Treatments for nervous disorders
WO2003053426A1 (fr) * 2001-12-19 2003-07-03 Cypress Bioscience, Inc. Procedes pour traiter le syndrome de fibromyalgie, le syndrome de fatigue chronique et la douleur
US6596756B1 (en) 1998-09-15 2003-07-22 Eli Lilly And Company Treatment of fibromyalgia
US6630507B1 (en) 1998-04-21 2003-10-07 The United States Of America As Represented By The Department Of Health And Human Services Cannabinoids as antioxidants and neuroprotectants
WO2004019948A1 (fr) * 2002-08-29 2004-03-11 Arachnova Therapeutics Ltd. Nouvelles utilisations therapeutiques de la (4-(2-fluorophenyl)-6-methyl-2--(1-piperazinyl) thieno[2,3-d]pyrimidine
WO2004060366A1 (fr) * 2002-12-17 2004-07-22 Pharmacia Corporation Methode de traitement, de prevention ou d'inhibition d'un trouble du snc et/ou de la douleur et d'une inflammation, au moyen d'une combinaison de duloxetine, de venlafaxine ou d'atomoxetine et d'un inhibiteur selectif de la cyclo-oxygenase-2 et de ses compositions
EP1499309A4 (fr) * 2002-04-24 2008-05-28 Cypress Bioscience Inc Prevention et traitement de troubles somatiques fonctionnels, y-compris les troubles lies au stress
US7718705B1 (en) 1999-09-03 2010-05-18 Eli Lilly And Company Methods of using rapid-onset selective serotonin reuptake inhibitors for treating sexual dysfunction

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA93694B (en) * 1993-02-01 1993-06-03 Lilly Co Eli Pharmaceutical treatments.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA93694B (en) * 1993-02-01 1993-06-03 Lilly Co Eli Pharmaceutical treatments.

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0721777A3 (fr) * 1995-01-11 1997-03-05 Lilly Co Eli Utilisation de tomoxetine pour le traitement de l'hyperactivité induite par les troubles d'attention
EP0756869A3 (fr) * 1995-07-24 1999-06-16 Eli Lilly And Company Utilisation de la duloxétine ou de N-alkyl-3-phényl-(2-alkylthiophénoxy)-propylamines pour le traitement des troubles de l'attention et de l'hyperactivité
EP1014971A4 (fr) * 1997-01-29 2000-07-05 Lilly Co Eli Traitement des troubles dysphoriques premenstruels
EP0919235A1 (fr) * 1997-09-23 1999-06-02 Eli Lilly And Company Utilisation d'un inhibiteur d'assimilation de norépinéphrine pour le traitement de trouble de la conduite
EP0919236A1 (fr) * 1997-09-23 1999-06-02 Eli Lilly And Company Utilisation d'un inhibiteur d'assimilation de norépinéphrine pour le traitement de trouble oppositionel provocant
US6028070A (en) * 1997-09-23 2000-02-22 Eli Lilly And Company Treatment of oppositional defiant disorder
US6184222B1 (en) 1997-09-23 2001-02-06 Eli Lilly And Company Treatment of conduct disorder
WO1999052531A1 (fr) * 1998-04-09 1999-10-21 Pharmacia & Upjohn Company Nouveaux traitements pour troubles nerveux
US6586427B2 (en) 1998-04-09 2003-07-01 Pharmacia & Upjohn Company Treatments for nervous disorders
US6630507B1 (en) 1998-04-21 2003-10-07 The United States Of America As Represented By The Department Of Health And Human Services Cannabinoids as antioxidants and neuroprotectants
EP1113797A4 (fr) * 1998-09-15 2006-07-05 Lilly Co Eli Traitement de douleur persistante
US6596756B1 (en) 1998-09-15 2003-07-22 Eli Lilly And Company Treatment of fibromyalgia
WO2000037073A1 (fr) * 1998-12-22 2000-06-29 Novartis Pharma Gmbh Utilisation d'antagonistes de recepteurs de 5ht3 aux fins de traitement du syndrome de fatigue chronique
US6610690B2 (en) 1999-07-01 2003-08-26 Pharmacia & Upjohn Company Method of treating or preventing fibromyalgia and other somatoform disorders with a highly selective norepinephrine reuptake inhibitor
US7317011B2 (en) 1999-07-01 2008-01-08 Pharmacia & Upjohn Method of treating peripheral neuropathy
US7723334B2 (en) 1999-07-01 2010-05-25 Pfizer Inc. Highly selective norepinephrine reuptake inhibitors and methods of using the same
US6703389B2 (en) 1999-07-01 2004-03-09 Pharmacia & Upjohn Company Method of treating chronic pain
US7338953B2 (en) 1999-07-01 2008-03-04 Pharmacia & Upjohn Company Method of treating chronic fatigue syndrome
US7276503B2 (en) 1999-07-01 2007-10-02 Pharmacia & Upjohn Company Method of treating chronic fatigue syndrome
US6987107B2 (en) 1999-07-01 2006-01-17 Pharmacia & Upjohn Company Method of treating incontinence
US6465458B1 (en) 1999-07-01 2002-10-15 Pharmacia & Upjohn Company Method of treating or preventing chronic pain with a highly selective norepinephrine reuptake inhibitor
US7241762B2 (en) 1999-07-01 2007-07-10 Pharmacia & Upjohn Company Method of treating peripheral neuropathy
US7718705B1 (en) 1999-09-03 2010-05-18 Eli Lilly And Company Methods of using rapid-onset selective serotonin reuptake inhibitors for treating sexual dysfunction
WO2003011289A1 (fr) * 2001-07-31 2003-02-13 Pharmacia + Upjohn Company Traitement des douleurs chroniques au moyen de 3-heterocyclyl- et 3-cycloalkyl-3-aryloxypropanamines
WO2003053426A1 (fr) * 2001-12-19 2003-07-03 Cypress Bioscience, Inc. Procedes pour traiter le syndrome de fibromyalgie, le syndrome de fatigue chronique et la douleur
EP1499309A4 (fr) * 2002-04-24 2008-05-28 Cypress Bioscience Inc Prevention et traitement de troubles somatiques fonctionnels, y-compris les troubles lies au stress
WO2004019948A1 (fr) * 2002-08-29 2004-03-11 Arachnova Therapeutics Ltd. Nouvelles utilisations therapeutiques de la (4-(2-fluorophenyl)-6-methyl-2--(1-piperazinyl) thieno[2,3-d]pyrimidine
WO2004060366A1 (fr) * 2002-12-17 2004-07-22 Pharmacia Corporation Methode de traitement, de prevention ou d'inhibition d'un trouble du snc et/ou de la douleur et d'une inflammation, au moyen d'une combinaison de duloxetine, de venlafaxine ou d'atomoxetine et d'un inhibiteur selectif de la cyclo-oxygenase-2 et de ses compositions

Also Published As

Publication number Publication date
AU4131296A (en) 1996-05-15
ZA958725B (en) 1997-04-16
IL115664A0 (en) 1996-01-19

Similar Documents

Publication Publication Date Title
WO1996012485A1 (fr) Traitement de troubles au moyen de la duloxetine
US20240189261A1 (en) Methods and compositions for treating sleep apnea
JP6077053B2 (ja) 体重減少の達成および肥満症の治療のための漸増用量投与計画（ｅｓｃａｌａｔｉｎｇｄｏｓｉｎｇｒｅｇｉｍｅｎ）
US20060252761A1 (en) Augmentation of extinction via administration of sub-antimicrobial doses of D-cycloserine
US9918948B2 (en) Methods and compositions for treating symptoms associated with post-traumatic stress disorder using cyclobenzaprine
JPH0789851A (ja) 置換フェネチルアミン類を用いた医薬組成物
JP2004518653A (ja) 不安障害を治療する方法
WO2007046347A1 (fr) Produit pharmaceutique destine a proteger un nerf moteur chez les patients atteints de sclerose laterale amyotrophique
JP2012197304A (ja) ミオパシー関連性の覚醒障害を矯正することが意図される医薬品を製造するためのモダフィニルの使用
Westcott Modafinil, sleep deprivation, and cognitive function in military and medical settings
EP1429712B1 (fr) Methode de traitement de la constriction bronchiale et du bronchospasme
AU2002323191A1 (en) Method for treating bronchial constriction and bronchospasm
AU2019213277B2 (en) Compositions and methods for treating obstructive sleep apnea
JP2025512495A (ja) 発作性障害の治療
IL261984A (en) Sultiame for the treatment of sleep apnea
AU676672B2 (en) Brofaromine as an agent for treating post-traumatic stress
RU2143264C1 (ru) Способ лечения трахеитов
Chartier et al. Baclofen-Induced Neurotoxicity
DE2712432A1 (de) N-propargyl-piperonylamin, verfahren zu seiner herstellung und es enthaltende arzneimittel
EP2891491A1 (fr) Utilisation de (r) -phénylpiracétame pour le traitement de troubles du sommeil
KR20250000641A (ko) 수면장애 및/또는 수면장애 관련 질환을 예방, 개선 또는 치료하는 방법
Gursahani et al. Fatal cardiac dysrhythmia following a bupropion overdose in an adolescent
Derman et al. Sleep Disorders and their Psychiatric Significance
Fitzgerald Pharmacologic highlights: The beta-2 agonists
Lung et al. Medications in the allergy/asthma office

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IS JP KE KG KP KR KZ LK LR LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TT UA UG UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE MW SD SZ UG AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase