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WO2002019998A2 - Traitement des prises de poids associees a l'utilisation d'antipsychotiques atypiques - Google Patents

Traitement des prises de poids associees a l'utilisation d'antipsychotiques atypiques Download PDF

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Publication number
WO2002019998A2
WO2002019998A2 PCT/US2001/022621 US0122621W WO0219998A2 WO 2002019998 A2 WO2002019998 A2 WO 2002019998A2 US 0122621 W US0122621 W US 0122621W WO 0219998 A2 WO0219998 A2 WO 0219998A2
Authority
WO
WIPO (PCT)
Prior art keywords
cyclobutyl
chlorophenyl
dimethyl
administered
methylbutylamine hydrochloride
Prior art date
Application number
PCT/US2001/022621
Other languages
English (en)
Other versions
WO2002019998A3 (fr
Inventor
Alan Breier
Mark Louis Heiman
John David Leander
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 AU2001282913A priority Critical patent/AU2001282913A1/en
Publication of WO2002019998A2 publication Critical patent/WO2002019998A2/fr
Publication of WO2002019998A3 publication Critical patent/WO2002019998A3/fr

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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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • atypical antipsychotic agents is associated with weight gain in up to 50% of patients, a significant portion of the patient population.
  • Weight gain is now a well documented side effect of treatment with olanzapine.
  • Patients with schizophrenia are at risk for many health problems and weight gain increases the risk of obesity in these patients.
  • Obesity is a leading cause of mortality as it frequently leads to conditions such as diabetes and cardiovascular disorders. It ranks second only to smoking as a leading cause of preventable death. Left untreated, this scenario could eventually produce insulin resistance and perhaps diabetes in addition to obesity.
  • weight gain only complicates treatment of this disorder. While dietary' education and exercise can be used as part of the treatment program, this may not be sufficient intervention to prevent weight gain. In cases that are resistant to such lifestyle changes, drug intervention may be desired.
  • United States Patent No. 5,436,272 issued July 25, 1995 discloses a method of treating obesity in humans employing N,N-dimethyl-l- [1- (4-chlorophenyl) cyclobutyl] - 3 -methylbutylamine hydrochloride .
  • the present invention relates to a method for treating weight gain associated with atypical antipsychotic use which comprises administering to a mammal in need thereof a therapeutically effective amount of a triple reuptake inhibitor of norepinephrine, serotonin and dopamine .
  • the present invention provides a method of treating weight gain associated with atypical antipsychotic use which comprises administering to a mammal in need thereof a therapeutically effective amount of N, N-dimethyl-1- [1- (4-chlorophenyl) cyclobutyl] -3- methylbutylamine hydrochloride or a pharmaceutically acceptable salt or hydrate thereof.
  • the present invention further provides the use of N, N-dimethyl-1- [1- (4-chlorophenyl) cyclobutyl] -3- methylbutylamine hydrochloride or a pharmaceutically acceptable salt or hydrate thereof for the manufacture of a medicament for treatinq weiqht qain associated with atypical antipsychotic use.
  • the preferred atypical antipsychotic for use in the present invention is olanzapine.
  • the term “mammal” shall refer to the Mammalia class of higher vertebrates.
  • the term “mammal” includes, but is not limited to, a human.
  • the term “treating” as used herein includes prophylaxis of the named condition or amelioration or elimination of the condition once it has been established.
  • terapéuticaally effective means an amount sufficient to attenuate weight gain associated with atypical antipsychotic use.
  • Clozapine the prototypical atypical antipsychotic, differs from the typical antipsychotics with the following characteristics: (1) greater efficacy in the treatment of overall psychopathology in patients with schizophrenia ⁇ nonresponsive to typical antipsychotics; (2) greater efficacy in the treatment of negative symptoms of schizophrenia; and (3) less frequent and quantitatively smaller increases in serum prolactin concentrations associated with therapy (Beasley, et al . , Neuropsychopharmacology, 14(2), 111-123 , (1996)).
  • antipsychotic includes typical antipsychotics such as haliperidol and atypical antipsychotic such as olanzapine, risperidone, sertindole, Quetiapine, ziprasidone and clozapine.
  • Olanzapine, 2 -methyl-4- (4-methyl-1-piperazinyl) -10H- thieno [2 , 3-b] [1, 5] benzodiazepine, and its preferrred crystal form II is a known compound and is described in U.S. Patent Nos . 5,229,382 and 5,736,541 as being useful for the treatment of schizophrenia, schizophreniform disorder, acute mania, mild anxiety states, and psychosis . It is understood that the present invention includes all pharmaceutically acceptable salts, hydrates, solvates, and polymorphs of olanzapine.
  • Clozapine 8-chloro-ll- (4 -methyl-1-piperazinyl) -5H- dibenzo[b,e] [1, 4] diazepine, is described in U.S. Patent No . 3,539,573, which is herein incorporated by reference in its entirety. Clinical efficacy in the treatment of schizophrenia is described (Hanes, et al . , Psychophar acol . Bull . , 24, 62 (1988)).
  • Quetiapine 5- [2- (4-dibenzo [b, f] [1, 4] thiazepin-11- yl-1-piperazinyl) ethoxy] ethanol, and its activity in assays' which demonstrate utility in the treatment of schizophrenia are described in U.S. Patent No. 4,879,288, which is herein incorporated by reference in its entirety.
  • Quetiapine is typically administered as its (E) ⁇ 2-butenedioate (2:1) salt.
  • Triple reuptake inhibitors of norepinephrine , serotonin and dopamine preferably include compounds such as sibutramine (Meridia ® ) .
  • sibutramine Meridia ®
  • U. S. Patents 4,746,680 and 4,929,629 describes sibutramine and methods for making sibutramine and its monohydrate.
  • sibutramine N,N-dimethyl-l- [1- (4- chlorophenyl) -cyclobutyl] -3- methylbutylamine hydrochloride
  • British Patent Specification 2098602 and the use of N,N- dimethyl-1- [1- (4-chlorophenyl) cyclobutyl] -3- methylbutylamine hydrochloride in the treatment of Parkinson's disease is described in published PCT application WO 88/06444.
  • US Patent No. 5,436,272 discloses the use of sibutramine for the treatment of obesity.
  • a particularly preferred form of this compound is N,N-dimethyl-l- [1- (4-chlorophenyl) cyclobutyl] -3- methylbutylamine hydrochloride monohydrate (sibutramine hydrochloride) which is described in US Patent 4,929,629.
  • sibutramine includes racemates, enantiomers, solvateS', hydrates and pharmaceutically acceptable salts thereof.
  • the active compound may be administered orally, rectally, parenterally or topically, preferably orally.
  • the therapeutic compositions of the present invention may take the form of any of the known pharmaceutical compositions for oral, rectal, parenteral or topical administration.
  • Pharmaceutically acceptable carriers suitable for use in such compositions are well known in the art of pharmacy.
  • the compositions of the invention may contain 0.1-90% by weight of active compound.
  • the compositions of the invention are generally prepared in unit dosage form.
  • Compositions for oral administration are the preferred compositions of the invention and these are the known pharmaceutical forms for such administration, for example tablets, capsules, syrups and aqueous or oily suspensions.
  • the excipients used in the preparation of these compounds are the excipients known in the pharmacists' art.
  • Tablets may be prepared by mixing the active compound with an inert diluent such as calcium phosphate in the presence of disintegrating agents, for example maize starch, and lubricating agents, for example magnesium stearate, and tableting the mixture by known methods.
  • the tablets may be formulated in a manner known to those skilled in the art so as to give a sustained release of the compounds of the present invention.
  • Such tablets may, if desired, be provided with enteric coatings by known methods, for example by the use of cellulose acetate phthalate.
  • capsules for example hard or soft -gelatin capsules, containing the active compound with or without added excipients, may be prepared by conventional means and, if desired, provided with enteric coatings in a known manner.
  • compositions for oral administration include, for example, aqueous suspensions containing the active compound in an aqueous medium in the presence of a non-toxic suspending agent such as sodium carboxymethylcellulose, and oily suspensions containing a compound of the present invention in a suitable vegetable oil, for example arachis oil.
  • compositions for the invention suitable for rectal administration are the known pharmaceutical forms for such administration, for example suppositories with cocoa butter or polyethylene glycol bases.
  • compositions of the invention suitable for parenteral administration are the known pharmaceutical forms for such administration, for example sterile suspensions in aqueous and oily media or sterile solutions in a suitable solvent.
  • compositions for topical administration may comprise a matrix in which the pharmacologically active compounds of the present invention are dispersed so that the compounds are held in contact with the skin in order to administer the compounds transdermally.
  • the active compounds may be dispersed in a pharmaceutically acceptable cream or ointment base .
  • the compounds of the present invention in the form of particles of very small size, for example as obtained by fluid energy milling.
  • the active compound may, if desired, be associated with other compatible pharmacologically active ingredients.
  • the therapeutically active compound sibutramine may be administered in any of the known pharmaceutical dosage forms, for example solid dosage forms such as tablets or capsules, or liquid dosage forms, for example those forms intended for oral or parenteral administration.
  • the amount of the compound to be administered will depend on a number of factors including the age of the patient, the severity of the condition and the past medical history of the patient and always lies within the sound discretion of the administering physician but it is generally envisaged that the dosage of the compound to be administered will be in the range 0.1 to 50 mg preferably 1 to 30 mg per day given in one or more doses.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une méthode permettant de traiter les gains pondéraux associés à l'utilisation d'antipsychotiques atypiques. Cette méthode consiste à administrer à un mammifère nécessitant un tel traitement une dose thérapeutiquement efficace de chlorhydrate de N,N-diméthyl-1-[1-(4-chlorophényl) cyclobutyl]-3-méthylbutylamine.
PCT/US2001/022621 2000-09-08 2001-08-24 Traitement des prises de poids associees a l'utilisation d'antipsychotiques atypiques WO2002019998A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001282913A AU2001282913A1 (en) 2000-09-08 2001-08-24 A method of treating weight gain associated with atypical antipsychotic use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US23106500P 2000-09-08 2000-09-08
US60/231,065 2000-09-08

Publications (2)

Publication Number Publication Date
WO2002019998A2 true WO2002019998A2 (fr) 2002-03-14
WO2002019998A3 WO2002019998A3 (fr) 2003-01-23

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/022621 WO2002019998A2 (fr) 2000-09-08 2001-08-24 Traitement des prises de poids associees a l'utilisation d'antipsychotiques atypiques

Country Status (2)

Country Link
AU (1) AU2001282913A1 (fr)
WO (1) WO2002019998A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004000830A1 (fr) 2002-06-19 2003-12-31 Biovitrum Ab Nouveaux composes, leur utilisation et leur preparation
WO2009059418A1 (fr) * 2007-11-05 2009-05-14 Diane Mcintosh Procédés et compositions pour retarder une prise de poids associée à l'utilisation de médicaments antipsychotiques atypiques
US7550489B2 (en) 2002-03-12 2009-06-23 Merck & Co., Inc. Substituted pyridyoxy amides
US10154988B2 (en) 2012-11-14 2018-12-18 The Johns Hopkins University Methods and compositions for treating schizophrenia

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IE61928B1 (en) * 1988-11-29 1994-11-30 Boots Co Plc Treatment of obesity
EG23659A (en) * 1995-03-24 2007-03-26 Lilly Co Eli Process and crystal forms of methyl-thieno-benzodiazepine
BR0009159A (pt) * 1999-03-19 2001-12-26 Knoll Gmbh Método de controle do ganho de peso associadocom drogas terapêuticas

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7550489B2 (en) 2002-03-12 2009-06-23 Merck & Co., Inc. Substituted pyridyoxy amides
US7816534B2 (en) 2002-03-12 2010-10-19 Merck Sharp & Dohme Corp. Substituted amides
WO2004000830A1 (fr) 2002-06-19 2003-12-31 Biovitrum Ab Nouveaux composes, leur utilisation et leur preparation
WO2009059418A1 (fr) * 2007-11-05 2009-05-14 Diane Mcintosh Procédés et compositions pour retarder une prise de poids associée à l'utilisation de médicaments antipsychotiques atypiques
JP2011502175A (ja) * 2007-11-05 2011-01-20 マッキントッシュ、ダイアン 非定型抗精神病薬の使用に関連した体重増加を遅延させるための方法および組成物
CN104069498A (zh) * 2007-11-05 2014-10-01 黛安娜·麦金托什 用于延迟与使用非典型抗精神病药有关的体重增加的方法和组合物
EA020739B1 (ru) * 2007-11-05 2015-01-30 Дайана Макинтош Способы и композиции для замедления набора веса, связанного с применением атипичных антипсихотических препаратов
US10154988B2 (en) 2012-11-14 2018-12-18 The Johns Hopkins University Methods and compositions for treating schizophrenia
EP3610890A1 (fr) 2012-11-14 2020-02-19 The Johns Hopkins University Procédés et compositions de traitement de la schizophrénie
US10624875B2 (en) 2012-11-14 2020-04-21 The Johns Hopkins University Methods and compositions for treating schizophrenia

Also Published As

Publication number Publication date
WO2002019998A3 (fr) 2003-01-23
AU2001282913A1 (en) 2002-03-22

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