WO1992018005A1 - Procede de traitement de la trichotillomanie et de l'onychophagie - Google Patents
Procede de traitement de la trichotillomanie et de l'onychophagie Download PDFInfo
- Publication number
- WO1992018005A1 WO1992018005A1 PCT/US1992/003125 US9203125W WO9218005A1 WO 1992018005 A1 WO1992018005 A1 WO 1992018005A1 US 9203125 W US9203125 W US 9203125W WO 9218005 A1 WO9218005 A1 WO 9218005A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- clomipramine
- trichotillomania
- onychophagia
- serotonin reuptake
- fluoxetine
- Prior art date
Links
- 208000002271 trichotillomania Diseases 0.000 title claims abstract description 26
- 206010057342 Onychophagia Diseases 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 20
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 claims abstract description 23
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- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 claims abstract description 12
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims abstract description 11
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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
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
-
- 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
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Definitions
- the invention relates to the treatment of the psychiatric conditions such as trichotillomania and onychophagia
- the drugs of choice are serotonin reuptake inhibitors such as clomipraroine (ANAFRANIL R ), fluoxetine
- Trichotillomania is a common disorder characterized by plucking of hairs from head eyelashes, eyebrows and, less commonly, from other parts of the body. While this behavior may rarely accompany classical obsessive compulsive disorder (OCD) or schizophrenia or depression, the condition is not considered to be part of OCD, schizophrenia or depression and usually is the only disorder present. Similarly onychophagia (pathologic na i l biting) may occasionally co-exist with these same diseases .
- OCD is classified by DSM-III as an anxiety disorder .
- Trichoti llomania is classified by the DSM-III as an impulse control disorder such as kleptomania , pyromania , intermittent explosive disorder and pathological gambling .
- DSM-III distinguishes between the two separate disorders suggesting different etiology, natural history, and treatment response .
- Serotonin reuptake inhibitors are chemicals whose primary mechanism of action is blocking the reuptake of serotonin as opposed to blocking the uptake of noradrenaline or dopamine.
- Clomipramine in obsessive compulsive patients was believed by many authorities to be of value in treating OCD but only in patients having OCD accompanied by depression. For example, Marks and his associates stated, "when depression is minimal, clomipramine has no demonstratable value. ...Clomipramine effects mood more than rituals.”
- Fluoxetine hydrochloride ⁇ ( ⁇ )-N-methyl-3-phenyl-3-[( ⁇ , ⁇ , ⁇ -trifluoro-p-tolyl)-oxy]-propylamine hydrochloride ⁇ is a known antidepressant which is known to inhibit the reuptake of
- Fluvoxamine malate [5-methoxy-4'-(trifluromethyl) valerophenone-(E)-O-(2-aminoethyl)oxime maleate (1:1)] is a known antidepressant compound which is known to inhibit serotonin reuptake. Its chemical formula is:
- Zimelidine is another known inhibitor of serotonin reuptake and its chemical formula is:
- inhibitors such as clomipramine, fluoxetine, fluvoxamine , zimelidine and sertraline are effective in treating other psychiatric disorders such as impulse control disorders such as trichotillomania and also the disorder onychophagia .
- One aspect of the invention is the use of these types of compounds to treat a number of psychological and psychiatric conditions which were previously not known to be treated
- impulse disorders such as trichotillomania , pathological
- preferred conditions to treat with serotonin reuptake inhibitors are trichotillomania, onychophagia and other pathological
- Such conditions include repetitive or compulsive picking at the skin , (especially face picking) , preening, licking or examining skin or other parts of the body regardless of whether or not they are classified as impulse control disorders .
- serotonin reuptake inhibitors known well enough to give to a human are clomipramine, fluvoxamine and fluoxetine. It is contemplated that other serotonin reuptake inhibitors especially those previously tried in humans such as zimelidine and sertraline will also be effective for the same purposes in pharmacologically acceptable concentrations.
- psychiatric conditions within the same class of disorders as trichotillomania may also be treated with serotonin reuptake inhibitors as well.
- Serotonin reuptake inhibitors may be administered in any pharmaceutically acceptable carrier and may be of any pharmaceutically acceptable salt.
- the hydrochloride salt is particularly preferred for clomipramine and fluoxetine whereas the maleate is particularly preferred for fluvoxamine.
- Combinations of one or more additional medications with the serotonin reuptake inhibitor contemplated may be used as
- the preferred dosage for clomipramine is about 10 to about 300 rog/day.
- the preferred dosage for fluoxetine is about 5 to about 80 mg/day.
- the preferred dosage for fluvoxamine is about 10 to about 300 mg/day.
- the preferred dosage for zimelidine and sertraline is about 10 to about 300 mg/day.
- the dosage may be administered daily or may be divided for administration 2-6 times per day. Dosages given less often than daily may also be used.
- the pharmaceutically acceptable salts, esters, salts of such esters, nitrile oxides, or any other covalent linked or non-linked compounds which upon administration to the cells or individual, is capable of providing (directly or indirectly) the compounds of the invention or a biologically active metabolite thereof. All of these compounds are active and relatively non-toxic at concentrations sufficient for effective inhibition of the
- the compounds of the present invention may be administered alone in solution.
- the active ingredient(s) may be used or administered in a pharmaceutical formulation. These formulations comprise at least one active ingredient, together with one or more
- pharmaceutically acceptable carriers and possibly other active or inactive therapeutic ingredients.
- accepted is defined as being compatible with other ingredients of the formulation and relatively non- injurious to the patient or host cell.
- carriers include those well known to practitioners in the art as suitable for oral, rectal, nasal, topical, buccal, sublingual, vaginal,
- transdermal subcutaneous, intradermal, intramuscular,
- Formulations of the present invention suitable for ora l administration include sustained release formulations and may be presented in discrete units such as capsules , cachets , spansules or tablets each containing a predetermined amount of the active ingredient (s) .
- the shape and form of the solid are immaterial and it may be composed of smaller solids such as powders or granules .
- the formulation may be in liquid form such as a solution , suspension, oil-in-water or water-in-oil emulsion.
- compositions include a bolus , electuary or paste .
- Spansules of slow release in the gastrointestinal tract are particularly preferred.
- the oral dose may optionally be provided with an enteric coating to provide release in any part of the digestive track so desired.
- Formulations suitable for topical administration in the mouth include lozenges comprising the active ingredient with an acceptable flavorant such as sucrose and acacia or tragacanth; with an inert ingredient (s) such as gelatin or glycerin; or a combination of both .
- Mouthwash comprising the active ingredient and a liquid carrier are also acceptable in accordance with the invention.
- Formulations for topical and transdermal administration include a suitable carrier such as a cream or base of other material to facilitate contact with the skin or mucus membranes.
- a suitable carrier such as a cream or base of other material to facilitate contact with the skin or mucus membranes.
- the active ingredient(s) contained therein may be charged, or converted into a salt in order to permit crossing the surface under the influence of an electrical field.
- the active ingredient may be derivatized in order to enhance
- Formulations for rectal administration may be presented as a suppository with a suitable base, for example, comprising cocoa butter or a salicylate.
- Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulas containing such carriers as are known in the art to be appropriate in addition to the active ingredient(s).
- Formulations suitable for parenteral administration include aqueous and non-aqueous, isotonic and isosmotic sterile injection solutions which may contain antioxidants, buffers, bacteriostats, and solutes which render the formulation isotonic with the body fluids of the intended recipient and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.
- the formulations may be presented in unit-dose or multi-dose sealed containers, such as ampules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier (e.g. water, saline) for injection immediately prior to use.
- the sterile liquid carrier e.g. water, saline
- the final product is preferably free of pyrogens.
- Fluoxetine was also given to two trichotillomania patients after the double blinded study was complete and showed a
- the base-line impairment scores were 6 and 7 and after six months the scores were 2 and 3 respectively.
- Trichotillomanis impairment 6.8 ⁇ 1.7 6.6 ⁇ 1.0 6.2 ⁇ 1.7 4.2 ⁇ 2.7 2.47 0.03
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- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
Nouveaux procédés d'utilisation d'inhibiteurs de recaptage de sérotonine tels que la clomipramine, la fluvoxamine, la fluoxétine et la zimélidine. On peut citer parmi les maladies psychiatriques à traiter les troubles du contrôle des impulsions tels que la trichotillomanie, le jeu sous forme de pathologie, la pyromanie, la cleptomanie et les troubles caractériels intermittents. On peut également traiter d'autres états tels que l'onychophagie à l'aide des mêmes médicaments. Les données cliniques obtenues à partir de sujets humains dans le traitement de la trichotillomanie (tic consistant à s'arracher les cheveux) et l'onychophagie (tic consistant à se ronger les ongles) sont particulièrement prometteuses.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US68575291A | 1991-04-16 | 1991-04-16 | |
US685,752 | 1991-04-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992018005A1 true WO1992018005A1 (fr) | 1992-10-29 |
Family
ID=24753533
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1992/003125 WO1992018005A1 (fr) | 1991-04-16 | 1992-04-16 | Procede de traitement de la trichotillomanie et de l'onychophagie |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU1919592A (fr) |
WO (1) | WO1992018005A1 (fr) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6203817B1 (en) | 1997-02-19 | 2001-03-20 | Alza Corporation | Reduction of skin reactions caused by transdermal drug delivery |
US6512010B1 (en) | 1996-07-15 | 2003-01-28 | Alza Corporation | Formulations for the administration of fluoxetine |
US6517866B1 (en) | 1997-07-01 | 2003-02-11 | Pfizer Inc. | Sertraline salts and sustained-release dosage forms of sertraline |
WO2003073988A3 (fr) * | 2002-02-28 | 2004-08-05 | A & D Bioscience Inc | Glycuronamides, glycosides et glycosides d'orthoester de fluoxetine, analogues et utilisation de ceux-ci |
WO2005060968A1 (fr) | 2003-12-11 | 2005-07-07 | Sepracor Inc. | Combinaison d'un sedatif et d'un modulateur des neurotransmetteurs, et methodes permettant d'ameliorer la qualite du sommeil et de traiter la depression |
US6960613B2 (en) | 1999-07-08 | 2005-11-01 | H. Lundbeck A/S | Treatment of neurotic disorders |
WO2011069075A2 (fr) | 2009-12-04 | 2011-06-09 | Grant Jon E | Traitement de troubles du contrôle des impulsions au moyen d'inhibiteurs de la catéchol-o-méthyltransférase |
WO2015066344A1 (fr) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | Agonistes du récepteur 5-ht2c et compositions et procédés d'utilisation |
WO2016176177A1 (fr) | 2015-04-27 | 2016-11-03 | Arena Pharmaceuticals, Inc. | Agonistes des récepteurs 5-ht2c et compositions et méthodes d'utilisation |
WO2018035477A1 (fr) | 2016-08-19 | 2018-02-22 | Arena Pharmaceuticals, Inc. | Agonistes des récepteurs 5-ht2c, compositions et méthodes d'utilisation |
US10272094B2 (en) | 2015-07-31 | 2019-04-30 | Arena Pharmaceuticals, Inc. | 5-HT2C receptor agonists and compositions and methods of use |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5008262A (en) * | 1988-04-19 | 1991-04-16 | The United States Of America As Represented By The Department Of Health And Human Services | Method of treating trichotillomania and onchyphagia |
-
1992
- 1992-04-16 WO PCT/US1992/003125 patent/WO1992018005A1/fr active Application Filing
- 1992-04-16 AU AU19195/92A patent/AU1919592A/en not_active Abandoned
Patent Citations (1)
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---|---|---|---|---|
US5008262A (en) * | 1988-04-19 | 1991-04-16 | The United States Of America As Represented By The Department Of Health And Human Services | Method of treating trichotillomania and onchyphagia |
Non-Patent Citations (4)
Title |
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J. CLINICAL PSYCHIATRY, Vol 52, No. 2, issued February 1991, M.A. STANLEY et al., "Treatment of Trichofillomania with Fluoxetine", see page 252. * |
J. CLINICAL PSYCHIATRY, Vol. 52, No. 6, issued June 1991, ALEXANDER, "Fluoxetine Treatment of Trichofillomania", see page 88. * |
PSYCHIATRY, Vol. 26, No. 2, issued 1985, K.R.R. KRISHNAN et al., "Trichotillomania a Review", pages 123-128. * |
THE JOURNAL OF NERVOUS AND MENTAL DISEASE, Volume 168, No. 8, issued 1980, S. SNYDER, "Trichotillomania Treated with Amitriptyline", pages 505-507. * |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6512010B1 (en) | 1996-07-15 | 2003-01-28 | Alza Corporation | Formulations for the administration of fluoxetine |
US7011844B2 (en) | 1996-07-15 | 2006-03-14 | Alza Corporation | Formulations for the administration of fluoxetine |
US6203817B1 (en) | 1997-02-19 | 2001-03-20 | Alza Corporation | Reduction of skin reactions caused by transdermal drug delivery |
US6517866B1 (en) | 1997-07-01 | 2003-02-11 | Pfizer Inc. | Sertraline salts and sustained-release dosage forms of sertraline |
US6960613B2 (en) | 1999-07-08 | 2005-11-01 | H. Lundbeck A/S | Treatment of neurotic disorders |
US7265151B2 (en) | 1999-07-08 | 2007-09-04 | H. Lundbeck A/S | Treatment of neurotic disorders |
US7271194B2 (en) | 1999-07-08 | 2007-09-18 | H. Lundbeck A/S | Treatment of neurotic disorders |
WO2003073988A3 (fr) * | 2002-02-28 | 2004-08-05 | A & D Bioscience Inc | Glycuronamides, glycosides et glycosides d'orthoester de fluoxetine, analogues et utilisation de ceux-ci |
US7217696B2 (en) | 2002-02-28 | 2007-05-15 | A & D Bioscience, Inc. | Glycuronamides, glycosides and orthoester glycosides of fluoxetine, analogs and uses thereof |
EP2343073A2 (fr) | 2003-12-11 | 2011-07-13 | Sepracor Inc. | Combinaison de sédatif et modulateur neurotransmetteur et procédés d'amélioration de la qualité du sommeil et de traitement de la dépression |
WO2005060968A1 (fr) | 2003-12-11 | 2005-07-07 | Sepracor Inc. | Combinaison d'un sedatif et d'un modulateur des neurotransmetteurs, et methodes permettant d'ameliorer la qualite du sommeil et de traiter la depression |
WO2011069075A2 (fr) | 2009-12-04 | 2011-06-09 | Grant Jon E | Traitement de troubles du contrôle des impulsions au moyen d'inhibiteurs de la catéchol-o-méthyltransférase |
US8598235B2 (en) | 2009-12-04 | 2013-12-03 | Jon E. Grant | Treating impulse control disorders with catechol-O-methyl-transferase inhibitors |
WO2015066344A1 (fr) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | Agonistes du récepteur 5-ht2c et compositions et procédés d'utilisation |
WO2016176177A1 (fr) | 2015-04-27 | 2016-11-03 | Arena Pharmaceuticals, Inc. | Agonistes des récepteurs 5-ht2c et compositions et méthodes d'utilisation |
US10272094B2 (en) | 2015-07-31 | 2019-04-30 | Arena Pharmaceuticals, Inc. | 5-HT2C receptor agonists and compositions and methods of use |
US10624900B2 (en) | 2015-07-31 | 2020-04-21 | Arena Pharmaceuticals, Inc. | 5-HT2C receptor agonists and compositions and methods of use |
US11395824B2 (en) | 2015-07-31 | 2022-07-26 | Arena Pharmaceuticals, Inc. | 5-HT2C receptor agonists and compositions and methods of use |
WO2018035477A1 (fr) | 2016-08-19 | 2018-02-22 | Arena Pharmaceuticals, Inc. | Agonistes des récepteurs 5-ht2c, compositions et méthodes d'utilisation |
US10836764B2 (en) | 2016-08-19 | 2020-11-17 | Arena Pharmaceuticals, Inc. | 5-HT2C receptor agonists and compositions and methods of use |
US11608339B2 (en) | 2016-08-19 | 2023-03-21 | Arena Pharmaceuticals, Inc. | 5-HT2C receptor agonists and compositions and methods of use |
Also Published As
Publication number | Publication date |
---|---|
AU1919592A (en) | 1992-11-17 |
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