GB2340037A - Compositions comprising bupropion for the treatment of premature ejaculation - Google Patents
Compositions comprising bupropion for the treatment of premature ejaculation Download PDFInfo
- Publication number
- GB2340037A GB2340037A GB9917346A GB9917346A GB2340037A GB 2340037 A GB2340037 A GB 2340037A GB 9917346 A GB9917346 A GB 9917346A GB 9917346 A GB9917346 A GB 9917346A GB 2340037 A GB2340037 A GB 2340037A
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- GB
- United Kingdom
- Prior art keywords
- bupropion
- premature ejaculation
- treating
- induced
- susceptible
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- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Reproductive Health (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
2340037 Medicament for Treating Premature Ejaculation
This application claims priority to US Provisional Application 60/094,701 filed July 30, 1998, the entire disclosure of which is considered part of this application and is herein incorporated by reference.
This invention relates to a new medical use for and compositions containing bupropion and physiologically acceptable salts and solvates thereof. The invention concerns use of bupropion in treating premature ejaculation that is primarily caused by a physical disorder. Specifically the invention concerns the use of bupropion in treating premature ejaculation, which is sometimes induced following administration of sildenafil or other cGIVIP PIDE and PDE V inhibitors.
The invention also concerns pharmaceutical compositions comprising bupropion and sildenafil.
Bupropion hydrochloride, ( )-l-(3-chlorophenyl)-2-[(1,1dimethylethyl)amino]-lpropanone hydrochloride, is the active ingredient of Wellbutrin and Wellbutrin'SR which are marketed in the United States for the treatment of depression. It is also the active ingredient of Zyban' which is marketed in the United States as an aid to smoking cessation. The term "bupropion" herein includes all physiologically acceptable salts and solvates thereof and all enantiomers thereof.
Sildenafil citrate, 1-[[3-(6,7-dihydro-l-methyl-7-oxo-3-propyl-lHpyrazolo [4,3- d]pyrimidin-5-yl)-4-ethoxyphenyl] suffonyl]-4-methylpiperazine citrate, is the active ingredient in VIAGRA', which is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) and is marketed in the United states as an oral therapy for erectile dysfunction. The term "sildenafil" herein includes all physiologically acceptable salts and solvates thereof.
Bupropion is a relatively weak inhibitor of the neuronal uptake of noradrenaline (NA), serotonin and dopamine (DA), and does not inhibit monoamine oxidase. While the mechanism of action of bupropion, as with other antidepressants, is unknown, it is presumed that this action is mediated by noradrenergic and/or 2 doparninergic mechanisms. Available evidence suggests that bupropion is a selective inhibitor of noradrenaline (NA) at doses that are predictive of antidepressant activity in animal models. See Ascher, J.A., et aL, Bupropion: A Review of its Mechanism of Antidepressant Activity. Journal of Clinical Psychiatry, 56: p. 395-401,1995.
C1 0 CH3 H3C N CH3 - HC1 H3C H Bupropion HC1 It has also been disclosed that buproplon is useful for the treatment of migraine (U.S. 5,753,712), reducing cholesterol (U.S. 4,438,138), treatment of minimal brain dysfunction (U.S. 4,435,449), treatment of tardive dyskinesia (U.S.
4,425,363), reversing impaired mental alertness due to ethanol consumption (U.S. 4,393,078) and suppressing prolactin secretion (U.S. 4, 347,257).
It has further been disclosed in U.S. 4,507,323 that bupropion is useful for the treatment of psychosexual dysfunction, e.g., premature ejaculation, wherein said dysfunctions are those in which a physical disorder or another AXIS I mental disorder, e.g., major depression, is not the primary cause of disturbance in sexual function.
3 Sildenafil is disclosed, for example in European Patent No 463756 and may be represented by the formula 0 Me I Me N 0 N N I N S N Pr-n OB The compounds described in the aforementioned patent specification are described as potent inhibitors of cyclic guanosine 31,5'-monophosphate phosphodiesterases (cGMP PDEs). EP-A-0463756 and EP-A-0526004 describe such cGMP PDE inhibitors as having utility in the treatment of stable, unstable, 10 and variant (Prinzmetal) angina, hypertension, pulmonary hypertension, congestive heart failure, atherosclerosis, conditions of reduced blood vessel patency, e.g. post-percutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, stroke, bronchitis, allergic asthma, chronic asthma, allergic rhinitis, glaucoma and diseases characterised by disorders of gut motility, 15 e.g. irritable bowel syndrome (113S). W094/28902 discloses the use of cGMP PDE inhibitors in treating male erectile dysfunction. Sildenafil is normally administered as an oral dosage form, typically a tablet, containing 25mg, 50mg or 1 00mg of the active ingredient. Later publications, for example Eardley, 1. Exp. Opin. Invest. Drugs (1997) 6 (12) 20 1803-1810 have confirmed that sildenafil is a specific inhibitor of the particular physiological isoform (Type V) of the cGMP PDE enzyme found in the penis. Thus, sildenafil can also be described as a PDE V inhibitor.
4 It has been found that premature ejaculation is sometimes induced following administration of the drug sildenafil. Other cGMP PDE, particularly PDE V inhibitors may also induce premature ejaculation.
Surprisingly, it has been found that bupropion is useful for the treatment of premature ejaculation that is primarily caused by a physical disorder.
Specifically, it has been found that bupropion is useful for the treatment of cGMP PIDE and PIDE V inhibitor-induced premature ejaculation and not merely premature ejaculation related to psychosexual dysfunction (U.S. 4,507, 323).
More specifically, it has been found that bupropion is useful for the treatment of sildenafil-induced premature ejaculation.
According to one aspect of the present invention, there is provided a method of treating a human suffering from or susceptible to premature ejaculation that is primarily caused by a physical disorder comprising administering an effective amount of bupropion.
According to a second aspect of the present invention, there is provided a method of treating a human suffering from or susceptible to premature ejaculation induced by cGMP PDE inhibitors which comprises administering an effective amount of bupropion.
According to a third aspect of the invention, there is provided a method of treating a human suffering from or susceptible to premature ejaculation induced by cGMP PDE V inhibitors which comprises administering an effective amount of bupropion.
According to a fourth aspect of the invention, there is provided a method of treating a human suffering from or susceptible to premature ejaculation induced by sildenafil which comprises administering an effective amount of bupropion.
The invention also provides, in a fifth aspect, pharmaceutical compositions for the treatment of premature ejaculation primarily caused by a physical disorder or premature ejaculation induced by cGMP PIDE inhibitors, cGMP PDE V inhibitors or sildenafil comprising bupropion as the active ingredient.
According to a sixth aspect of the present invention there is provided the use of bupropion in the manufacture of a medicament for the treatment of a human suffering from or susceptible to premature ejaculation primarily caused by a physical disorder or premature ejaculation induced by cGMP PIDE, cGMP PIDE V inhibitors or sildenafil.
The invention further provides, in a seventh aspect, pharmaceutical compositions comprising buproplon and sildenafil (useful for the treatment of erectile dysfunction and sildenafil-induced premature ejaculation).
Compounds for use in the invention are suitably in the form of physiologically acceptable salts. These salts may include acid addition salts formed with organic or inorganic acids for example hydrochlorides, hydrobromides, sulphates, nitrates, phosphates, formates, mesylates, citrates, benzoates furnarates, maleates and succinates. Wellbutrin, Wellbutrin'OSR and Zyban9 employ the hyrdrochloride salt of bupropion. VIAGRAO employs the citrate salt of sildenafil.
Bupropion and/or sildenafil for use according to the invention may be administered as the raw chemical comprising the active compound. However, one or more of the following pharmaceutically acceptable formulations may also be employed. Conveniently, a compound for use according to the invention may be formulated in conventional manner using one or more pharmaceutically acceptable exciplents. Thus, a compound for use according to the invention may for example be formulated for oral, sub- lingual, buccal, parenteral, rectal or intranasal administration or in a form suitable for administration by inhalation or insufflation (either through the mouth or nose).
For oral administration the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g.
6 pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcel lu lose); fillers (e.g. lactose, microcrystalline cellulose or calcium phosphate); lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g. potato starch or sodium starch glycollate); or wetting agents (e.g. sodium lauryl sulphate). The tablets may be coated by methods well known in the art.
Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (following HBr removal sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agents (e.g. lecithin or acacia); non-aqueous vehicles (e.g. almond oil, oily esters or ethyl alcohol); and preservatives (e.g. methyl or propyl P-hydroxybenzoates or sorbic acid).
For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.
A compound for use according to the invention may be formulated for parenteral administration by injection, conveniently intravenous, in intramuscular or subcutaneous injection. Formulations for injection may be presented in unit dosage form e.g. in ampoules or in multi-dose containers, optionally with an added preservative.
The compositions for parenteral administration may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such ais suspending, stabilising and/or dispersing agents.
Alternatively, the active ingredient may be in dry form such as a powder, crystalline or freeze-dried solid for constitution with a suitable vehicle, e.g. sterile pyrogen-free water or isotonic saline before use. They may be presented, for example, in sterile ampoules or vials.
7 A compound for use according to the invention may also be formulated in rectal compositions such as suppositories or retention enemas, e.g. containing conventional suppository bases such as cocoa butter or other glyceride.
Tablets for sub-lingual administration may be formulated in a conventional 5 manner.
For intranasal administration a compound for use according to the invention may be used, for example, as a liquid in the form of a spray or drops or as a powder. Suitably the preparation for intranasal administration is delivered in the form of a spray or aerosol from an insufflator or from a pressurised pack or nebuliser with the use of a suitable propellant.
For administration by inhalation the compound for use according to the invention is conveniently delivered in the form of an aerosol spray presentation from pressurised packs or a nebuliser, with the use of a suitable propellant, e.g. dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurised aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of gelatin for use in an inhaler or insufflater may be formulated containing a powder mix of a compound of use in the invention and a suitable powder base such as lactose or starch.
Various formulations of bupropion have been disclosed in U.S. 5,427,798, U.S. 5,358,970, U.S. 5,541,231 and U.S. 5,731,000 (and other patents related to U.S. 5,358,970). It will be appreciated that the precise dose administered will depend on the particular compound used, the age and condition of the patient and the 25 frequency and route of administration and will be at the ultimate discretion of the attendant physician. The compound may be administered in single or divided doses and may be administered one or more times, for example 1 to 4 times per day.
8 Typically, bupropion is useful for the treatment of cGMP PIDE inhibitor-, cGMP PIDE V inhibitor- or sildenafil-induced premature ejaculation in an amount between 0.1 mg to 500 mg per day, more preferably in an amount between 25 mg and 300 mg per day and most preferably in an amount between 150 mg to 300 mg per day.
Typically, pharmaceutical compositions comprising bupropion and sildenafil (useful for the treatment of erectile dysfunction and sildenafil-induced premature ejaculation) comprise bupropion in the amount of 0.1 mg to 300 mg per unit dose, more preferably in an amount between 25 mg and 300 mg per unit dose and most preferably in an amount between 50 mg to 150 mg per unit dose and further comprise sildenafil in the in an amount between 1 mg to 200 mg per unit dose, preferably in an amount between 25 mg to 200 mg per unit dose and more preferably in an amount between 25 mg to 100 mg per unit dose.
I 9
Claims (8)
1. A method of treating a human suffering from or susceptible to premature ejaculation that is primarily caused by a physical disorder comprising administering an effective amount of bupropion.
2. A method of treating a human suffering from or susceptible to premature ejaculation induced by cGMP PDE inhibitors which comprises administering an effective amount of bupropion.
3. A method of treating a human suffering from or susceptible to premature ejaculation induced by cGMP PIDE V inhibitors which comprises administering an effective amount of bupropion.
4. A method of treating a human suffering from or susceptible to premature ejaculation induced by sildenafil which comprises administering an effective amount of bupropion.
5. A pharmaceutical composition for treating a human suffering from or susceptible to premature ejaculation that is primarily caused by a physical disorder which comprises bupropion as the active ingredient.
6. A pharmaceutical composition for treating a human suffering from or susceptible to premature ejaculation induced by cGMP PIDE inhibitors which comprises bupropion as the active ingredient.
7. A pharmaceutical composition for treating a human suffering from or susceptible to premature ejaculation induced by cGMP PIDE V inhibitors which comprises bupropion as the active ingredient.
8. A pharmaceutical composition for treating a human suffering from or susceptible to premature ejaculation induced by sildenafil which comprises bupropion as the active ingredient.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9470198P | 1998-07-30 | 1998-07-30 |
Publications (2)
Publication Number | Publication Date |
---|---|
GB9917346D0 GB9917346D0 (en) | 1999-09-22 |
GB2340037A true GB2340037A (en) | 2000-02-16 |
Family
ID=22246671
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB9917346A Withdrawn GB2340037A (en) | 1998-07-30 | 1999-07-26 | Compositions comprising bupropion for the treatment of premature ejaculation |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB2340037A (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002060424A2 (en) * | 2001-01-29 | 2002-08-08 | Sepracor, Inc. | Methods of using and compositions comprising sibutramine metabolites optionally in combination with other pharmacologically active compounds |
WO2002060428A2 (en) * | 2001-01-29 | 2002-08-08 | Sepracor, Inc. | Methods of using and compositions comprising (-)sibutramine optionally in combination with other pharmacologically active compounds |
WO2002060427A2 (en) * | 2001-01-29 | 2002-08-08 | Sepracor Inc. | Methods of using and compositions comprising (+) sibutramine optionally in combination with other pharmacologically active compounds |
WO2003000343A2 (en) * | 2001-06-21 | 2003-01-03 | Vivus, Inc. | Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation |
US6710087B2 (en) | 1999-08-11 | 2004-03-23 | Sepracor, Inc. | Methods of treating or preventing neuropathic pain using sibutramine metabolites |
US6974839B2 (en) | 2001-03-16 | 2005-12-13 | Dmi Biosciences, Inc. | Method of delaying ejaculation |
US6974838B2 (en) | 1998-08-24 | 2005-12-13 | Sepracor Inc. | Methods of treating or preventing pain using sibutramine metabolites |
EP1648430A1 (en) * | 2003-07-11 | 2006-04-26 | Worldwide PE Patent Holdco Pty Ltd | Treatment of premature ejaculation |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0171227A1 (en) * | 1984-07-25 | 1986-02-12 | The Wellcome Foundation Limited | Use of propiophenone compound |
-
1999
- 1999-07-26 GB GB9917346A patent/GB2340037A/en not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0171227A1 (en) * | 1984-07-25 | 1986-02-12 | The Wellcome Foundation Limited | Use of propiophenone compound |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6974838B2 (en) | 1998-08-24 | 2005-12-13 | Sepracor Inc. | Methods of treating or preventing pain using sibutramine metabolites |
US6710087B2 (en) | 1999-08-11 | 2004-03-23 | Sepracor, Inc. | Methods of treating or preventing neuropathic pain using sibutramine metabolites |
WO2002060427A3 (en) * | 2001-01-29 | 2003-02-13 | Sepracor Inc | Methods of using and compositions comprising (+) sibutramine optionally in combination with other pharmacologically active compounds |
WO2002060428A3 (en) * | 2001-01-29 | 2002-12-19 | Sepracor Inc | Methods of using and compositions comprising (-)sibutramine optionally in combination with other pharmacologically active compounds |
WO2002060424A3 (en) * | 2001-01-29 | 2003-02-06 | Sepracor Inc | Methods of using and compositions comprising sibutramine metabolites optionally in combination with other pharmacologically active compounds |
WO2002060424A2 (en) * | 2001-01-29 | 2002-08-08 | Sepracor, Inc. | Methods of using and compositions comprising sibutramine metabolites optionally in combination with other pharmacologically active compounds |
WO2002060427A2 (en) * | 2001-01-29 | 2002-08-08 | Sepracor Inc. | Methods of using and compositions comprising (+) sibutramine optionally in combination with other pharmacologically active compounds |
WO2002060428A2 (en) * | 2001-01-29 | 2002-08-08 | Sepracor, Inc. | Methods of using and compositions comprising (-)sibutramine optionally in combination with other pharmacologically active compounds |
US6974839B2 (en) | 2001-03-16 | 2005-12-13 | Dmi Biosciences, Inc. | Method of delaying ejaculation |
WO2003000343A2 (en) * | 2001-06-21 | 2003-01-03 | Vivus, Inc. | Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation |
WO2003000343A3 (en) * | 2001-06-21 | 2004-03-25 | Vivus Inc | Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation |
EP1648430A1 (en) * | 2003-07-11 | 2006-04-26 | Worldwide PE Patent Holdco Pty Ltd | Treatment of premature ejaculation |
EP1648430A4 (en) * | 2003-07-11 | 2009-01-14 | Worldwide Pe Patent Holdco Pty | Treatment of premature ejaculation |
Also Published As
Publication number | Publication date |
---|---|
GB9917346D0 (en) | 1999-09-22 |
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Legal Events
Date | Code | Title | Description |
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WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |