WO1989010123A1 - Flevoxate and derivatives for erectile dysfunctions - Google Patents
Flevoxate and derivatives for erectile dysfunctions Download PDFInfo
- Publication number
- WO1989010123A1 WO1989010123A1 PCT/EP1989/000417 EP8900417W WO8910123A1 WO 1989010123 A1 WO1989010123 A1 WO 1989010123A1 EP 8900417 W EP8900417 W EP 8900417W WO 8910123 A1 WO8910123 A1 WO 8910123A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- methylflavon
- treatment
- erectile
- erectile dysfunctions
- pharmaceutically acceptable
- Prior art date
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
- A61K31/395—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
Definitions
- This invention relates to the use of 3-methyl-f la- von-8-carboxyl ⁇ c acid and derivatives thereof for the preparation of a drug for the treatment and for the diagnosis of erectile impotence.
- the invention relates to pharma ⁇ ceutical compositions for the treatment of erectile impotence containing as the active principle 3-methylfla- von-8-carboxyl ⁇ c acid or a derivative thereof of formula I
- A is a linear or branched C -C alkyl residue
- Z is a dimethylamino, diethylammo, di-n-propylamino, di- lsopropylammo, piperidmo or morpholmo residue, or pharmaceutically acceptable salts thereof.
- Flavoxate is a very well tolerated drug; the large therapeutic index found in preclinical studies (C. Pietra et al., II Farmaco Ed. Prat., 4_1, 267, (1986)) and the absence of serious side effects during clinical application, attest its excellent tolerability. Particularly, cardiocirculatory complica ⁇ tions have never been reported. 3-methylflavon-8-carbo- xylic acid(MFCA) is the main metabolite of flavoxate. In terms of pharmacokinetics and - dynamics MFCA is most similar to flavoxate.
- Erectile dysfunction is a well known and common disease, of vascular, hormonal, neurogenic or psychogenic origin which causes impaired penile erection.
- the insufficient erectile ability of the penis has serious implications for psychological, physical and social well-being of the afflicted individuals. Self confidence in particular, and quality of life in general, are strongly reduced.
- Prosthetic devices that are implanted in the penis to mimic erection or are located outside in the scrotal sac or in an adjacent area to stimulate for instance to trasmitting electrical energy to the nervi erigentes.
- Pharmacological substances which are also injected directly into the corpora cavernosa, where they increase the inflow of blood and consequently generate tumescence of the penis, are also used.
- Human tissue was obtained from patients undergoing penile prothesis implantation.
- Biopsies of human corpus cavernosum tissue were obtained in the operating room and immediately placed in chilled (4°C) physiological salt solution of the following millimolar composition: NaCl 118.3; KC1 4.7; Mg ⁇ O 0.6; KH PO 1.2; CaCl 2.5; NaHCO 25.0; Calcium EDTA 0.026 and glucosio 11.1.
- the solution is gassed with 95% 0 , 5% CO ; pH maintained at 7.4 and temperature at 37°C.
- Isometric tension was measured throught the experiment with a tension transducer (Grass FT03, Quincy, MA) .
- the strips of corpus cavernosum were fixed with silk ties on one end to the electrode support and the other end to a wire connected to the force transducer.
- the strips were allowed to equilibrate for a period of approximately three hours.
- the optimal isometric tension for contraction was determined during this period by stepwise stretching of the tissue followed by
- Drugs were provided in powder form. Stock solutions were made in distilled water. For papaverine and flavoxate
- Flavoxate up to 10 M, induced relaxation of HCC contracted with norepinephrine, PG F2 alpha or potassium. Maximal relaxations to this concentration were: 73.1 +/- 7.7%, 66 +/- 13.2%, and 55.5 +/- 23% of maximal relaxation, respectively (see figures 1-3).
- the threshold for the response to flavoxate was approximately 3 x 10 M. The relaxation response was slow in onset and several minutes were required before the maximal relaxation
- 3-methylflavon-8-carboxylic acid and its basic esters of formula I, particularly flavoxate may be conveniently used in human therapy for the treatment of erectile impairments.
- pharmaceutical compositions suited for the oral, topical or parenteral (intracavernous) administration are provided.
- the oral administration is particularly convenient for its compliance and it is moreover useful as support therapy in patients who otherwise undergo papaverine or alpha-blockers injection. This regimen allows a reduction of the papaverine and alpha-blocker dosage and improves therefore the safe use of these agents.
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1019890702417A KR900700098A (ko) | 1988-04-22 | 1989-04-19 | 발기부전의 치료겸 진단용 플라복세이트 및 그 유도체 |
DK644589A DK644589A (da) | 1988-04-22 | 1989-12-19 | Flavoxat og derivater heraf til erektile forstyrrelser |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT20299A/88 | 1988-04-22 | ||
IT20299/88A IT1217190B (it) | 1988-04-22 | 1988-04-22 | Composti utili per il trattamento e diagnosi di disfunzioni frettili |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1989010123A1 true WO1989010123A1 (en) | 1989-11-02 |
Family
ID=11165532
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1989/000417 WO1989010123A1 (en) | 1988-04-22 | 1989-04-19 | Flevoxate and derivatives for erectile dysfunctions |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0374210A1 (ja) |
JP (1) | JPH02504146A (ja) |
KR (1) | KR900700098A (ja) |
AU (1) | AU3438289A (ja) |
HU (1) | HU202754B (ja) |
IT (1) | IT1217190B (ja) |
WO (1) | WO1989010123A1 (ja) |
ZA (1) | ZA892911B (ja) |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995028932A1 (en) * | 1994-04-22 | 1995-11-02 | Flora Inc. | Transdermal delivery of alpha adrenoceptor blocking agents |
US5981527A (en) * | 1995-07-14 | 1999-11-09 | Icos Corporation | Cyclic GMP-specific phosphodiesterase inhibitors |
US6001847A (en) * | 1995-07-14 | 1999-12-14 | Icos Corporation | Chemical compounds |
US6117881A (en) * | 1996-05-10 | 2000-09-12 | Icos Corporation | N-cinnamoyl derivatives of (β) carbolines |
US6140329A (en) * | 1995-07-14 | 2000-10-31 | Icos Corporation | Use of cGMP-phosphodiesterase inhibitors in methods and compositions to treat impotence |
US6143746A (en) * | 1994-01-21 | 2000-11-07 | Icos Corporation | Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use |
US6300335B1 (en) | 1994-11-26 | 2001-10-09 | Pfizer Inc. | 4-aminoquinazoline derivative cGMP-PDE inhibitors for the treatment of erectile dysfunction |
US6469012B1 (en) | 1993-06-09 | 2002-10-22 | Pfizer Inc | Pyrazolopyrimidinones for the treatment of impotence |
US6534511B1 (en) | 1994-11-26 | 2003-03-18 | Pfizer Inc. | Bicyclic heterocyclic compounds for the treatment of impotence |
US6821978B2 (en) | 2000-09-19 | 2004-11-23 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
US6943171B2 (en) | 2001-11-09 | 2005-09-13 | Schering Corporation | Polycyclic guanine derivative phosphodiesterase V inhibitors |
WO2011023287A1 (en) * | 2009-08-27 | 2011-03-03 | Merck Patent Gmbh | Use of faa and its derivatives in cosmetics and dermatology |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0266968A2 (en) * | 1986-11-03 | 1988-05-11 | Gérard G. Cohen | Gelled ointment of vasodilating agent |
-
1988
- 1988-04-22 IT IT20299/88A patent/IT1217190B/it active
-
1989
- 1989-04-19 KR KR1019890702417A patent/KR900700098A/ko not_active Application Discontinuation
- 1989-04-19 HU HU892651A patent/HU202754B/hu not_active IP Right Cessation
- 1989-04-19 AU AU34382/89A patent/AU3438289A/en not_active Abandoned
- 1989-04-19 EP EP89904810A patent/EP0374210A1/en not_active Withdrawn
- 1989-04-19 JP JP1504483A patent/JPH02504146A/ja active Pending
- 1989-04-19 WO PCT/EP1989/000417 patent/WO1989010123A1/en not_active Application Discontinuation
- 1989-04-20 ZA ZA892911A patent/ZA892911B/xx unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0266968A2 (en) * | 1986-11-03 | 1988-05-11 | Gérard G. Cohen | Gelled ointment of vasodilating agent |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6469012B1 (en) | 1993-06-09 | 2002-10-22 | Pfizer Inc | Pyrazolopyrimidinones for the treatment of impotence |
US6143746A (en) * | 1994-01-21 | 2000-11-07 | Icos Corporation | Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use |
US5503843A (en) * | 1994-04-22 | 1996-04-02 | Flora Inc. | Transdermal delivery of alpha adrenoceptor blocking agents |
US5658587A (en) * | 1994-04-22 | 1997-08-19 | Flora Inc. | Transdermal delivery of alpha adrenoceptor blocking agents |
WO1995028932A1 (en) * | 1994-04-22 | 1995-11-02 | Flora Inc. | Transdermal delivery of alpha adrenoceptor blocking agents |
US6656945B2 (en) | 1994-11-26 | 2003-12-02 | Pfizer Inc | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-one cGMP-PDE inhibitors for the treatment of erectile dysfunction |
US6300335B1 (en) | 1994-11-26 | 2001-10-09 | Pfizer Inc. | 4-aminoquinazoline derivative cGMP-PDE inhibitors for the treatment of erectile dysfunction |
US6534511B1 (en) | 1994-11-26 | 2003-03-18 | Pfizer Inc. | Bicyclic heterocyclic compounds for the treatment of impotence |
US6001847A (en) * | 1995-07-14 | 1999-12-14 | Icos Corporation | Chemical compounds |
US6218400B1 (en) | 1995-07-14 | 2001-04-17 | Icos Corporation | Treatment method using a cGMP-Specific PDE inhibitor |
US6140329A (en) * | 1995-07-14 | 2000-10-31 | Icos Corporation | Use of cGMP-phosphodiesterase inhibitors in methods and compositions to treat impotence |
US6143757A (en) * | 1995-07-14 | 2000-11-07 | Icos Corporation | Chemical compounds |
US6608065B1 (en) | 1995-07-14 | 2003-08-19 | Icos Corporation | Use of cGMP phosphodiesterase inhibitors in methods to treat female sexual dysfunction |
US5981527A (en) * | 1995-07-14 | 1999-11-09 | Icos Corporation | Cyclic GMP-specific phosphodiesterase inhibitors |
US6117881A (en) * | 1996-05-10 | 2000-09-12 | Icos Corporation | N-cinnamoyl derivatives of (β) carbolines |
US6306870B1 (en) | 1996-05-10 | 2001-10-23 | Icos Corporation | N-cinnamoyl derivatives of beta-carboline |
US6821978B2 (en) | 2000-09-19 | 2004-11-23 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
US7268141B2 (en) | 2000-09-19 | 2007-09-11 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
US7531544B2 (en) | 2000-09-19 | 2009-05-12 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
US6943171B2 (en) | 2001-11-09 | 2005-09-13 | Schering Corporation | Polycyclic guanine derivative phosphodiesterase V inhibitors |
WO2011023287A1 (en) * | 2009-08-27 | 2011-03-03 | Merck Patent Gmbh | Use of faa and its derivatives in cosmetics and dermatology |
Also Published As
Publication number | Publication date |
---|---|
IT1217190B (it) | 1990-03-14 |
HUT53804A (en) | 1990-12-28 |
HU892651D0 (en) | 1990-11-28 |
IT8820299A0 (it) | 1988-04-22 |
AU3438289A (en) | 1989-11-24 |
JPH02504146A (ja) | 1990-11-29 |
HU202754B (en) | 1991-04-29 |
EP0374210A1 (en) | 1990-06-27 |
KR900700098A (ko) | 1990-08-11 |
ZA892911B (en) | 1989-12-27 |
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