EP0374210A1 - Flevoxate and derivatives for erectile dysfunctions - Google Patents

Flevoxate and derivatives for erectile dysfunctions

Info

Publication number
EP0374210A1
EP0374210A1 EP89904810A EP89904810A EP0374210A1 EP 0374210 A1 EP0374210 A1 EP 0374210A1 EP 89904810 A EP89904810 A EP 89904810A EP 89904810 A EP89904810 A EP 89904810A EP 0374210 A1 EP0374210 A1 EP 0374210A1
Authority
EP
European Patent Office
Prior art keywords
methylflavon
treatment
erectile
erectile dysfunctions
pharmaceutically acceptable
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP89904810A
Other languages
German (de)
English (en)
French (fr)
Inventor
Ralf Ruffmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Recordati SA
Original Assignee
Recordati SA
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 Recordati SA filed Critical Recordati SA
Publication of EP0374210A1 publication Critical patent/EP0374210A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/02Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs 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)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP89904810A 1988-04-22 1989-04-19 Flevoxate and derivatives for erectile dysfunctions Withdrawn EP0374210A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT2029988 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
EP0374210A1 true EP0374210A1 (en) 1990-06-27

Family

ID=11165532

Family Applications (1)

Application Number Title Priority Date Filing Date
EP89904810A Withdrawn EP0374210A1 (en) 1988-04-22 1989-04-19 Flevoxate and derivatives for erectile dysfunctions

Country Status (8)

Country Link
EP (1) EP0374210A1 (hu)
JP (1) JPH02504146A (hu)
KR (1) KR900700098A (hu)
AU (1) AU3438289A (hu)
HU (1) HU202754B (hu)
IT (1) IT1217190B (hu)
WO (1) WO1989010123A1 (hu)
ZA (1) ZA892911B (hu)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9301192D0 (en) 1993-06-09 1993-06-09 Trott Francis W Flower shaped mechanised table
US6143746A (en) * 1994-01-21 2000-11-07 Icos Corporation Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use
GB9514465D0 (en) * 1995-07-14 1995-09-13 Glaxo Lab Sa Chemical compounds
US5503843A (en) * 1994-04-22 1996-04-02 Flora Inc. Transdermal delivery of alpha adrenoceptor blocking agents
GB9423911D0 (en) 1994-11-26 1995-01-11 Pfizer Ltd Therapeutic agents
GB9423910D0 (en) 1994-11-26 1995-01-11 Pfizer Ltd Therapeutic agents
GB9514473D0 (en) * 1995-07-14 1995-09-13 Glaxo Lab Sa Chemical compounds
GB9514464D0 (en) 1995-07-14 1995-09-13 Glaxo Lab Sa Medicaments
SK154498A3 (en) * 1996-05-10 2000-01-18 Icos Corp Carboline derivatives, process for the preparation thereof, pharmaceutical compositions containing same and use of mentioned derivatives as drugs
US6821978B2 (en) 2000-09-19 2004-11-23 Schering Corporation Xanthine phosphodiesterase V inhibitors
WO2003042216A1 (en) 2001-11-09 2003-05-22 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

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0266968A3 (en) * 1986-11-03 1988-08-24 Gérard G. Cohen Gelled ointment of vasodilating agent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8910123A1 *

Also Published As

Publication number Publication date
KR900700098A (ko) 1990-08-11
HUT53804A (en) 1990-12-28
HU892651D0 (en) 1990-11-28
AU3438289A (en) 1989-11-24
WO1989010123A1 (en) 1989-11-02
ZA892911B (en) 1989-12-27
IT1217190B (it) 1990-03-14
JPH02504146A (ja) 1990-11-29
HU202754B (en) 1991-04-29
IT8820299A0 (it) 1988-04-22

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Legal Events

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