Compounds for the treatment of female sexual dysfunction

• US 6,734,186 B1
• Filed: 11/08/2000
• Issued: 05/11/2004
• Est. Priority Date: 11/08/1999
• Status: Expired due to Fees

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Wayman, Christopher Peter, Maw, Graham Nigel
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Wells, Lauren Q.
• Application Number:
  US09/708,392
• Time in Patent Office: 1,280 Days
• Field of Search: 514/258, 514/263.1, 544/262, 544/224, 544/242
• US Class Current: 514/263.1
• CPC Class Codes: A01K 2227/107 Rabbit
• CPC Class Codes: A01K 67/027 New or modified breeds of vertebrates
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C12Q 1/44 : involving esterase
• CPC Class Codes: G01N 2500/00 : Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/5088 : of vertebrates
• CPC Class Codes: G01N 33/5308 : for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: G01N 33/689 : related to pregnancy or the gonads
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere

Abstract

A method of treating a female suffering from FSD, in particular FSAD, is described. The method comprises delivering to the female an agent that is capable of potentiating cAMP in the sexual genitalia; wherein the agent is in an amount to cause potentiation of cAMP in the sexual genitalia of the female. The agent may be admixed with a pharmaceutically acceptable carrier, diluent or excipient.

Claims

1. A method for treating female sexual arousal disorder comprising the step of orally delivering to a female suffering from female sexual arousal disorder an agent in an amount to cause potentiation of cAMP in the sexual genitalia of the female;

wherein the agent is optionally admixed with a pharmaceutically acceptable carrier, diluent or excipient, and the agent a phosphodiesterase 2 inhibitor.

2. The method according to claim 1 wherein the agent is a mediator of genital vasorelaxation.

3. The method according to claim 1 or 2 wherein said cAMP is endogenous cAMP.

4. The method according to claim 1 or 2 wherein the agent is delivered before or during sexual stimulation.

5. The method according to claim 2 wherein the agent is a mediator of vaginal or clitoral vasorelaxation.

6. A method for treating female sexual arousal disorder comprising the step of orally delivering to a female suffering from female sexual arousal disorder a phosphodiesterase 2 inhibitor in an amount to cause potentiation of cAMP in the sexual genitalia of said female;

wherein said phosphodiesterase 2 inhibitor is admixed with a pharmaceutically acceptable carrier, diluent or excipient.

7. The method according to claim 6 wherein said phosphodiesterase 2 inhibitor is a mediator of genital vasorelaxation.

8. The method according to claim 7 wherein said phosphodiesterase 2 inhibitor is a mediator of vaginal or clitoral vasorelaxation.

9. The method according to claim 6 wherein said cAMP is endogenous cAMP.

10. The method according to claim 6 wherein said phosphodiesteras 2 inhibitor is delivered before or during sexual stimulation.

11. A method for treating a female sexual arousal disorder comprising the step of potentiating in vivo cAMP in female sexual genitalia with an orally administered phosphodiesterase inhibitor, wherein said phosphodiesterase inhibitor directly potentiates cAMP according to an assay method comprising the step of determining whether said phosphodiesterase 2 inhibitor directly potentiates cAMP;

wherein a potentiation of cAMP in the presence of said inhibitor is indicative that said inhibitor is useful in the treatment of said female sexual arousal disorder.

12. A method for treating female sexual arousal disorder in a female suffering from female sexual arousal disorder comprising the step of orally delivering to a female suffering from female sexual arousal disorder a therapeutically effective amount of a phosphodiesterase 2 inhibitor, wherein said phosphodiesterase 2 inhibitor is optionally admixed with a pharmaceutically acceptable carrier, diluent or excipient.

13. The method of claim 12 wherein said inhibitor has a K_i value of less than about 100 nM.

14. The method of claim 12 wherein said inhibitor has a K_i value of less than about 75 nM.

15. The method of claim 12 wherein said inhibitor has a K_i value of less than about 50 nM.

16. The method of claim 12 wherein said inhibitor has a K_i value of less than about 25 nM.

17. The method of claim 12 wherein said inhibitor has a K_i value of less than about 20 nM.

18. The method of claim 12 wherein said inhibitor has a K_i value of less than about 15 nM.

19. The method of claim 12 wherein said inhibitor has a k_i value of less than 10 nM.

20. The method of claim 12 wherein said inhibitor has a K_i value of less than about 5 nM.

21. The method of claim 12 wherein said inhibitor has a K_i selective effect on the genitalia of the female.

22. The method of claim 12 wherein in the absence of sexual stimulation said inhibitor has no or a negligible effect in causing an increase in genital blood flow in said female.

23. The method of claim 12 wherein said inhibitor is in an amount to cause potentiation of endogenous cAMP.

24. The method of claim 12 wherein said inhibitor is used in combination with one or more other pharmaceutically active agents.