VERY VERY GOOD ARTICLE. MUST READ…I SWEAR IM ON TO SOMETHING HERE…
Using 3a Androstandiol Gluc. and 5-HT1A agonist for treatment of Male ED and Female ED.
JN PLEASE READ BROTHER, need your input!
The link it below. I pointed a few key paragraphs that I found interesting. Please read the whole article…
LINK: faqs.org/patents/app/20100093680
Abstract:
The invention relates to the field of male and/or female sexual dysfunction. The invention specifically relates to the use of 3-alpha-androstanediol, preferably in combination with a 5-HT1A agonist. Optionally, said 3-alpha-androstanediol and said 5HT1a agonist are further combined with a type 5 phosphodiesterase (PDE5) inhibitor.
[0004]3-alpha-androstanediol is described in U.S. Pat. No. 6,242,436 B1 as an alternative to androgen repletion therapy and for androgen decrease/depletion related problems in humans. The described purpose of this substitution lies in the replenishment of subphysiological serum concentrations of Dihydrotestosterone (DHT) via 3-alpha-androstanediol administration. Also, the mechanism of effect of decreasing androgen decrease/depletion related problems lies in the replenishment of (DHT), according to U.S. Pat. No. 6,242,436 B1. Androgen depletion can decrease sexual motivation. However, decreased sexual motivation is often not caused by abnormal androgen concentrations.
[0006]The present invention discloses that 3-alpha-androstanediol administration will induce increased sexual motivation and increased attention for sexual cues in men with MSD and women with FSD. These 3-alpha-androstanediol administration dependant increases in motivation and attention are independent of prior physiological androgen concentrations; 3-alpha-androstanediol administration will increase sexual motivation and attention for sexual cues in men and women with normal (i.e. physiological) or with subphysiological androgen levels alike.
0011]3-alpha-androstanediol is preferably given in a formulation wherein there is a sharp and rapid increase of 3-alpha-androstanediol in the blood circulation of the subject to whom it is administered. The invention therefore provides a use, wherein the 3-alpha-androstanediol is provided in the form of a sublingual formulation, for example a sublingual formulation comprising cyclodextrins as carrier. Another example of a suitable route of administration is buco-mucosally or intranasally, which can also be performed with the use of a cyclodextrin formulation or other usual excipients, diluents and the like. A typical example of a formulation is given in hydroxypropyl-beta cyclodextrin, but other beta cyclodextrins and other usual excipients, diluents and the like are within the skill of the art for preparing a formulation comprising 3-alpha-androstanediol, which releases essentially all of the 3-alpha-androstanediol within one short burst. Said burst will typically be within a short time interval (for example within 60-120 seconds, more preferably within 60 seconds) upon administration, leading to blood peak levels of 3-alpha-androstanediol about 1-60 minutes later, lasting for at least 180 minutes from time of application.
[0014]In a second embodiment, the invention provides an effective combination of 3-alpha-androstanediol with another compound, i.e. the invention provides use of 3-alpha-androstanediol and a 5-HT1A agonist in the preparation of a medicament for the treatment of sexual dysfunction in men and/or women. In a preferred embodiment, said 3-alpha-androstanediol and said 5-HT1A agonist are released at essentially the same time.
[0015]Preferably, the used 5-HT1A agonist is selective for the 5-HT1A receptor over other 5-HT receptors and the .alpha.-adrenoreceptor and dopamine receptor. Non-limiting xamples of a 5-HT1A agonist are 8-OH-DPAT, Alnespirone, AP-521, Buspar, Buspirone, Dippropyl-5-CT, DU-125530, E6265, Ebalzotan, Eptapirone, Flesinoxan, Flibanserin, Gepirone, Ipsapirone, Lesopitron, LY293284, LY301317, MKC242, R(+)-UH-301, Repinotan, SR57746A, Sunepitron, SUN-N4057, Tandosporine, U-92016A, Urapidil, VML-670, Zalospirone or Zaprasidone.
Experiment 3 3-Alpha-Androstanediol and Flesinoxan in MSD
[0062]efficacy of combined administration of 3-alpha-androstanediol and a 5-HT1A receptor agonist–flesinoxan–on male sexual function in response to erotic film excerpts in men with MSD
[0063]In a double-blind, randomly assigned placebo controlled cross-over design, a group of 16 men with male sexual dysfunction (MSD) will receive [0064]1. 3-alpha-androstanediol (0.5 mg) and flesinoxan (1 mg) [0065]2. 3-alpha-androstanediol (0.5 mg) alone [0066]3. flesinoxan (1 mg) alone [0067]4. placeboon 4 separate experimental days.
[0068]The penile tumescence and rigidity will be measured in response to neutral and erotic film audiovisual stimulation (VSTR), directly after drug administration, and 1 hour after drug administration, directly followed by measurement of vibrotactile stimulation ejaculatory latency time (VTS-ELT) and postejaculatory erectile refractory time. The four experimental days will be separated by (at least) a three-day period. On all drug administrations, subjects will receive one capsule consisting of either flesinoxan or placebo, and one liquid formulation with either 3-alpha-androstanediol or placebo. Both capsule and liquid formulation will be taken at the same time, one hour prior to testing. The effect of sublingual 3-alpha-androstanediol and flesinoxan will overlap due to their similar time lag (0-1 hour).
[0069]Subjects with a history of endocrinological, neurological or psychiatric illness and/or treatment. Standard blood chemistry and hematology tests will be performed. Participants are required not to use alcohol or psychoactive drugs the evening before and the day of experimentation. During period of menstruation, subjects will not be tested.
Experiment 4 3-Alpha-Androstanediol, Flesinoxan and Sildenafil in MSD
[0070]Efficacy of combined administration of 3-alpha-androstanediol, a 5-HT1A receptor agonist–flesinoxan–and a PDE5 inhibitor–sildenafil–on male sexual function in response to erotic film excerpts in men with MSD
[0071]In a double-blind, randomly assigned placebo controlled cross-over design, a group of 16 men with male sexual dysfunction (MSD) will receive [0072]1. 3-alpha-androstanediol (0.5 mg) and flesinoxan (1 mg) and sildenafil (10 mg) [0073]2. 3-alpha-androstanediol (0.5 mg) and flesinoxan (1 mg) [0074]3. flesinoxan (1 mg) and sildenafil (10 mg) [0075]4. 3-alpha-androstanediol (0.5 mg) alone [0076]5. flesinoxan (1 mg) alone [0077]6. placeboon 6 separate experimental days.
[0078]The penile tumescence and rigidity will be measured in response to neutral and erotic film audiovisual stimulation (VSTR), directly after drug administration, and 1 hour after drug administration, directly followed by measurement of vibrotactile stimulation ejaculatory latency time (VTS-ELT) and postejaculatory erectile refractory time. The six experimental days will be separated by (at least) a three-day period. On all drug administrations, subjects will receive one capsule consisting of either flesinoxan, or sildenafil, or sildenafil and flesinoxan or a placebo, and one liquid formulation with either 3-alpha-androstanediol or placebo. Both capsule and liquid formulation will be taken at the same time, one hour prior to testing. The effect of sublingual 3-alpha-androstanediol and flesinoxan will overlap due to their similar time lag (0-1 hour) and will overlap with high sildenafil serum concentrations (Tmax of sildenafil 30-120 min; T1/2=3.5 hours).
[0079]Experiments 3-4 will be preceded by a screening visit. In this screening visit subjects are interviewed and examined by a resident of the department of gynaecology of Flevo Hospital, Almere to diagnose for MSD and to determine eligibility for study participation. Subjects will be asked to fill out a questionnaire; the international index of erectile function questionnaire (IIEF). Weight, height, blood pressure (supine and standing) will be measured. Cardiovascular condition will be tested and ECG checked for significant abnormalities. Participants are required not to use alcohol or psychoactive drugs the evening before and the day of experimentation.