Pharmacodynamics 17α-Allyl-19-nortestosterone, also known as 3-ketoallylestrenol, the active form of<unk> . Progestogenic and off-target activities<unk>  is a progestogen, or an agonist of the progesterone receptor (PR). It is lacking the keto group at the C3 position (part of the important 3-keto-4-ene structure) that is common in progestogens and is considered to be necessary for activity, and in relation to this, is thought to be a prodrug of 17α-allyl-19-nortestosterone (3-ketoallylestrenol).<unk>  is a far less potent progestogen than many other 19-nortestosterone derivatives. The effective ovulation-inhibiting or contraceptive dosage of<unk>  in women has been studied, albeit limitedly. At 20 mg/day<unk> , ovulation occurred in 50% of 6 cycles, and at 25 mg/day, ovulation occurred in 0% of 3 cycles. The total endometrial transformation dosage of<unk>  in women across the cycle is 150 to 250 mg. Unlike virtually all other 19-nortestosterone derivatives,<unk>  is reported to be a pure progestogen and hence to be devoid of androgenic, estrogenic, and glucocorticoid activity. As such, it appears to have properties more similar to those of natural progesterone. The binding and activity profiles of<unk>  and its major active metabolite at steroid hormone receptors and related proteins have been studied.<unk>  has less than 0.2% of the affinity of ORG-2058 and less than 2% of the affinity of progesterone for the PR. Similarly, it has less than 0.2% of the affinity of testosterone for the androgen receptor (AR), less than 0.2% of the affinity of estradiol for the estrogen receptor (ER), less than 0.2% of the affinity of dexamethasone for the glucocorticoid receptor (GR), and 0.9% of the affinity of testosterone for sex hormone-binding globulin (SHBG). Conversely, its metabolite 17α-allyl-19-nortestosterone has 24% of the affinity of ORG-2058 and 186% of the affinity of progesterone for the PR, 4.5% of the affinity of testosterone for the AR, 9.8% of the affinity of dexamethasone for the GR, and 2.8% of the affinity of testosterone for SHBG, while it similarly has less than 0.2% of the affinity of estradiol for the ER. The affinity of 17α-allyl-19-nortestosterone for the AR was less than that of norethisterone and medroxyprogesterone acetate and its affinity for SHBG was much lower than that of norethisterone. These findings may help to explain the absence of teratogenic effects of<unk>  on the external genitalia of female and male rat fetuses. Relative affinities (%) of<unk>  and metabolites Compound<unk>  0 0 0 0 ? 1 ? 186 5 0 10 ? 3 ? Notes: Values are percentages (%). Reference ligands (100%) were for the , for the , for the , for the , aldosterone for the , for , and cortisol for . Sources: Antigonadotropic effects Testosterone levels with 50 mg/day<unk>  or 50 mg/day chlormadinone acetate orally over 12 weeks in men with benign prostatic hyperplasia. Similarly to other progestogens,<unk>  has potent antigonadotropic effects. It is able to considerably decrease circulating concentrations of luteinizing hormone, testosterone, and dihydrotestosterone in men. At a dosage of 50 mg/day,<unk>  has been found to suppress circulating testosterone levels by 78% in men with BPH. This is about the maximum that progestogens are known to be able to suppress testosterone levels in men. In accordance, the reduction of testosterone and luteinizing hormone levels with<unk>  in men has been found in a study to be equivalent to that of chlormadinone acetate and oxendolone. However, another study found a significantly lower decrease in testosterone levels with 50 mg/day<unk>  relative to 50 mg/day chlormadinone acetate of about 49–52% versus 76–85%, respectively. Animal research suggests that<unk>  produces its beneficial effects in BPH via its antigonadotropic effects and consequent suppression of androgen levels and inhibition of prostate gland growth, similarly to other progestins. Some studies have found that<unk>  is less effective for BPH than chlormadinone acetate but also produces fewer side effects and sexual dysfunction.<unk>  therapy for BPH is associated with a significant decrease in prostate-specific antigen levels, which may mask the detection of prostate cancer. Other activities<unk>  is not a significant 5α-reductase inhibitor. In one study, it showed about 80,000-fold lower potency for inhibition of 5α-reductase in vitro than the established 5α-reductase inhibitor epristeride ( = 11.3 nM for epristeride and 890 μM for<unk> . In another study, there was 70% inhibition of 5α-reductase by<unk>  at a concentration of 60 μM. This difference may have been due to different experimental conditions, but is still much lower than epristeride. Pharmacokinetics Following oral administration, peak levels of<unk>  occur after 2 to 4 hours. The medication shows considerable plasma protein binding. It has relatively low affinity for SHBG, much lower than that of norethisterone.<unk>  is metabolized in the liver, via reduction, hydroxylation, and conjugation. It is known to be a substrate of CYP3A4. It is thought to be a prodrug of 17α-allyl-19-nortestosterone (3-ketoallylestrenol), which, in accordance, is a known active metabolite of<unk> . The biological half-life of<unk>  has been reported to be "several hours" or, presumably in its active form, reportedly about 10 hours. In the blood, unchanged<unk>  accounted for 15 to 40% of radioactivity, an unconjugated metabolite accounted for 4 to 10% of radioactivity, and the rest of the radioactivity corresponded to conjugated metabolites.<unk>  is eliminated mainly in urine, 44% by 24 hours and 67% within 4 days. It is excreted almost completely as conjugates, with 75% of these being sulfate conjugates and 24% being glucuronide conjugates.
Allylestrenol
Lynestrenol
Ethylestrenol
Norethandrolone
Androstanolone
Androstanolone benzoate
Norethisterone
Cloxotestosterone acetate