AR 385-95 PDF

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The pharmacologic effects of S -N- 4-cyanotrifluoromethyl-phenyl 3-fluoro, 4-chlorophenoxy hydroxymethyl-propanamide S were characterized in male rats as an animal model of hormonal male contraception. In castrated male rats, the ED50 of S in the prostate and levator ani muscle was 0. In intact male rats treated for up to 10 wk with S and estradiol benzoate EB; necessary to maintain sexual behavior in rats , S showed biphasic effects on androgenic tissues and spermatogenesis by suppressing serum concentrations of LH and FSH.

EB alone showed no effect on spermatogenesis. S increased bone mineral density and lean mass but reduced fat mass in a dose-dependent manner. This is the first study to show that a selective androgen receptor modulator combined with EB is an effective and reversible regimen for hormonal male contraception in rats.

The beneficial effects of S on the muscle, tissue selectivity, and favorable pharmacokinetic properties make it a strong candidate for use in oral male contraception. Chemical structures, AR binding affinity, and in vitro transcriptional activation of C-6 and…. This site needs JavaScript to work properly.

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Figures Figure 1 5 Chemical structures, AR binding affinity,…. Figure 1 13 Chemical structures, AR binding affinity, and in vitro transcriptional activation of C-6 and….

Chemical structures, AR binding affinity, and in vitro transcriptional activation of C-6 and S AR binding affinity was determined using a radioligand competitive assay. The ability of compound of interest to induce AR-mediated transcriptional activation was determined using a cotransfection assay in CV-1 cells. The transcriptional activity induced by each compound at a concentration of 10 n m was reported as the percentage of that observed for 1 n m DHT.

Figure 2 5 A, The androgenic activity and…. Figure 2 13 A, The androgenic activity and anabolic activity of S in castrated male rats. A, The androgenic activity and anabolic activity of S in castrated male rats. S was administrated to animals via daily sc injections for 14 d with doses ranging from 0.

All organ weights were normalized with body weight and presented as the percentage of intact control. B, Dose-response curves of S in castrated male rats. Emax and ED 50 in this figure were obtained by nonlinear least-square regression analysis.

C, The androgenic activity and anabolic activity of S in intact male rats. ORX, Castrated. Figure 3 5 Mean plasma concentration-time profile of…. Figure 3 13 Mean plasma concentration-time profile of S in male rats.

Plasma concentrations of S…. Mean plasma concentration-time profile of S in male rats. Figure 4 5 Testicular sperm concentrations. Each bar…. Figure 4 13 Testicular sperm concentrations. Testicular sperm concentrations. Figure 5 5 The linear correlation between the…. Figure 5 13 The linear correlation between the dose rate of S and body composition percent…. The linear correlation between the dose rate of S and body composition percent of FM and percent of fat free mass.

See this image and copyright information in PMC. Similar articles A selective androgen receptor modulator for hormonal male contraception. Chen J, et al. J Pharmacol Exp Ther. Epub Sep 3. PMID: Nonsteroidal selective androgen receptor modulators enhance female sexual motivation.

Jones A, et al. Epub May 5. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Gao W, et al. Epub Aug Attardi BJ, et al. J Androl. Prolactin influences upon androgen action in male accessory sex organs.

Thomas JA, et al. Adv Sex Horm Res. PMID: Review. Show more similar articles See all similar articles. Cited by 11 articles Selective androgen receptor modulators: the future of androgen therapy?

Christiansen AR, et al. Transl Androl Urol. Liva SG, et al. Epub Jan Solomon ZJ, et al. Sex Med Rev. Epub Nov Pi M, et al. Mol Endocrinol. Epub Oct 6. Nonsteroidal androgen receptor ligands: versatile syntheses and biological data. Varchi G, et al. Show more "Cited by" articles See all "Cited by" articles. Publication types Research Support, N.

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