title: Topical anti-androgenicity of a new 4-azasteroid in the hamster.
abstract: The topical anti-androgenic activity of L-651,580 (methyl 3-oxo-4-methyl-4-aza-5 alpha-androst-1-ene-17 beta-carboxylate) was established in a series of for experiments using castrated male hamsters. During each 21-day experiment, the animals received a daily subcutaneous injection of 40 micrograms testosterone propionate or 20 micrograms dihydrotestosterone propionate. Test compound in 25 microliters of gel was applied daily to the left flank organ. Compounds assayed included L-651,580, WIN 17,665 (17 alpha-propyltestosterone), and SH-434 (17 beta-hydroxy-1 alpha-methyl-17 alpha-propyl-5 alpha-androstan-3-one). Endpoints were flank organ area, sebaceous gland area, and prostate weight. Very similar results were obtained with L-651,580 and WIN 17,665. Daily doses of 0.25 mg or more of either compound usually produced a significant reduction in the areas of treated flank organs and sebaceous glands underlying treated flank organs. Neither compound caused significant changes in the area of the contralateral flank organs and sebaceous glands, which indicated they possess little or no systemic activity at topically effective treatment levels. In direct comparisons, SH-434 was less anti-androgenic than L-651,580 or WIN 17,665, although in one experiment, 0.5 mg/d of SH-434 significantly reduced the area of treated flank organs and sebaceous glands. Neither WIN 17,665 nor SH-434 caused a change in prostate weight; however, in one of four tests, a significant decrease was induced by the 0.5 mg/d level of L-651,580. The results of these experiments show that the topical anti-androgenicity of L-651,580 compares very favorably with that of WIN 17,665 and SH-434. They also indicate that the topical administration of effective dosage levels of L-651,580 causes few, if any, systemic effects.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey.
authors.forename: J R
authors.initials: JR
authors.lastname: Brooks
authors.forename: R L
authors.initials: RL
authors.lastname: Primka
authors.forename: C
authors.initials: C
authors.lastname: Berman
authors.forename: D A
authors.initials: DA
authors.lastname: Krupa
authors.forename: G F
authors.initials: GF
authors.lastname: Reynolds
authors.forename: G H
authors.initials: GH
authors.lastname: Rasmusson
mesh_terms: D000287:Administration, Topical; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000736:Androstenes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008655:Mesterolone / Q000031:analogs & derivatives / Q000494:pharmacology; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D012627:Sebaceous Glands / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000726:Androgen Antagonists; D000736:Androstenes; D013196:Dihydrotestosterone; D008655:Mesterolone; C072892:L 651580; D013739:Testosterone; C022964:topterone; C041614:17-propylmesterolone; C030445:dihydrotestosterone propionate