Local inhibition of sebaceous gland growth by topically applied RU 58841.
The biological activity of a series of nonsteroidal, pure androgen receptor inhibitors was compared using the Syrian hamster ear skin sebaceous gland model. RU 58841, RU 56187, RU 38882 and cyproterone acetate were applied topically for 4 weeks on the ventral ear pinna of sexually mature male Syrian hamsters. Their order of efficacy was as follows: RU 58841 > RU 56187 > RU 38882 > cyproterone acetate. Maximal reduction of 60% in the size of the sebaceous glands was observed in hamsters treated with RU 58841 at a dose of 10 micrograms per day. This degree of inhibition occurred without any systemic side effects as shown by the absence of inhibition on the contralateral untreated ear pinna. Longer treatment did not produce greater inhibition since extending the treatment period from 4 weeks to 12 weeks showed similar data. The effect of RU 58841 was reversible since the inhibited sebaceous glands returned to normal size within 4 weeks after the cessation of the topical applications. The potent localized inhibition of sebaceous glands by RU 58841 demonstrates the excellent potential of this compound as a topical drug for the treatment of acne and other androgen-mediated disorders.
Matias
J R
JR
Nova Biosciences, Norrie Point Research Station, Staatsburg, New York 12553, USA.
Gaillard
M
M
D000287:Administration, Topical; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D017373:Cyproterone Acetate / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004423:Ear; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007192:Indenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008954:Models, Biological; D009570:Nitriles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012627:Sebaceous Glands / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D013997:Time Factors
D000726:Androgen Antagonists; D007093:Imidazoles; D007192:Indenes; D009570:Nitriles; C090226:4-(3,4,4-trimethyl-5-oxo-2-thioxo-1-imidazolidinyl)-2-(trifluoromethyl)benzonitrile; C086458:RU 58841; D017373:Cyproterone Acetate; C042352:RU 38882