Σπύρος
Μέλος του προσωπικού
Αυτό είναι ένα γαλλικό φάρμακο-δεν έχει ακόμα εγκριθεί από το FDA- το οποίο έχει αποδειχθεί ότι είναι ένα πολύ αποτελεσματικό τοπικό αντιανδρογόννο. Η εταιρεία που παρασκευάζει το φάρμακο έχει κλείσει τις δερματολογικές υπηρεσίες της και δεν υπάρχει πλέον επιδίωξη νέων φαρμάκων από τη υπηρεσία αυτή, συμπεριλαμβανομένου και του RU58841. Είναι άγνωστο αν θα έχουν άδεια για την επεξεργασία του σε άλλες εταιρείες.
1.Inhibition of hair growth by testosterone in the presence of dermal papilla cells from the frontal bald scalp of the postpubertal stumptailed macaque.
Author: Obana N; Chang C; Uno H;
Issue/Part/Supplement: 1 Volume Issue: 138 Pagination: 356-61
MESH Headings: Alopecia*; Animal; Cell Division*; Cells, Cultured*; Female; Hair*; Imidazoles*; Macaca*; Male; Nitriles*; Skin*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Testosterone*; -PG-;
Journal Title Code: EGZ Publication Type: JOURNAL ARTICLE
Date of Entry: 970123N Entry Month: 9703
Country: UNITED STATES Index Priority: 1
Language: Eng Unique Identifier: 97131967
Unique Identifier: 97131967 ISSN: 0013-7227
Abstract: Hair-follicle regression in the bald scalps of stumptailed macaques develops after puberty, which corresponds to an elevation of serum testosterone and dihydrotestosterone. Using the cultured cells from the pre- and postpubertal macaques, we examined the role of dermal papilla cells in testosterone-induced inhibition of outer root sheath cell proliferation. Testosterone showed no effects on proliferation of either dermal papilla cells or outer root sheath cells cultured alone. Testosterone-induced inhibition of outer root sheath cell proliferation occurred only in coculture with dermal papilla cells derived from the bald scalps of adult macaques but not with dermal papilla cells from the hairy occipital scalps of adult macaques or the prebald frontal scalps of juvenile macaques. Furthermore, RU 58841, an androgen receptor blocker, antagonized this testosterone-elicited inhibition. Together our data indicate that the inhibitory effect of testosterone on proliferation of epithelial cells is age dependent, and androgen may play an essential role in hair growth either by inducing repressor(s) from dermal papilla cells, which may then inhibit the growth of epithelial cells of the hair follicle, or by inducing growth factor(s) from dermal papilla cells, which, in turn, may trigger the induction of some repressors in epithelial cells, thereby inhibiting the epithelial cell growth. Our animal studies also showed that RU 58841 has a dramatic effect on hair regrowth in the bald frontal scalp of the stumptailed macaque, which may further support our in vitro culture studies showing that antiandrogens can antagonize testosterone-elicited hair growth. In summary, our studies may provide a model for further isolation of androgen-regulated repressor(s)/growth factors, which may help control hair growth and baldness
2. Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in the rat: relation of their systemic activity to the formation of a common metabolite.
Author
Cousty-Berlin D, Bergaud B, Bruyant MC, Battmann T, Branche C, Philibert D
Address
Centre de Recherches Roussel Uclaf, Romainville, France.
Source
J Steroid Biochem Mol Biol, 51: 1-2, 1994 Oct, 47-55
Abstract
The non-steroidal antiandrogens, RU 58841 and RU 56187 are amongst the most active of a new series of N-substituted aryl hydantoins or thiohydantoins. Their pharmacokinetics and principal metabolic profiles have been evaluated in rat plasma after intravenous administration of a 10 mg/kg dose. Both compounds disappear relatively rapidly from the plasma (elimination half-life of the order of 1 h), but they form a common metabolite, the N-desalkyl derivative, RU 56279, which is eliminated much more slowly. The percentage transformations of each into RU 56279, estimated from the AUCs of the metabolite compared with the AUC obtained after administration of RU 56279 itself, were respectively 1% and 77%. In parallel, their in vivo activity, as well as that of their metabolites, was determined with respect to parameters related to systemic antiandrogenic effects (prostate and seminal vesicle weights). The results showed that: (1) the common metabolite, RU 56279, is clearly antiandrogenic; (2) there appears to be a relationship between the percentage formation of this metabolite and the systemic antiandrogenic activity of the compounds. Thus, the pharmacological profile of RU 58841 which displays a potent local antiandrogenic activity without systemic effects can be related to its very low propensity to form the N-desalkyl metabolite.
3. Local inhibition of sebaceous gland growth by topically applied RU 58841.
Author
Matias JR, Gaillard M
Address
Nova Biosciences, Norrie Point Research Station, Staatsburg, New York 12553, USA.
Source
Ann N Y Acad Sci, 761:1995 Jun 12, 56-65
Abstract
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.
1.Inhibition of hair growth by testosterone in the presence of dermal papilla cells from the frontal bald scalp of the postpubertal stumptailed macaque.
Author: Obana N; Chang C; Uno H;
Issue/Part/Supplement: 1 Volume Issue: 138 Pagination: 356-61
MESH Headings: Alopecia*; Animal; Cell Division*; Cells, Cultured*; Female; Hair*; Imidazoles*; Macaca*; Male; Nitriles*; Skin*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Testosterone*; -PG-;
Journal Title Code: EGZ Publication Type: JOURNAL ARTICLE
Date of Entry: 970123N Entry Month: 9703
Country: UNITED STATES Index Priority: 1
Language: Eng Unique Identifier: 97131967
Unique Identifier: 97131967 ISSN: 0013-7227
Abstract: Hair-follicle regression in the bald scalps of stumptailed macaques develops after puberty, which corresponds to an elevation of serum testosterone and dihydrotestosterone. Using the cultured cells from the pre- and postpubertal macaques, we examined the role of dermal papilla cells in testosterone-induced inhibition of outer root sheath cell proliferation. Testosterone showed no effects on proliferation of either dermal papilla cells or outer root sheath cells cultured alone. Testosterone-induced inhibition of outer root sheath cell proliferation occurred only in coculture with dermal papilla cells derived from the bald scalps of adult macaques but not with dermal papilla cells from the hairy occipital scalps of adult macaques or the prebald frontal scalps of juvenile macaques. Furthermore, RU 58841, an androgen receptor blocker, antagonized this testosterone-elicited inhibition. Together our data indicate that the inhibitory effect of testosterone on proliferation of epithelial cells is age dependent, and androgen may play an essential role in hair growth either by inducing repressor(s) from dermal papilla cells, which may then inhibit the growth of epithelial cells of the hair follicle, or by inducing growth factor(s) from dermal papilla cells, which, in turn, may trigger the induction of some repressors in epithelial cells, thereby inhibiting the epithelial cell growth. Our animal studies also showed that RU 58841 has a dramatic effect on hair regrowth in the bald frontal scalp of the stumptailed macaque, which may further support our in vitro culture studies showing that antiandrogens can antagonize testosterone-elicited hair growth. In summary, our studies may provide a model for further isolation of androgen-regulated repressor(s)/growth factors, which may help control hair growth and baldness
2. Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in the rat: relation of their systemic activity to the formation of a common metabolite.
Author
Cousty-Berlin D, Bergaud B, Bruyant MC, Battmann T, Branche C, Philibert D
Address
Centre de Recherches Roussel Uclaf, Romainville, France.
Source
J Steroid Biochem Mol Biol, 51: 1-2, 1994 Oct, 47-55
Abstract
The non-steroidal antiandrogens, RU 58841 and RU 56187 are amongst the most active of a new series of N-substituted aryl hydantoins or thiohydantoins. Their pharmacokinetics and principal metabolic profiles have been evaluated in rat plasma after intravenous administration of a 10 mg/kg dose. Both compounds disappear relatively rapidly from the plasma (elimination half-life of the order of 1 h), but they form a common metabolite, the N-desalkyl derivative, RU 56279, which is eliminated much more slowly. The percentage transformations of each into RU 56279, estimated from the AUCs of the metabolite compared with the AUC obtained after administration of RU 56279 itself, were respectively 1% and 77%. In parallel, their in vivo activity, as well as that of their metabolites, was determined with respect to parameters related to systemic antiandrogenic effects (prostate and seminal vesicle weights). The results showed that: (1) the common metabolite, RU 56279, is clearly antiandrogenic; (2) there appears to be a relationship between the percentage formation of this metabolite and the systemic antiandrogenic activity of the compounds. Thus, the pharmacological profile of RU 58841 which displays a potent local antiandrogenic activity without systemic effects can be related to its very low propensity to form the N-desalkyl metabolite.
3. Local inhibition of sebaceous gland growth by topically applied RU 58841.
Author
Matias JR, Gaillard M
Address
Nova Biosciences, Norrie Point Research Station, Staatsburg, New York 12553, USA.
Source
Ann N Y Acad Sci, 761:1995 Jun 12, 56-65
Abstract
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.
