Pharmacology of an antiandrogen, anandron, used as an adjuvant therapy in the treatment of prostate cancer
| Autor: | Martine Moguilewsky, Colette Tournemine, Jean Fiet, Jean-Pierre Raynaud |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Male
Receptors Steroid medicine.medical_specialty medicine.drug_class Receptors Cell Surface Pharmacology Imidazolidines Antiandrogen Buserelin Biochemistry Flutamide chemistry.chemical_compound Endocrinology Internal medicine medicine Animals Humans Testosterone Diethylstilbestrol business.industry Imidazoles Prostate Prostatic Neoplasms Cyproterone acetate Androgen Antagonists Organ Size Androgen Rats Kinetics chemistry Receptors Androgen Megestrol acetate business Hydroxyflutamide Orchiectomy Progestin Receptors LHRH medicine.drug |
| Zdroj: | Journal of Steroid Biochemistry. 24:139-146 |
| ISSN: | 0022-4731 |
| DOI: | 10.1016/0022-4731(86)90043-9 |
| Popis: | To improve the inhibition of prostate cancer growth obtained by surgical or chemical castration (estrogens or LHRH analogs), blockade of the action of residual androgens of adrenal origin has been proposed. Among antiandrogens acting through the androgen receptor (AR), the nonsteroid anandron (RU 23908) has several advantages over available compounds: megestrol acetate and cyproterone acetate, both steroids, bind substantially to other hormone receptors (progestin, gluco- and mineralocorticoid); and anandron binds only to AR. The nonsteroid flutamide is a prodrug converted to the active metabolite, hydroxyflutamide; anandron is well absorbed on oral administration of an active dose and intact compound disappears slowly from plasma. This may explain why, although in vitro anandron interacts very transiently with AR, in vivo a high level of untransformed anandron is present at the receptor site to induce its antiandrogenic activity. Animal experiments confirm that anandron can counteract the effect of adrenal androgens and inhibit the LHRH analog-induced initial increase in androgen ("flare-up"). Thus, in rats castrated either surgically or by buserelin or DES and supplemented with adrenal androgens (since endogenous adrenal secretion is very low in this species compared to man), anandron decreased prostate weight to control levels. The administration of buserelin to intact rats over 15 days resulted in a significant increase in prostate weight between Days 1 and 5. The addition of anandron to the buserelin inhibited this increase and, furthermore, led to a far greater decrease in prostate weight than that due to buserelin alone at 15 days, indicating a synergy of action. |
| Databáze: | OpenAIRE |
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