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TZP-4238 is a new potent, orally active steroidal antiandrogen. Antiandrogenic activity and endocrinological profile of TZP-4238 were investigated in rats, except that progestational activity was determined in rabbits. TZP-4238 suppressed the testosterone propionate-induced increases in the weights of the ventral prostate, seminal vesicle and levator ani in castrated immature male rats. TZP-4238 also decreased the weights of the ventral prostate, seminal vesicle and levator ani in intact adult male rats, but did not affect the weight of the testis or the serum concentrations of luteinizing hormone and testosterone. TZP-4238 did not have such an inhibitory effect on the weight of the adrenal gland as seen in other steroidal antiandrogens. It exhibited potent progestational activity. Although TZP-4238 did not exert androgenic or estrogenic activity, it had weak antiestrogenic activity. These results suggest that TZP-4238 exerts an antiandrogenic effect on the prostate without any compensatory change in the serum concentration of luteinizing hormone or testosterone in rats, and it is a useful drug for the treatment of androgen-dependent diseases such as prostatic hypertrophy and prostatic cancer.

Antiandrogenic Activity and Endocrinological Profile of a Novel Antiandrogen, TZP-4238, in the Rat.