The pharmacological profile of a novel norpregnane progestin (trimegestone)

Trimegestone is a novel norpregnane progestin that is being developed, in c ombination with estradiol, for the treatment of menopausal symptoms. The ph armacological characteristics of trimegestone have been evaluated in both i n vitro and in vivo test systems, and compared with reference progestins. I nteraction with hormonal steroid receptors from animal tissues and with hum an recombinant receptors in vitro has demonstrated that trimegestone has a high specificity and potency for the progesterone receptor, no affinity for the estrogen receptor, and weak affinity for androgen, glucocorticoid and mineralocorticoid receptors. With respect to progestomimetic activity in vi vo, trimegestone was more potent than reference progestins in the endometri al transformation test in the rabbit, preventing the uterotrophic effect of estradiol in the immature mouse bioassay, and had more effect on traumatic deciduoma formation and greater oral antiovulatory activity in the rat. In vivo, trimegestone effectively maintained pregnancy in the rat, but was de void of any uterotrophic activity. Trimegestone showed no androgenic, gluco corticoid, antiglucocorticoid or mineralocorticoid activity, but did show s ome antiandrogenic and antimineralocorticoid activity at higher doses. Admi nistration of trimegestone to ovariectomized rats, in combination with estr adiol, inhibited the uterotrophic effects of estradiol. At doses up to 1 mg /kg intravenously and 30 mg/kg orally, trimegestone was not associated with any unwanted pharmacological effects. Overall, the results show trimegesto ne to have a favorable pharmacological profile with potent progestomimetic activity.