RMI 12,936 and pseudopregnancy in rats.

RMI 12,936, when injected subcutaneously at a dose of 2 mg, either on Day 6 of psuedopregnancy (PSP-6) or on PSP-6,7 and 8, shortened the duration of PSP from 12.3 +/- 0.3 (control) to 8.3 +/- 0.1 or 8.7 +/- 0.2 days, respectively. During PSP, plasma progesterone (delta 4P) levels in the peripheral plasma showed a trend of decrease by PSP-9 (52.0 +/- 4.6 on PSP-8 to 42.3 +/- 3.1 ng/ml on PSP-9). Administration of RMI 12,936 on PSP-6 resulted in a significant decrease in delta 4P and pregnenolone (delta 5P) within 24 hr after treatment but caused no apparent changes in 20 alpha-dihydroprogesterone (20 alpha-DHP) levels. However, a significant decrease of delta 4P/20 alpha DHP ratio was encountered 24 hr after RMI 12,936 treatment. The persistent occurrence of proestrous smear after PSP termination, but absence of estrous vaginal cytology, might be attributed to the slight estrogenicity of RMI 12,936. After the premature termination of pseudopregnancy induced by RMI 12,936, the female rats were sexually receptive for at least 3 weeks but failed to conceive, suggesting that this compound has a prolonged contraceptive effect.