EXPERIMENTAL PHARMACOLOGIC STUDIES ON THE MALE ANTIFERTILITY AGENT α-CHLOROHYDRIN AND ITS ANALOGUES

The results of pharmacologic experiments on α-chlorohydrin and its analogues are reported in this paper. A prominent antifertility action of α-chlorohydrin has been demonstrated in male rats after a daily oral dose of 5 mg/kg for 5 days. Prologned medication up to 22～25 weeks did not affect the growth curves, sexual behavior, and structures of several important organs. Normal fertility recovered after cessation of the medication. Subacute toxicity tests on male rats and dogs with daily oral dose of 20～25 mg/kg revealed minor pathologic changes in liver cells and cerebellar elements.In our study, α-chlorohydrin probably exerted its antifertility action through mutagenic effect on the sperms, since fertilized ova with signs of early degeneration have been repeatedly found in the Fallopian tubes, indicating the sperms still retained their fertilizing ability.The pseudopregnancy in female rats having non-fertile mating with α-chlorohydrintreated males provided us an ideal model for reproductive physiological studies, these female rats were easily picked up by vaginal, smears, the pseudopregnancy induced being more physiologic than by other means. We have taken advantage of this model in performing deciduoma and egg transfer experiments with unexpected high rate of success.A series of 35 analogues of ’α-chlorohydrin have been screened, further work is still in progress in order to find compounds superior to the parent substance.