Abstract

PIP: It is demonstrated that for rats N,N'-bis(dischloroacetyl)-1,8-octamethylenediamine (Win 18,446) is a highly efficient embryocidal N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine It was previously used to supress spermatogenesis in man and other mammals. In the initial rat studies, a fixed dosage of Win 18,446 was administered daily from Day 3 to Day 21. With dosages equal to or greater than 100 mg per day all the implants are resorbed although the implantation sites are clearly visible. At a dose of 50 mg per day 90% of the embryos are resorbed; the remainder being alive but deformed. It was determined that although the drug is most effective when administered at Days 10 through 11, a longer schedule that includes these 2 days is not harmful to the mother. The optimal dosage is 200 mg. A mechanism is proposed involving mitochondrial function and replication to explain the action of this drug in the inhibition of embryonic development as well as the suppression of spermatogenesis.