Abstract
The biological and the pharmacokinetic profiles of 2-(3-ethoxy-phenyl)-5,6-dihydro-s-triazole [5,1-a]isoquinoline (DL 204-IT) were explored in rats and hamsters at different stages of gestation (1st--11th day) after single and multiple (5 days) doses given in different vehicles (oily and aqueous) and by different routes of administration (s.c., i.m., i.v.). The effectiveness of the compound was demonstrated to be dependent on time of gestation, dose and vehicle. DL 204-IT did not show any pre-implantation activity. The optimal time for treatment was found to be immediately after the implantation of blastocysts. Time-course studies demonstrated that the anti-fertility action is slow and progressive with subsequent degeneration and reabsorption (rats and hamsters), or expulsion (only hamsters) of conceptuses. The biological and pharmacokinetic data show that with prolonged presence of the compound at the site of action (the utero-placental complex) lower doses are far more active in interrupting embryonal development than are much higher ones for shorter time periods.