1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (DICA), an exfoliative antispermatogenic agent in the rat.

The oral administration of 50 mg DICA/kg at nine weekly or four monthly intervals produced partially reversible infertility in male rats as judged by the results of serial mating and testicular histology. Oral 500 mg DICA/kg doses administered at the same intervals produced permanent sterility. Single oral doses of 50 or 500 mg DICA/kg elevated mean FSH concentrations on days 2, 3, and 7 but did not affect LH or testosterone. Mean plasma concentration peaked at 74 micrograms/ml 4 hr after a 50 mg/kg dose of uniformly tritiated DICA; 24 hr later, it had declined rapidly to 5.5 micrograms/ml. The drug did not have a strong affinity for any tissue studied including the testis. DICA-induced exfoliation of immature germ cells was first observed 4 hr after administration and led to significantly reduced testis weights by day 2. Neither single doses of 10--250 mg DICA/kg nor five daily doses of 10--100 mg DICA/kg reduced seminal vesicle, ventral prostate, or body weights of male rats. Chronic weekly DICA administration did reduce mean seminal vesicle weight. These studies have shown that DICA is an effective, partially reversible antifertility agent that directly affects the rat testis.