Reversible inhibition of spermatogenesis with an indenopyridine (20-438)

30 mg/kg/day 20-438, an Indenopyridine, induced a complete inhibition of spermatogenesis in male dogs within a few days. The dogs did not develop signs of general toxicity. Erection capability and ejaculation were not inhibited, although the sperm number fell to zero. Histologically the seminiferous tubuli were emptied of spermatides and spermatocytes. After drug withdrawal sperm number and histological appearance returned to normal within 8-11 weeks. In rats, single doses of 50 mg/kg or more induced also an arrest of spermatogenesis. The effect was easily detected by the decrease of testes weights. The weight of seminal vesicles remained unchanged. In chronically treated rats, serum-LH and FSH were slightly increased. The compound has similar effects as other substances acting on spermatocytes (AF 1312/TS, Silvestrini et al., 1975; Boris et al., 1974 or WIN 18446, Coulston et al., 1960). The exact mechanism of action (vascular?) has to be elucidated.