Testicular toxicity of a novel 1,4-benzodiazepine (SC-32855) in rats and dogs.
SC-32855, a novel 1,4-benzodiazepine, was administered orally to adult male Beagle dogs (75 mg/kg/day for 10 days) and rats (550 mg/kg/day for 28 days). In both species, SC-32855 caused arrest of spermatogenesis and degeneration of the germinal epithelium, however, it had no effect on Sertoli or Leydig cells. There were no meaningful effects on the weights of the testis, epididymis or prostate in either species. Mean serum luteinizing hormone concentrations in dogs, which were 1.6 +/- 0.2 and 1.5 +/- 0.5 ng/ml prior to dosing, and 3.9 +/- 1.1 and 2.3 +/- 0.5 ng/ml after dosing for the control and treatment groups, respectively, were not significantly changed. Mean serum testosterone concentrations in dogs, which were 1.11 +/- 0.13 and 0.95 +/- 0.10 ng/ml prior to dosing, and 1.05 +/- 0.15 and 1.17 +/- 0.16 ng/ml after dosing for the control and treatment groups, respectively, were also not significantly changed. Further, SC-32855 in vitro did not inhibit the synthesis of testosterone in testicular microsomes isolated from normal rats or dogs. These data indicate that SC-32855 causes testicular damage, which is not secondary to decreased testosterone.
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013045:Species Specificity; D013733:Testicular Diseases / Q000139:chemically induced* / Q000473:pathology; D013737:Testis / Q000473:pathology; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood; D013997:Time Factors
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D013739:Testosterone; C035734:SC 32855; D007986:Luteinizing Hormone