The teratogenicity of cyproheptadine in two generations of Wistar rats

Four groups of pregnant Wistar rats were injected intraperitoneally at day 7, 10, 13 or 15 of gestation. Every lot in each group received either 10, 20, 30 or 50 mg/kg cyproheptadine. A fifth group received 2 mg/kg/day of this drug during the entire course of pregnancy. The maximum effect of this drug was found on the 13th and 15th day of gestation. The abnormalities observed in the 21 day old foetuses of the first generation (F1) were found mainly in the brain, kidney, liver as well as in the skull and sternum. Cyproheptadine produced post-natal mortality during the first month from 28.8 to 67.8%. The higher degree of mortality was produced in the rats receiving 2 mg/kg/day. The survivors of this F1 generation were treated in the same way as the parent generation (P). Their descendants (F2) showed similar results. Thus cyproheptadine, in all doses administered, produced signs of toxicity and/or teratogenic effects in rats.