Evaluation of the toxic and teratogenic potential of the anticonvulsant drug 4-hydroxy, 4-ethyl, 4-phenylbutyramide in mice

Abstract

The toxicity profiles of the phenyl alcohol amides: 4-hydroxy, 4-ethyl, 4-phenylbutyramide (HEPB) and two lower homologous: 3-hydroxy, 3-ethyl, 3-phenylpropionamide (HEPP) and 2-hydroxy, 2-ethyl, 2-phenylacetamide (HEPA) were studied in mice. TD50 value was determined by oral administration and LD50 by oral and intraperitoneal routes. The results indicate that HEPP is less toxic than the others, both of which had very similar toxicity. Furthermore, the teratogenic potential of HEPB was investigated in mice after oral administration. The compound was administered on days 6-15 of gestation at doses of 0, 5, 25, 50 or 100 mg/kg of weight. On day 17 of pregnancy the mice were sacrificed and the pups examined. An increase of body weight in both mothers and fetuses was observed at 25 and 50 mg/kg and a decrease was found in mothers receiving 100 mg/kg, as a sign of maternal toxicity. Considering the litter data, embryotoxicity and fetotoxicity were only shown at the highest dose. However, the HEPB treatment did not result in malformations of live fetuses or resorptions when the implantations were considered as the individual entity.