Two-generation study of neuroleptic isofloxythepin in rats

The neuroleptic isofloxythepin was tested in a two-generation study in rats in oral doses of 0.1 mg base/kg and 1 mg base/kg. The substance was administered to male and female rats of each generation daily from the weaning onward till the conclusion of the study. The pups of two consecutive generations F0 and F1 were surveilled always in two litters. There were assessed the numbers and body weights of the pups from birth till the weaning, the postnatal developmental milestones, and the results of neuromuscular and locomotor activity tests. In the parents the fertility parameters were followed. --Isofloxythepin at higher dosage, 1 mg/kg, influenced the estrous cycles in the females, prolonging the diestrus stage, but exerted no significant effects upon their fertility and pregnancy. The growth of the offspring of parents treated with isofloxythepin in both generations was slightly retarded. In the F0 generation the pup's mortality increased in the perinatal period. The sedative effect of the neuroleptic manifested itself by a lowering of the locomotor activity. The proved effects of isofloxythepin in the higher dose are mostly connected with the drug's neuroleptic properties. Analogous effects of other substances of this type have been reported in the literature, too. In the course of the study the effects of isofloxythepin did not intensify from the first to the second generation.