Developmental Toxicity of Amesergide Administered by Gavage to CD Rats and New Zealand White Rabbits

Amesergide is a selective serotonin 5-HT_IC/2 receptor antagonistbeing developed for the treatment of depression. The potentialdevelopmental toxicity of amesergide was evaluated in CD ratsand New Zealand white rabbits. Pregnant rats and rabbits weredosed once daily by gavage on Gestation Days 6–17 and6–18, respectively. Doses for rats were 0, 3, 10, and30 mg/kg; doses for rabbits were 0, 0.2, 2, and 15 mg/kg. Cesareansections were performed on rats and rabbits on Gestation Days20 and 28, respectively. In rats, maternal effects expressedas depression of body weight gain and food consumption wereobserved at the 30 mg/kg dose level. Fetal viability and morphologywere not affected at any dose level. Fetal weight was depressedat the 30 mg/kg dose level. The no-observed-effect level (NOEL)in the rat was 10 mg/kg. In rabbits, maternal effects expressedas a decrease in food consumption occurred at the 2 and 15 mg/kgdose levels; weight gain was depressed at 15 mg/kg. Fetal viability,weight, and morphology were not affected at any dose level.The NOELs for maternal and developmental effects in the rabbitwere 0.2 and 15 mg/kg, respectively.