[Reproduction study of Guanabenz, a new antihypertensive agent (3) - perinatal and postnatal test in rats]

Guanabenz (WY-8678) was given to rats to examine its effects on dams and offspring in terms of influence on postnatal development emotion, learning and reproductive ability. The drug was administered orally to rats at 15, 8, 5, 2 and 1 mg/kg/day from the 17th day of gestation to the 21st post-partum day. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg and a control experiment where only vehicle was administered was also conducted. The results obtained were as follows. 1. In observation of the dams, increase in body weight tended to be repressed after administration in the 8 mg/kg group, and in the 15 mg/kg group body weight decreased. Food consumption and water intake tended to be suppressed in the 15 mg/kg group. During nursing, changes of body weight, food consumption and water intake were not influenced by Guanabenz in each group. 2. The drug produced sedation, abnormal walking, decrease in a reflex test and lacrimation of red exudate in dams. 3. In the 15 mg/kg group, the length of gestation was prolonged. Furthermore, abnormal delivery and nursing were observed, and in one-third of dams in the 8 mg/kg group and in all dams of 15 mg/kg group, the still-birth of all offspring was observed. No difference was observed among groups as to the organ weights at weaning. 4. In observation of the offspring, differences were observed in the viability rate and the weaning rate. No difference was observed among groups as to the viability rate, changes of body weight, postnatal development, and behavioral development on the 7th day. No differences were observed in each group regarding emotion, motion, perception and learning. 5. No difference was observed among groups in the reproduction test. As to symptoms seen in gestation, the dams and fetuses were not influenced by dosage of Guanabenz. From these results, the safe dose level seems to be below 5 mg/kg/day.