[Reproduction study of Guanabenz, a new antihypertensive agent (2) - teratological test in rats]

Guanabenz (WY-8678) was given to pregnant rats to examine its effects on dams, their fetuses, and offspring. The drug was administered orally to rats at 15, 5 and 1 mg/kg/day from the 7th days of gestation. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg, and a control experiment where only the vehicle was administered was also conducted. The results obtained were as follows. 1. In the observation of the dams, the increase of body weight tended to be repressed in the 15 mg/kg group, and body weight decreased in the 30 mg/kg group. 2. The drug produced decreased spontaneous movement, sedation, and lacrimation of red exudate in dams. 3. Half of the 30 mg/kg group had a resorption, but there were no remarkable effects on length of gestation and nursing in the nursing group. 4. The weight of the thymus decreased dose-dependency. 5. No difference was observed in each group in the number of corpora lutea, the number of resorptions, the number of live fetuses, sex ratio, and mean placental weight of the fetuses. The mean body weight of the fetuses decreased in the 30 and among 15 mg/kg groups. 6. In observation of the fetuses, no difference was observed among groups regarding external and visceral malformations. In the skeletal observation, retardation of ossification of the forelimb and hind limb was observed in the 30 and 15 mg/kg groups, and retardation of ossification of the sternebra was observed in the 30 mg/kg group. 7. In observation of the offspring, the number of implantations, the number of live fetuses, delivery rate, and viability rate decrease in the 30 mg/kg group. No difference was observed among groups as to postnatal development symptoms, the faculties of sensation, and emotion. From these results, it is conducted that Guanabenz has no teratogenic potential in rats and the safe dosage levels seems to be below 5 mg/kg/day.