REPRODUCTION STUDY OF GUANABENZ, A NEW ANTIHYPERTENSIVE AGENT (1) : Fertility Test in Rats

Abstract

Guanabenz (WY-8678) was given to rats to examine its effects on their reproductive ability, dams and their fetuses. The drug was adininistered orally to rats at 30, 15, and 1 mg/kg/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. Male rats were treated for 60 days before mating and the treatment continued through mating. Female rats were treated 14 days before mating and the treatment continued from mating to the 7th day of gestation. The results obtained were as follows. 1. In male rats before mating in the 30, 15, and 5mg/kg groups, the increase of body weight tended to be suppressed, and decrease of food consumption and increase of water intake were found. In female rats before mating in the 30 and 15 mg/kg groups, increase of body weight tended to be repressed, and decrease of food consumption and increase of water intake were found in each group. 2. In the observation of males and females, the drug induced decrease in spontaneous movement, sedation, lacrimation of red exsudate and nebula of the eyeball. 3. In the reproduction test, copulations were confirmed in almost all rats by the second cycle of matings. However, the pregnancy rate tended to decrease a little in the 30 and 15 mg/kg groups. 4. Body weight increase during gestation was not affected by oral administration of 1 mg/kg, but was inhibited dose-dependently by administration of more than 5 mg/kg/day of Guanabenz. Food consumption and water intake tended to increase in drug-treated groups. 5. In the observation of the fetuses, the average number of corpora lutea were decreased in the 15 mg/kg group. The average number of implantations decreased in the 30 and 15 mg/kg groups. The implantation rate decreased in the 30 mg/kg group. No difference was observed in each group on the number of resorptions, the number of live fetuses, and the sex ratio. 6. No difference was observed in each group as to external and visceral malformations. In the skeletal observation, retardation of ossification was observed in the 30 mg/kg group. From these results, it is concluded that Guanabenz shows neither fatal effect nor teratogenic potential on fetuses in rats and the safe dosage level seems to be below 5 mg/kg/day.