[Reproduction study of Guanabenz, a new antihypertensive agent (1) - fertility test in rats]. 1982

K Akatsuka, and T Hashimoto, and K Takeuchi

Guanabenz (WY-8678) was given to rats to examine its effects on their reproductive ability, dams and their fetuses. The drug was administered 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 5 mg/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 exudate 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.

UI MeSH Term Description Entries
D008297 Male Males
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001842 Bone and Bones A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principal cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX. Bone Tissue,Bone and Bone,Bone,Bones,Bones and Bone,Bones and Bone Tissue,Bony Apophyses,Bony Apophysis,Condyle,Apophyses, Bony,Apophysis, Bony,Bone Tissues,Condyles,Tissue, Bone,Tissues, Bone
D004435 Eating The consumption of edible substances. Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes
D005260 Female Females
D005298 Fertility The capacity to conceive or to induce conception. It may refer to either the male or female. Fecundity,Below Replacement Fertility,Differential Fertility,Fecundability,Fertility Determinants,Fertility Incentives,Fertility Preferences,Fertility, Below Replacement,Marital Fertility,Natural Fertility,Subfecundity,World Fertility Survey,Determinant, Fertility,Determinants, Fertility,Fertility Determinant,Fertility Incentive,Fertility Preference,Fertility Survey, World,Fertility Surveys, World,Fertility, Differential,Fertility, Marital,Fertility, Natural,Preference, Fertility,Preferences, Fertility,Survey, World Fertility,Surveys, World Fertility,World Fertility Surveys
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D006143 Guanabenz An alpha-2 selective adrenergic agonist used as an antihypertensive agent. 2,6-Dichlorobenzylideneaminoguanidine,BR-750,Guanabenz Acetate,Guanabenz Monoacetate,WY-8678,Wyeth-Ayerst of Guanabenz Acetate,Wytensin,2,6 Dichlorobenzylideneaminoguanidine,Acetate Wyeth-Ayerst, Guanabenz,Acetate, Guanabenz,BR 750,BR750,Guanabenz Acetate Wyeth-Ayerst,Monoacetate, Guanabenz,WY 8678,WY8678,Wyeth Ayerst of Guanabenz Acetate
D006146 Guanidines A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.

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