[Reproductive and developmental toxicity studies of buspirone hydrochloride (II)--Oral administration to rats during perinatal and lactation periods].
Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 20 of postpartum at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at buspirone 12 mg/kg and higher. 2. Brain and adrenal weights were increased in F0 dams at buspirone 12 mg/kg and higher. Besides, lung and pituitary weights were augmented in F0 dams at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the increased number of stillbirths in F1 neonates. 4. Buspirone 75 mg/kg lowered the viability of newborns (F1) on postnatal day 3 and prolonged the days required for pinnae detachment, presence of abdominal hair and eye opening in offspring (F1), but failed to function their learning ability, motility, motor activity or emotional development. 5. Body weight gains were depressed in both male and female F1 rats at buspirone 12 mg/kg and higher. Food consumption was also decreased in both sexes at the same dose levels. 6. Heart weights were decreased in female F1 rats after mating at buspirone 12 mg/kg and higher. Further, buspirone 75 mg/kg brought a suppression of brain weights at 10 weeks of age in male and female F1 rats, but failed to affect their reproductive ability. 7. F2 neonates derived from F1 rats whose dams had ever received buspirone during the perinatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.
Kai
S
S
Drug Safety Research Department, Bristol-Myers Research Institute, Ltd., Aichi, Japan.
Kohmura
H
H
Ishikawa
K
K
Ohta
S
S
Kuroyanagi
K
K
Kawano
S
S
Kadota
T
T
Chikazawa
H
H
Kondo
H
H
Takahashi
N
N
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects; D002065:Buspirone / Q000008:administration & dosage / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D006321:Heart / Q000187:drug effects; D007774:Lactation; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
D002065:Buspirone