[Reproductive and developmental toxicity studies of montirelin hydrate (4)--Perinatal and postnatal study in rats by intravenous administration].

A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, during the perinatal and lactation periods was conducted in Sprague-Dawley rats. Female rats were given the drug intravenously at dose levels of 0 (control), 0.02, 1 and 50 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. In the 1 and 50 mg/kg groups, food and water consumptions decreased after delivery and the weights of adrenals of the dams increased. In addition, tremor, disappeared within some minutes, was observed during administration period in all dams given 50 mg/kg. Moreover, body weight gain was suppressed after delivery, and the weights of submaxillary glands increased, and the weights of thymus and liver decreased in the dams given 50 mg/kg. The drug did not affect delivery. The drug did not have any adverse effects on the newborn including the number of live newborns, birth index and body weights of live newborn. In the 1 or 50 mg/kg group, body weight gains were suppressed and food consumption decreased in the offspring. The drug did not have any adverse effects on the postnatal development of the offspring such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. These results show that the NOAEL of montirelin hydrate are 0.02 mg/kg for general toxicity in mother animals, 50 mg/kg for reproductive function in mother animals and 0.02 mg/kg for their offspring.