Reproductive, teratogenic, perinatal and postnatal studies with cyclazocine

Abstract

Cyclazocine, a mixed narcotic agonist-antagonist, was evaluated for teratogenic effects in rats and rabbits and for effects on reproductive performance, perinatal and postnatal development in rats. To evaluate teratogenic effects, Charles River albino rats were treated orally from days 6 through 15 of gestation with 3, 10, or 30 mg/kg/day of cyclazocine; New Zealand rabbits were dosed orally from days 6 through 18 of gestation with 1, 3, or 10 mg/kg/day. Rats and rabbits were sacrificed on day 20 or day 29 of gestation, respectively. Numbers of implantation sites, resorption sites, corpora lutea, and viable fetuses, as well as external, internal, and skeletal abnormalities were similar in test and control groups. No dose-related, external, internal or skeletal abnormalities were found in the offspring of either species. To evaluate effects on fertility and general reproductive performance, male or female rats were dosed orally for either 63 or 14 days, respectively, prior to mating with 3, 10, or 30 mg/kg/day. Dosing continued until day 14 of gestation for one-half of the females or after weaning for the other half. Control and treated groups displayed comparable food consumption values, behavior, mating, and fertility indices. To evaluate perinatal and postnatal effects, pregnant female rats were treated from day 15 of gestation throughout lactation. No untoward, drug-related effects were observed in any of the groups. Moreover, when the pups of the high-dose drug group were cross-fostered with control pups, no noticeable drug-related effects were apparent.