RESUMO
The effects of oral ritodrine on artificially induced intra-uterine growth retardation in rats were tested in two animal models. In one model, foetal hypotrophy was induced by reduction of the uterine blood supply on ligating of the left uterine artery. In that experiment no significant inhibition of the foetal hypotrophy could be detected in the ritodrine treated animals, but the corresponding reduction of placental weight was inhibited. In the other model, hypotrophy was induced by hypothermia. Oral ritodrine, given twice daily in a dose of 50 mg/kg from day 7 to day 21 of the pregnancy, antagonized the decrease of the foetal weight produced by hypothermia.
Assuntos
Retardo do Crescimento Fetal/tratamento farmacológico , Propanolaminas/uso terapêutico , Ritodrina/uso terapêutico , Animais , Artérias/fisiologia , Temperatura Baixa , Feminino , Retardo do Crescimento Fetal/etiologia , Ligadura , Tamanho do Órgão/efeitos dos fármacos , Placenta/efeitos dos fármacos , Gravidez , Ratos , Ritodrina/farmacologia , Útero/irrigação sanguíneaRESUMO
PIP: Endocrine effects of 2 new retrosteroids, DU 164 and DU 41 165, in a nimal models and in women are reported. Both retrosteroids exhibited hi gh progestational activity in the rabbit, their potency being 18 times that of the reference standard, chlormadinone acetate (CMA), when administered orally. Both retrosteroids maintained pregnancy in rabbits and rats with a potency of 6 and 11 times that of CMA for DU 41 164 and DU 41 165, respectively. In the pregnancy maintenance tests in rats the effective dose (ED) 50 of DU 41 164 and DU 41 165 was 2000 mcg/kg/day and 290 mcg/kg/day, respectively, whereas CMA could not maintain pregnancy in doses of 50,000 mcg/kg/day. Both retrosteroids were highly active as antifertility agents in rabbits and rats. Their potencies were 80 and 40 times that of CMA in rabbits and 100 and 300 times that of CMA in rats. In ovulation inhibition tests the ED 50 of oral DU 41 164 and DU 41 165 were .5 and .4 mcg/kg in rabbits, whereas the ED 50 of CMA was 40 mcg/kg. The retrosteroids were also more potent than CMA in ovulation inhibition and antiestrogenic activity. High doses of DU 41 165 induced a decrease in adrenal weight and exhibited some antiinflammatory effects. 23 volunteers treated with 50 or 200 mcg of the compounds/day revealed no consistent inhibition of ovulation and of corpus luteum function. Endometrial biopsy specimens obtained on Cycle Days 12-13 during treatment with 200 mcg of either retrosteroid revealed no signs of progestational effect.^ieng
