Teratological experiments with ergotamine in mice, rats, and rabbits

Abstract

Pregnant mice, rats, and rabbits were treated orally with ergotamine during midgestation. In doses that affected maternal weight gain during treatment, ergotamine produced an increase in prenatal mortality in rats and evidence of fetal retardation in all three species. The results are discussed in connection with the vasoconstrictive action of ergotamine. A uterotonic effect may also be involved in the mechanism of action. No specific teratogenic activity was detected in any of the three species.

Ergotism and Photosensitization in Swine Produced by the Combined Ingestion of Claviceps Purpurea Sclerotia and Ammi Majus Seeds

“…Oral administration of EGT tartrate to mice, rats, and rabbits produced smaller fetuses and prenatal mortality in rats. 10 Laboratory findings for the swine on this farm indicate that these swine were exposed to levels of ergot and of ergot alkaloids similar to those previously reported by other investigators to cause embrionary retardation and resorption and perinatal mortality in other animal species. 10,20 Information concerning abortions produced by ergot ingestion or administration seems to indicate a speciesdependent susceptibility to ergot toxicity.…”

“…10 Laboratory findings for the swine on this farm indicate that these swine were exposed to levels of ergot and of ergot alkaloids similar to those previously reported by other investigators to cause embrionary retardation and resorption and perinatal mortality in other animal species. 10,20 Information concerning abortions produced by ergot ingestion or administration seems to indicate a speciesdependent susceptibility to ergot toxicity. Natural and experimental ergotism-related abortions have been observed in cows and sheep, 2,11 but ergot poisoning has not been associated with abortions in sows.…”

“…9 During the same stage of pregnancy, rats, mice, and rabbits given oral EGT showed prenatal mortality and fetal retardation. 10 EGT causes strong vasoconstrictive action, which in this situation may have decreased the placental blood flow, thus explaining the small fetal sizes.…”

Pregnancy Outcome Following Prescription for Sumatriptan

“…Ergotamine, a nonselective serotonin agonist, is considered to be contraindicated in pregnancy, as the drug may lead to increased prenatal mortality, growth retardation, and fetal hypoxia due to a prolonged and marked increase in uterine tone and impaired placental blood flow. [8][9][10][11][12][13][14][15][16][17] Although sumatriptan reacts selectively in brain vessels, the possibility of reactions with placental blood flow and uterotonic activity cannot be ruled out. Feniuk et al did not find that sumatriptan stimulation resulted in uterine contractions in animal models.…”

Acute Studies to Investigate the Mechanism of Action of Caffeine as a Teratogen in Mice

“…Having established day 14 as the sensitive day for caffeine-induced cleft palate, all of the acute studies to investigate its mode of action as a teratogen were carried out on day 14 pregnant mice. Since it is known that vasoactive drugs can induce malformations by reducing uteroplacental blood flow (Robson, Poulson & Sullivan, 1965;Grauwiler & Schon, 1973), and since it is well known that caffeine has pharmacological effects on the cardiovascular system (Rall, 1980), the effect of caffeine on uteroplacental blood flow was studied. Because of the difficulties of using conventional blood flow measuring systems in intact pregnant mice, a radiochromium labelled erythrocyte method was used which has previously been used to demonstrate the uterine vasoconstriction induced by 5-hydroxytryptamine in pregnant mice (Robson & Sullivan, 1966).…”