dinoprost and 2-n-butyl-3-(dimethylamino)-5-6-methylenedioxyindene

Calcium channel blockers have been advocated as potential therapeutic agents in the management of premature labor. In the present study, the class of intracellular calcium antagonistic methylenedioxyindenes (MDIs) was investigated for potential antiabortifacient activity in mice. Pretreatment of pregnant mice from day 15 of gestation with the MDIs did not afford protection against the abortifacient effect of prostaglandin F2alpha administered from day 17 of gestation. The MDIs demonstrated embryotoxic and fetotoxic activity as shown by a significant increase in the incidence of resorptions and stillbirths. Similar embryotoxicity was previously reported for the calcium channel blockers. It appears doubtful that any of the calcium antagonists so far examined will be clinically useful in the management of premature labor.. 2 intracellular calcium antagonists with weak membrane calcium channel blocking activity were tested for antiabortifacient and embryotoxic effects in mice. The compounds were 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene (pr-MDI) and cis-2-n-butyl-3-dimethylamino-5,6-methylenedioxindan (cis-H-bu-MDI). Charles River CD-1 mice treated intramuscularly with saline (controls), or Pgf2alpha twice daily to induce premature abortion starting on day 17 of gestation, with 15 or 25 mg/kg cis-H-bu-MDI. or 70 mg/kg/pr-MDI. the LD50 for cis-H-bu-MDI was 75 mg/kg (single intramuscular dose). The compounds had no effect on premature delivery. They significantly decreased numbers of live-born pups, however, counted as the difference between implantation sites and recovered live or stillborn pups. There were no malformations, maternal toxicity or detrimental effects of survival or term-born progeny. These calcium antagonists appear to be of no value in the management of premature labor.

Topics: Abortifacient Agents; Abortion, Spontaneous; Animals; Dinoprost; Female; Fetal Resorption; Indenes; Mice; Pregnancy; Prostaglandins F