Teratological evaluation of a novel antiabortifacient, dibenzyloxyindanpropionic acid. II. Postnatal morphological and behavioral development.

Abstract

Dibenzyloxyindanpropionic acid (DIPA) is an antiabortifacient prostaglandin F2 alpha antagonist. Significant protection against prostaglandin F2 alpha-induced abortion in Charles River CD-1 mice is afforded by 50 mg/kg DIPA, administered intramuscularly twice daily from day-15 of gestation, two days prior to prostaglandin F2 alpha challenge. Furthermore, treatment of CD-1 mice with 50 mg/kg DIPA intramuscularly daily throughout gestation or with 50 or 200 mg/kg twice daily only on day-15 of pregnancy, revealed no structural teratological effects nor histopathological anomalies in the offspring. The present behavioral teratological investigation demonstrates that prenatal treatment of CD-1 mice with 50 mg/kg DIPA intramuscularly daily throughout gestation does not adversely affect postnatal morphological development (offspring viability; weight gain; timing of bilateral pinna detachment, eye opening, eruption of mandibular and maxillary incisors, appearance of mamillary ridges, vaginal opening, testicular descent, and appearance of downy fur), postnatal behavioral development (vocalization; auditory startle reflex; corneal reflex; righting reflex and subsequent air righting; cliff avoidance; limb placing response and grip strength; motor coordination; olfactory orientation; locomotion; motor activity; homing instinct; and acquisition and retention of an active avoidance task), or fertility of the progeny. It is concluded that DIPA is an effective and safe antiabortifacient in mice at the doses tested.