Effects of carbamazepine on the first ovulation in gonadotropin-primed immature female rats

1 The effects of carbamazepine (CBZ) and its possible mechanisms on the fir st ovulation were investigated in immature female rats. The first ovulation was induced by administration of equine chorionic gonadotropin (eCG) at 08 00 h at 26 days of age. 2 A single s.c. injection of 360 mg kg(-1) CBZ at 1300 h on the first pro-o estrus (day 28) completely inhibited the first ovulation on the morning of day 29. A marked elevation in 13, 14-dihydro-prostaglandin F-2 alpha (13, 1 4H(2)-PGF(2 alpha)) forming capacity, a sensitive indicator of luteinizing hormone (LH) surge, was not detected in the CBZ-treated group at 0800 h on day 29 (72 h after eCG treatment). The elevation in serum LH levels at 57 I t after eCG treatment was not observed in the CBZ-treated group, either. Th e blocking of the first ovulation and 13, 14H-PGF(2 alpha) forming capacity were recovered by an i.p. injection of human CG on day 28 in all animals. 3 However, the first ovulation was not blocked by repeated injections of 36 0 mg kg(-1) CBZ at 1300 h once daily for 3 days (days 26-28). The repeated injections of CBZ caused a great fall (64% decrease) in the serum levels of CBZ at 4 h after the final CBZ injection as compared with the case of a si ngle injection of CBZ and resulted in a delay for 5 h the occurrence of LH surge, which is normally observed around 57 h after eCG injection. 4 A significant increase in the activity of microsomal CBZ catabolism by th e repeated injections of CBZ was quantitatively verified by the HPLC analys is. But, the activity of CBZ metabolism in the single injected-animals show ed almost similar levels to that in the control. 5 The present results demonstrated that a single injection of CBZ blocks th e ovulation by inhibiting LH surge but that the failure of the inhibition o f ovulation by repeated injections of CBZ is due to a decrease in serum CBZ levels mediated through CBZ-induced hepatic enzyme induction.