Synergistic effects on pregnancy-termination activity of DL111-IT in combination with mifepristone.
OBJECTIVE
To clarify the role of DL111-IT when combined with mifepristone (Mif) on termination of early pregnancy.


METHODS
Progesterone receptors (PR) was measured using radioligand assay (RA), and peroxidase-antiperoxidase (PAP) immuno-histochemistry. Decidual cells (DC) were estimated using cell culture and histological examination (HE) (including fetus).


RESULTS
DL111-IT 100 mg.kg-1 i.m., Mif 5 mg.kg-1 i.g., DL111-IT 16 mg.kg-1 i.m. + Mif 1.5 mg.kg-1 i.g. and tea seed oil (TSO) 2 mL.kg-1 i.m. on d 7 of pregnancy in rats, DC and fetus of treated groups were found to be degenerated at 24 h after treatment, at 48 h after treatment, PAP labeling index (%) of uterus PR of 4 groups were 22 +/- 4, 18.7 +/- 2.9, 10.3 +/- 1.2, 52 +/- 15, respectively. Rats i.m. DL111-IT 100 mg.kg-1 24 h after treatment, the quantity of PR decreased by 47% vs that of TSO. The affinity of PR with Mif and progesterone did not change. Cultured human DC were exposed to DL111-IT and Mif 0-50 mg.L-1, alone or combinatively, for 24 h. LD50 (mg.L-1) were: DL111-IT 18.1 (15.1-21.4), Mif 25.0 (23.1-26.9), DL111-IT 5.0 plus Mif 3.5 (1.8-6.5) or Mif 5.0 plus DL111-IT 4.6 (1.1-7.3), respectively.


CONCLUSIONS
DL111-IT enhanced action of Mif on DC, reduced quantity of PR, so the 2 drugs had the synergistic action in termination of early pregnancy.
Yang
B
B
Department of Pharmacology, School of Pharmacy, Zhejiang Medical University, Hangzhou, China.
Fang
R Y
RY
D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology; D000021:Abortifacient Agents, Steroidal / Q000494:pharmacology; D000028:Abortion, Induced; D000818:Animals; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*; D014599:Uterus / Q000378:metabolism
D000020:Abortifacient Agents, Nonsteroidal; D000021:Abortifacient Agents, Steroidal; D011980:Receptors, Progesterone; D014230:Triazoles; D015735:Mifepristone; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole