Anti-implantation activity of H₂receptor blockers and meloxicam, a COX-inhibitor, in albino Wistar rats

OBJECTIVE: To evaluate the anti-implantation activity of H(2) receptor blockers ranitidine and famotidine, and Cox-inhibitor meloxicam, alone and in combination, considering the role of histamine and prostaglandins in implantation. METHOD: The drugs were administered orally to female albino Wistar rats at different dose levels for 1 to 7 days, immediately after confirming copulation by observing sperm in the vaginal smear. A laparotomy was done on the 10th day of pregnancy, the implants and corpora lutea were counted, and the pre- and post implantation losses determined. The mast cell stabilising activity was studied using both in vitro and in vivo methods. RESULTS: Ranitidine 70 mg/kg (75.41%; p < 0.01), and famotidine 80 mg/kg (74.30%; p < 0.001) showed significant anti-fertility activity. No increase in activity was seen at higher doses. Meloxicam showed significant activity at doses of 3, 4, and 5 mg/kg. The combination of meloxicam (4 mg/kg) with ranitidine (70 mg) and famotidine (80 mg/kg) showed 100% anti-fertility activity. CONCLUSION: Our results indirectly confirm the combined involvement of histamine and prostaglandins in the implantation process. The mast cell stabilising property of H(2) blockers appears to be a possible mechanism for their anti-implantation activity.