Agrawal S S, Alvin Jose M
*Anti-fertility and Infertility Research Centre, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), New Delhi.
Eur J Contracept Reprod Health Care. 2009 Dec;14(6):444-50. doi: 10.3109/13625180903258695.
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.
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.
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.
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.
鉴于组胺和前列腺素在着床过程中的作用，评估H₂受体阻滞剂雷尼替丁和法莫替丁以及环氧化酶抑制剂美洛昔康单独及联合使用时的抗着床活性。
在通过观察阴道涂片确认交配后，立即对雌性白化Wistar大鼠口服不同剂量水平的药物，持续1至7天。在妊娠第10天进行剖腹手术，计算着床数和黄体数，并测定着床前后的损失。使用体外和体内方法研究肥大细胞稳定活性。
雷尼替丁70 mg/kg（75.41%；p < 0.01）和法莫替丁80 mg/kg（74.30%；p < 0.001）显示出显著的抗生育活性。更高剂量时活性未见增加。美洛昔康在3、4和5 mg/kg剂量时显示出显著活性。美洛昔康（4 mg/kg）与雷尼替丁（70 mg）和法莫替丁（80 mg/kg）联合使用显示出100%的抗生育活性。
我们的结果间接证实了组胺和前列腺素在着床过程中的联合作用。H₂受体阻滞剂的肥大细胞稳定特性似乎是其抗着床活性的一种可能机制。
