Hahn D W, Carraher R, McGuire J L
Prostaglandins. 1982 Jan;23(1):1-16. doi: 10.1016/0090-6980(82)90017-x.
An in situ model for studying factors related to dysmenorrhea and for evaluating drugs for their inhibitory effects on uterine contractility induced by arachidonic acid and prostaglandins has been developed. Intravenous administration of arachidonic acid and PGF2 alpha to guinea pigs during the late stage of the estrous cycle, induced dose related uterine contractions and an elevation in uterine basal pressure similar to that seen in patients with dysmenorrhea. Pretreatment with prostaglandin synthetase inhibitors inhibited the response to arachidonic acid. The order of relative potency was suprofen (1) greater than indomethacin (0.65) greater than naproxen (0.52) greater than ibuprofen (0.43) greater than aspirin (0.31). The effectiveness or maximal response for suprofen was significantly greater than that of the other compounds tested. Simultaneous administration of suprofen with PGF2 alpha also blocked induction of uterine contractions, suggesting the possibility that suprofen also antagonizes PGF2 alpha receptor binding. Bradykinin also induced uterine contractions, an effect blocked by pretreatment with suprofen. Finally, histochemical studies demonstrated stimulation of uterine catecholamine levels (norepinephrine) by arachidonic acid, PGF2 alpha and bradykinin. These effects were blocked by suprofen. These data suggest that suprofen, an analgesic prostaglandin synthetase inhibitor, may be of use in the clinical treatment of uterine contractions associated with primary dysmenorrhea.
已建立一种原位模型，用于研究与痛经相关的因素，并评估药物对花生四烯酸和前列腺素诱导的子宫收缩的抑制作用。在动情周期后期，对豚鼠静脉注射花生四烯酸和前列腺素F2α，可诱导出与剂量相关的子宫收缩，并使子宫基础压力升高，类似于痛经患者所见情况。用前列腺素合成酶抑制剂预处理可抑制对花生四烯酸的反应。相对效力顺序为：舒洛芬（1）大于吲哚美辛（0.65）大于萘普生（0.52）大于布洛芬（0.43）大于阿司匹林（0.31）。舒洛芬的有效性或最大反应明显大于所测试的其他化合物。舒洛芬与前列腺素F2α同时给药也可阻断子宫收缩的诱导，提示舒洛芬也可能拮抗前列腺素F2α受体结合。缓激肽也可诱导子宫收缩，该作用可被舒洛芬预处理阻断。最后，组织化学研究表明，花生四烯酸、前列腺素F2α和缓激肽可刺激子宫儿茶酚胺水平（去甲肾上腺素）。这些作用被舒洛芬阻断。这些数据表明，舒洛芬作为一种止痛性前列腺素合成酶抑制剂，可能可用于临床治疗与原发性痛经相关的子宫收缩。
