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 PGF 2α to guinea pigs during the late stage of the estrous cycle, induced dose related uterine contractions and an elevation in uterine basal pressure similar 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) > indomethacin (0.65) > naproxen (0.52) > ibuprofen (0.43) > aspirin (0.31). The effectiveness of maximal response for suprofen was significantly greater than that of the other compounds tested. Simultaneous administration of suprofen with PGF 2α also blocked induction of uterine contractions, suggesting the possibility that suprofen also antagonizes PGF 2α receptor binding. Bradykinin also induced uterine constractions, an effect blocked by pretretment with suprofen. Finally, histochemical studies demonstrated stimulation of uterine catecholamine levels (norepinephrine) by arachidonic acid, PGF 2α 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 tretment of the uterine contractions associated with primary dysmenorrhea.
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