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Considerable evidence has demonstrated the importance of PGE synthesis in the pathogenesis of periodontal disease. Although various cyclooxygenase inhibitors have been known to block periodontal PGE synthesis and prevent disease progression in animal models, there are few reports comparing relative efficacies of various inhibitors of arachidonic acid (ARA) metabolism. We have developed a sensitive in vitro assay to measure PGE synthesis in periodontal tissues. The apparent IC values (i.e. the concentration of drug which causes 50% inhibition of maximum PGE synthesis) have been determined for a series of arachidonic acid analogues as well as competitive and non-competitive cyclooxygenase inhibitors. Periodontal tissue homogenates were incubated in the presence ofH-arachidonic acid for 45 min at 37°C. Inhibitors were tested at 10-10 M and at zero concentration to measure conversion ofH-arachidonate toH-PGE. Log or half log dilutions of inhibitors were tested in triplicate for each assay. Radiolabeled PGE was extracted from homogenates, purified by reverse phase chromatography and quantitated by double antibody capture. RIA was performed on each homogenate to determine the amount of endogenous unlabeled PGE present in the sample to correct for antibody capture recovery. The apparent IC values were determined for each drug by averaging two or more replicate assays. Specific total enzymatic activity of periodontal tissue homogenates was typically 5-11 pg PGE/min/mg tissue. The following series of compounds were tested and are listed in order of increasing IC values: α-tocopherol (3.3×10 M), ketoprofen (5.4×10 M), indomethacin (1.0×10 M), flurbiprofen (1.5×10 M), meclofenamate (1.5×10 M), naproxen (2.5×10 M), docosahexaenoic acid (1.0×10 M), eicosapentaenoic acid (1.5×10 M), and ibuprofen (1.5×10 M). These data will enable the rational design of pharmacological formulations to inhibit periodontal tissue PGE synthesis and resultant inflammation, attachment loss and bone resorption. [ABSTRACT FROM AUTHOR]