Phenolic anticyclooxygenase agents in antiinflammatory and analgesic therapy.

This report demonstrates that a non-steroidal antiinflammatory drug, MK 447, and phenol act similarly to inhibit cyclooxygenase activity in vitro in a dose-dependent manner when the concentration of peroxide activators is decreased by glutathione peroxidase. Increasing the rate of peroxide removal with higher amounts of glutathione peroxidase increases the inhibitory potency of the phenolic agents. The results support ascribing a vital role to tissue peroxides in facilitating prostaglandin biosynthesis in vivo. They also resolve the paradoxical problem of predicting antiinflammatory activity when an agent appears to stimulate prostaglandin formation. A corollary concept is that tissues with general hyperalgesic conditions may have lower levels of hydroperoxide than are found in inflammatory conditions, and thus be more amenable to therapy with phenolic agents like MK 447.