The anti-inflammatory activity of 1-methylimidazole-2-thiol (methimazole), the most widely used antithyroid drug, was investigated. Methimazole had a marked inhibitory action on prostaglandin H synthase (IC₅₀ = 10 µmol/l), inhibiting the peroxidase (IC₅₀ = 330 µmol/l), although the cyclo-oxygenase was slightly activated. Methimazole was less potent than indometacin (IC₅₀ = 1.7 µmol/l) on prostaglandin H synthase, but was more potent than acetylsalicylic acid (IC₅₀ =160 µmol/l). Methimazole has been found to trap superoxide (O^·₂) radicals and to decrease the level of blood prostaglandin E₂.

The effects of compounds with activity against thyroid peroxidase were tested on the activity of hydroperoxidase and cyclo-oxygenase of the prostaglandin synthetase complex in-vitro. Active compounds were found to inhibit the peroxidase, and the cyclo-oxygenase function. These compounds were also found to have anti-inflammatory activity as demonstrated by the reduction of carrageenan-induced oedema of the hind paw of the rat. Indomethacin and non-steroidal anti-inflammatory drugs tested under the same conditions were shown to have activity towards the cyclo-oxygenase rather than the peroxidase function of the prostaglandin synthetase complex. A common feature of the active compounds was the presence of an -NCS- linkage or free -SH group.