Anti-inflammatory action of methimazole.

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 mumol/l), inhibiting the peroxidase (IC50 = 330 mumol/l), although the cyclo-oxygenase was slightly activated. Methimazole was less potent than indometacin (IC50 = 1.7 mumol/l) on prostaglandin H synthase, but was more potent than acetylsalicylic acid (IC50 = 160 mumol/l). Methimazole has been found to trap superoxide (O2.-) radicals and to decrease the level of blood prostaglandin E2.

Biological evaluation of compounds with -NCS- group or derived from thiazole and imidazole. Activity on prostaglandin synthetase complex.

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.

[Antibacterial sulfonamides, antiparasitic and antifungal derivatives of imidazole: evaluation of their antithyroid effects in the rat]. / Sulfamides antibactériens, antiparasitaires et antifongiques dérivés de l'imidazole: évaluation des effets antithyroïdiens sur le rat.

Antithyroid action of some antibacterial, antiparasitic or antifungal agents, was studied by 2 in vitro and 3 in vivo experimentations in the rat. These drugs can upset thyroid hormone synthesis by forming a molecular complex with iodine, and/or by inhibiting thyroid peroxidase activity. Rats treated with these drugs showed an hypothyroidism, demonstrated both by a decrease in T4 concentration and an hyperactivity of thyroid gland by positive feed-back, whose consequence was the presence of cylindrical cells. We noticed this iatrogenic hypothyroidism with all the drugs experimented, by an increase in thyroid gland weight. But the increase of rats body weight, which should have appeared, was not shown. The use of anabolic steroid is now forbidden, therefore, such drugs could be used for breeding animals, in order to gain body weight. Detection of use of these drugs in breeding, to obtain this side effect, should be advised.

Synthesis and inhibitory effects of 1,2,4-triazole derivatives on platelet aggregation.

Various derivatives of triazole substituted in the 2-position were prepared, and their activity on platelet aggregation tested. Compounds 4 and 14 had the most powerful action. These agents were thought to inhibit platelet aggregation via an inhibition of the cyclo-oxygenase-peroxidase complex (PGS complex), preventing synthesis of prostaglandins.