Thyroid peroxidase inhibitors

Thiourea derivatives are known for their anti-thyroid effects due to inhibition of thyroid peroxidase [1], Two thiourea compounds especially, have found wide application in the treatment of patients with hyperthyroidism, i.e., PTU and 2-mer-capto-l-methylimidazole (methimazole). It was soon recognized, however, that while methimazole only blocks thyroid hormone synthesis PTU has an additional effect on thyroid hormone metabolism [13]. These clinical findings have been confirmed in vitro showing that PTU, but not methimazole, is a potent inhibitor of the type I deiodinase [5-8]. Structure-activity studies of thiourea analogues [44,45] have... 

Some bioactive flavones include aldose reductase inhibitors (apigenin 4 -methyl ether (acacetin), apigenin 7-0-apioside (apiin), 5,7-dihydroxyflavone (chrysin) and luteolin) antiinflammatory 5-LOX inhibitors (5,6,7-trihydroxyflavone (baicalein), 5,6,3, 4 -tetrahydroxy 7-methoxyflavone (pedalitin), 5,3, 4 -trihydroxy 6,7-dimethoxyflavone (cirsiliol, 6-0-methylpedalitin) and flavone) a COX inhibitor (flavone) iodothyronine deiodinase inhibitors (acacetin, chrysin and luteolin) a NADH and succinate dehydrogenase inhibitor (luteolin) millet-derived, goitrogenic inhibitors of thyroid peroxidase (flavone C-glycosides orientin and vitexin) and protein kinase inhibitors (acacetin, apigenin, baicalein, flavone, luteolin, 5,7,3, 4, 5 -pentahydroxyflavone (tricetin) and tricetin 3, 4, 5 -trimethyl ether). 

The patient usually starts with 20 mg of thiamazole (methimazole), unless iodine-induced or severe hyperthyroidism exists, necessitating a higher starting dose (Table 81.2). Doses of thionamide drugs are lower in the case of iodine deficiency because the drugs act as competitive inhibitors of thyroid peroxidase and are antagonized by iodine. The doses have to be adjusted individually and, after restoration of euthyroidism, should be reduced to a lower maintenance dose (2.5—10 mg of thiamazole). 

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