The Mode of Action of Antithyroid Drugs: Results With Two in Vitro Tests

Abstract

1. Two in vitro tests are described for measuring the inhibitory potency of antithyroid drugs on enzymic and non-enzymic oxidative iodination of protein; one, a milk enzymic iodination test, and the other an enzyme-free peroxide iodination test.2. Five recognized antithyroid drugs have been tested : 2-thiouracil, 2-carbethoxythio-methylglyoxaline, potassium thiocyanate, resorcinol and sulphathiazole. By means of the milk enzymic test they could be ranged in order of potency, as indicated by the molar concentrations required for 50 % inhibition. They could also be separated into different types by the speed with which they pass from minimal to maximal inhibition with rising molar concentration.3. With the enzyme-free peroxide test, thiouracil, but not resorcinol, was found to be inert; with the enzymic test, both were nearly equivalent in potency.

Depression of Iodide Uptake of the Thyroid by Thiocyanate Through Blocking of the Energy Supply

“…Effect of NaSCN upon iodide metabolism of beef thyroid slices The results were presented in Table4 and Figure 2. At a concentration of 10-3M, NaSCN reduced the total uptake of I131, and the amount of inorganic Pitney and Fraser(1953)employing iodination test of milk-protein.…”

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“…The test procedure and the method of preparing the enzyme powder have been fully described by Pitney and Fraser (1953). The dry enzyme powder keeps satisfactorily in the refrigerator.…”

“…A preliminary report by Pitney and Fraser (1953) showed that the potency of antithyroid drugs may be assessed by two in vitro tests, and that such drugs may differ in their modes of action. In this communication we report further observations with these tests.…”

Section A. Physiology of dairy cattle: Hormones in reproduction and lactation

“…Lactation did not appear to be impaired by a 50% reduction in metabolic rate. Pitney & Fraser (1953) have investigated the mode of action of antithyroid drugs and conclude that thiouracil inhibits the iodinating enzymes, whereas another class of drug with antithyroid properties (e.g. resorcinol) removes iodine from combination with protein.…”