Theory of Reactions of Cells to Goitrogenic Thiopyrimidines

Abstract

An explanation of the action of the mercaptopyrimidines in the treatment of hyperthyroidism is proposed. It is suggested that thiouracil and thiothymine, in addition to reacting with iodine, act as antivitamins or antibiotics. The toxic reactions of these 2 compounds in vivo, especially the incidence of agranulocytosis and leukopenia, bear a marked resemblance in this regard to the toxic action of sulfanilamide, another antivitamin. In some individuals, these drugs interfere with the normal metabolism of certain body cells such as leukocytes, and even those present in the thyroid gland. A competition for thiouracil and thiothymine between iodine and other compounds which normally react with uracil and thymin may occur in vivo. This is confirmed by the fact that 6-ethyl-thiouracil and 6-normal propyl thiouracil are 8 and 11 times more effective, respectively, than equivalent amts. of thioura-cil, and exhibit no toxic reactions clinically. These 2 mercaptopyrimidines have had their structure altered to react wholly with 1, thus showing only a goitrogenic action. It might be predicted that thiocytosine, would not only exhibit antithyroid action, but might also be more toxic or show greater antivitamin action than either thiouracil or thiothymine, because structurally it is analogous to cytosine, a building block in not only 1 but 2 basic cell components, namely, thymus nucleic acid and ribonucleic acid. Uracil occurs only in ribonucleic acid, and thymine only in thymus nucleic acid.