At low concentrations, saccharin activates the human sweet taste receptor, but at high concentrations it inhibits sweetness by binding to allosteric sites.

Saccharin interacts with the human T1R2/T1R3 receptor in a unique dose-dependent manner. At concentrations below 3 mM, it binds to the orthosteric site on T1R2 to stimulate sweetness. However, above this threshold, saccharin also binds to allosteric inhibitory sites on both T1R2 and T1R3, suppressing the receptor’s response to other sweeteners. This complex interaction explains saccharin’s sweet taste at moderate levels and its bitter aftertaste or sweetness inhibition at higher doses.