680C91 is a potent and selective inhibitor of TDO, and its Ki is 51 nM.

68OC91, a potent (Ki = 51 nM) and selective TDO inhibitor, has no inhibitory activity against monoamine oxidase A and B, indoleamine 2,3-dioxygenase (EC 1.13.11.17), 5-HT uptake and 5-HT1A,5-HT1D,5-HT2A and 5-HT2c receptors at a concentration of 10 μM. 68OC91 has no effect on the binding of tryptophan to albumin in plasma and inhibited TDO competitively with respect to its substrate tryptophan. 68OC91 inhibits the catabolism of tryptophan by rat liver cells and rat liver perfused in situ.[1]

Prior administration of 68OC91 inhibits the catabolism of L-[ring-2-14C]-tryptophan and a load dose of tryptophan (100 mg/kg) in vivo. Administration of 68OC91 alone significantly increases brain tryptophan, 5-HIAA and 5-HT. A load dose of tryptophan (100 mg/kg), producing increases in brain tryptophan 4-fold greater than that seen with 68OC91, does not increase brain 5-HIAA and 5-HT to levels greater than those seen with 68OC91 and produces a shorter-lasting increase in these parameters.[1]

Cell lines: rat liver cells. Concentrations: 0.1 μM, 0.5 μM, 2 μM. Incubation Time: 0 min - 120 min. Method: The combined concentration of non-labelled L-tryptophan and the L-[ring-2-14C]-tryptophan used in the assays is 20 μM and is added either with or without 68OC91 at time zero.

Animal Models: Male Wistar rats. Dosages: 15 mg/kg. Administration: Oral gavage