DL-TBOA ammonium is a potent, non-transportable inhibitor of excitatory amino acid transporters. Its inhibitory effects are demonstrated by IC50 values of 70 μM, 6 μM, and 6 μM for excitatory amino acid transporter-1 (EAAT1), EAAT2, and EAAT3, respectively. Additionally, DL-TBOA ammonium significantly hampers the uptake of [14C]glutamate in COS-1 cell lines expressing human EAAT1 and EAAT2, evident by Ki values of 42 μM and 5.7 μM, respectively. Furthermore, this compound competitively blocks EAAT4 and EAAT5, with Ki values of 4.4 μM and 3.2 μM, respectively.

EAAT2:6 μM (IC50), EAAT3:6 μM (IC50), EAAT2 (human):5.7 μM (IC50), EAAT1 (human):Ki: 42 μM, EAAT4:4.4 μM (IC50), EAAT1:70 μM (IC50), EAAT5:3.2 μM (IC50)

DL-TBOA ammonium treatment at concentrations ranging from 70 to 350 μM over 48 hours was observed to concentration-dependently enhance the reduction in cell viability caused by SN38 and also reversed the reduction in cell viability induced by Oxaliplatin in both HCT116 and LoVo cell lines. Additionally, DL-TBOA ammonium at a concentration of 350 μM applied for 24 hours led to decreased p53 induction by both SN38 and oxaliplatin in the same cell lines. These outcomes, derived from cell viability assays, underscore DL-TBOA ammonium’s potential modulatory effects on chemotherapeutic-induced cell death and p53 induction.

Administering DL-TBOA ammonium (10 nmol; intracerebroventricularly, i.c.v.) to male Sprague-Dawley rats (180-250 g) dependent on morphine markedly enhances both the manifestation of somatic symptoms precipitated by naloxone (0.1 mg/kg) and the development of conditioned place aversion. This effect was observed in a dose-dependent manner with dosages of 1 nmol, 3 nmol, and 10 nmol, demonstrating increased severity of symptoms related to naloxone-induced morphine withdrawal.