inhibitor of excitatory amino acid transporters
CAS：205309-81-5
分子式：C11H13NO5
分子量：239.23
纯度：98%
存储：Store at -20°C

Background:

Ki: 42 μM for EAAT1; 5.7 μM for EAAT2

Glutamate acts as an excitatory neurotransmitter in the mammalian central nervous system and a potent neurotoxin. Glutamate transporters also play an important role in maintaining the extracellular glutamate concentration below neurotoxic levels and therefore contribute to the prevention of neuronal damage. DL-TBOA was synthesized and examined as an inhibitor of sodium-dependent glutamate/aspartate transporters(excitatory amino acid transporters).

In vitro: DL-TBOA inhibited the uptake of [14C]glutamate in COS-1 cells overexpressing the human excitatory amino acid transporter-1 (EAAT1) (Ki = 42 μM) with almost the same potency as DL-threo-b-hydroxyaspartate (Ki = 58 μM). With regard to the human excitatory amino acid transporter-2 (EAAT2), the inhibitory effect of DL-TBOA (Ki = 5.7 μM) was much more potent than that of dihydrokainate (Ki = 79 μM), which is well known as a selective blocker of this subtype. [1].

In vivo: Microdialysis administration of 500 μM DL-TBOA into the hippocampus increased 3.4- and nine-fold the extracellular levels of aspartate and glutamate, respectively. Upon stereotaxic administration it induced neuronal damage dose-dependently in CA1 and dentate gyrus, and convulsive behavior. Electroencephalographic recording showed limbic seizures appearance in the hippocampus after DL-TBOA infusion. [2].

Clinical trial: Up to now, DL-TBOA is still in the preclinical development stage.

Reference:
[1] Shimamoto K, Lebrun B, Yasuda-Kamatani Y, Sakaitani M, Shigeri Y, Yumoto N, Nakajima T.  DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Mol Pharmacol. 1998 Feb;53(2):195-201.
[2] Montiel T, Camacho A, Estrada-Sánchez AM, Massieu L.  Differential effects of the substrate inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (PDC) and the non-substrate inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo. Neuroscience. 2005;133(3):667-78.