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Glutamate transporter inhibitors and modulators act on the excitatory amino acid transporters (EAATs). Five subtypes, EAAT1 to EAAT5, use ion gradients to move glutamate from the synaptic cleft into astrocytes and neurons. Glutamate transporter 1 (GLT-1), the rodent form of EAAT2, accounts for most glutamate uptake in the forebrain. Mice lacking GLT-1 developed lethal spontaneous seizures and greater brain injury, which links this transporter to protection from excitotoxicity. DL-TBOA, described in 1998, blocks several EAAT subtypes without being transported. UCPH 101 selectively inhibits EAAT1, and WAY-213613 inhibits uptake through GLT-1/EAAT2. LDN-212320 raises GLT-1 expression, while GPNA hydrochloride inhibits the related alanine-serine-cysteine transporter 2 (ASCT2).
GPNA hydrochloride is a well known substrate of the enzyme γ-glutamyltransferase (GGT). GPNA hydrochloride is a specific glutamine (Gln) transporter ASCT2 inhibitor.
