An excitatory amino acid reuptake inhibitor (EAARI) is a type of drug which inhibits the reuptake of the excitatory neurotransmitters glutamate and aspartate by blocking one or more of the excitatory amino acid transporters (EAATs).
Examples of EAARIs include dihydrokainic acid (DHK) and WAY-213,613, selective blockers of EAAT2 (GLT-1),[1][2] and L-trans-2,4-PDC, a non-selective blocker of all five EAATs.[3] Amphetamine is a selective noncompetitive reuptake inhibitor of presynaptic EAAT3 (via transporter endocytosis) in dopamine neurons.[4][5][6] L-Theanine is reported to competitively inhibit reuptake at EAAT1 (GLAST) and EAAT2 (GLT-1).[7]
Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons. ... internalization of EAAT3 triggered by amphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission.
In addition, RT-PCR and Western blot analysis revealed the expression of GLAST and GLT-1, astrocytic high-affinity glutamate transporters, in M5076 cells. Thus, theanine was shown to competitively inhibit the glutamate uptake by acting on these glutamate transporters.