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Excitatory amino acid reuptake inhibitor

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]

See also


  1. ^ J. Storm-Mathisen; O.P. Ottersen (3 November 2000). Glutamate. Elsevier. p. 49. ISBN 978-0-08-053257-8.
  2. ^ Dunlop J, McIlvain HB, Carrick TA, et al. (October 2005). "Characterization of novel aryl-ether, biaryl, and fluorene aspartic acid and diaminopropionic acid analogs as potent inhibitors of the high-affinity glutamate transporter EAAT2". Mol. Pharmacol. 68 (4): 974–82. doi:10.1124/mol.105.012005. PMID 16014807.
  3. ^ Susan Napier; Matilda Bingham (5 May 2009). Transporters as Targets for Drugs. Springer Science & Business Media. p. 200. ISBN 978-3-540-87912-1.
  4. ^ "SLC1A1 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1 [ Homo sapiens (human) ]". NCBI Gene. National Center for Biotechnology Information. Retrieved 11 November 2014. 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.
  5. ^ Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG (July 2014). "Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons". Neuron. 83 (2): 404–16. doi:10.1016/j.neuron.2014.05.043. PMC 4159050. PMID 25033183.
  6. ^ Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA, Metzler V, Chaboz S, Ozmen L, Trube G, Pouzet B, Bettler B, Caron MG, Wettstein JG, Hoener MC (May 2011). "TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity". Proc. Natl. Acad. Sci. U.S.A. 108 (20): 8485–8490. doi:10.1073/pnas.1103029108. PMC 3101002. PMID 21525407.
  7. ^ Sugiyama T, Sadzuka Y, Tanaka K, Sonobe T (2001). "Inhibition of glutamate transporter by theanine enhances the therapeutic efficacy of doxorubicin". Toxicol. Lett. 121 (2): 89–96. doi:10.1016/s0378-4274(01)00317-4. PMID 11325559. 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.

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