First Demonstration of a Functional Role for Central Nervous System Betaine/γ-Aminobutyric Acid Transporter (mGAT2) Based on Synergistic Anticonvulsant Action among Inhibitors of mGAT1 and mGAT2

  title={First Demonstration of a Functional Role for Central Nervous System Betaine/$\gamma$-Aminobutyric Acid Transporter (mGAT2) Based on Synergistic Anticonvulsant Action among Inhibitors of mGAT1 and mGAT2},
  author={H. Steve White and William Patrick Watson and Suzanne L. Hansen and Scott Slough and Jens Kristian Perregaard and Alan Sarup and Tina Bolvig and Gitte Petersen and Orla Miller Larsson and Rasmus Pr{\ae}torius Clausen and Bente Fr{\o}lund and Erik Falch and Povl Krogsgaard‐Larsen and Arne Schousboe},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={866 - 874}
In a recent study, EF1502 [N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-hydroxy-4-(methylamino)-4,5,6,7-tetrahydrobenzo [d]isoxazol-3-ol], which is an N-substituted analog of the GAT1-selective GABA uptake inhibitor exo-THPO (4-amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol), was found to inhibit GABA transport mediated by both GAT1 and GAT2 in human embryonic kidney (HEK) cells expressing the mouse GABA transporters GAT1 to 4 (mGAT1–4). In the present study, EF1502 was found to possess a broad… 

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