Reuptake of GABA into the presynaptic neuron and glial cell
GABITRIL inhibits reuptake through highly selective binding to the GAT-1 transporter
GAT-1 is the predominant GABA transporter responsible for the reuptake of GABA into the presynaptic neurons and glial cells
GABA reuptake results in termination of postsynaptic neuronal action
GABITRIL Offers Targeted, GABA-Specific Action
Highly selective affinity for the GAT-1 transporter in vitro
Increases GABA levels in the synaptic cleft, thereby increasing postsynaptic neuronal action in preclinical models
The precise mechanism by which GABITRIL exerts its effect in humans is unknown
References:
1.
GABITRIL package insert, Cephalon, Inc.
2.
Fink-Jensen A, Suzdak PD, Swedberg MDB, Judge ME, Hansen L, Nielsen PG. The g-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats. Eur J Pharmacol. 1992;220:197-201.
3.
Giardina WJ. Anticonvulsant action of tiagabine, a new GABA-uptake inhibitor. J Epilepsy. 1994;7:161-166.
4.
Schachter SC. Tiagabine: current status and potential clinical applications. Exp Opin Invest Drugs. 1996;5:1377-1387.
5.
Borden LA, Murali Dhar TG, Smith KE, Weinshank RL, Branchek TA, Gluchowski C. Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur J Pharmacol. 1994;269:219-224.
