Basic Mechanisms of Gabitril (Tiagabine) and Future Potential Developments


Address correspondence and reprint requests to Professor B. S. Meldrum at the Department of Clinical Neurosciences, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, U.K.


Summary: Gabitril (tiagabine) is a potent selective inhibitor of the principal neuronal γ-aminobutyric acid (GABA) transporter (GAT-1) in the cortex and hippocampus. By slowing the reuptake of synaptically-released GABA, it prolongs inhibitory postsynaptic potentials. In animal models of epilepsy, tiagabine is particularly effective against kindled (limbic) seizures and against reflexly-induced generalized convulsive seizures. These data are predictive of its efficacy in complex partial seizures in humans. Possible clinical applications outside the field of epilepsy include bipolar disorder and pain.