Basic mechanisms of gabitril (tiagabine) and future potential developments.
Gabitril (tiagabine) is a potent selective inhibitor of the principal neuronal gamma-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.
Meldrum
B S
BS
Department of Clinical Neurosciences, Institute of Psychiatry, Kings College, London, United Kingdom.
Chapman
A G
AG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy; D002352:Carrier Proteins / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018756:GABA Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology; D008032:Limbic System / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects; D026901:Membrane Transport Proteins; D051379:Mice; D009557:Nipecotic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D027361:Organic Anion Transporters; D010146:Pain / Q000188:drug therapy; D051381:Rats; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D002352:Carrier Proteins; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; C493413:SLC6A1 protein, human; C493414:Slc6a1 protein, mouse; C493415:Slc6a1 protein, rat; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine