Tiagabine Pharmacology in Profile

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Abstract
Summary: Tiagabine (TGB) hydrochloride, a nipecotic acid derivative linked to a lipophilic anchor, potently and specifically inhibits uptake of the inhibitory neurotransmitter γ-aminobu-tyric acid (GABA) into astrocytes and neurons. With microdial-ysis, TGB has been shown to increase extracellular overflow of GABA in the midbrain of awake rats. TGB administration prolongs neuronal depolarization induced by iontophoretically applied GABA in hippocampal slices. TGB is effective in a wide range of seizure models, including pentylenetetrazol-induced, methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-car-boxylate (DMCM)-induced tonic, amygdala-kindled and picro-toxin-induced convulsions, and maximal electroshock seizures in rodents. In humans, TGB absorption is rapid and complete. It is metabolized in the liver, largely by isoform 3A of the cytochrome P450 family of enzymes. The process of elimination is linear, with a half-life of 5–8 h. TGB does not induce Or inhibit metabolic processes, although it provides a target for enzyme inducers that can lower its elimination half-life to 2–3 h. Accordingly, TGB does not alter the concentrations of other antiepileptic drugs (AEDs), with the possible exception of a small decrease in valproate levels. A controlled-release formulation of TGB would offset any potential clinical disadvantage of the short elimination half-life, particularly in patients receiving concurrent treatment with enzyme-induced AEDs.