Tiagabine (DB00906): A Comprehensive Pharmacological and Clinical Monograph

Section 1: Executive Summary & Drug Identification

1.1 Overview of Tiagabine: Key Characteristics and Clinical Role

Tiagabine is an anti-epileptic drug (AED) distinguished by its unique and highly specific mechanism of action: the selective inhibition of the gamma-aminobutyric acid (GABA) transporter 1 (GAT-1).[1] This mechanism enhances GABAergic neurotransmission, positioning Tiagabine as a targeted therapy for controlling neuronal hyperexcitability. Its primary, United States Food and Drug Administration (FDA)-approved clinical indication is as an adjunctive therapy for the treatment of partial-onset seizures in adults and adolescents aged 12 years and older.[3]

The clinical application of Tiagabine is fundamentally governed by a critical pharmacokinetic dichotomy: its metabolism is significantly influenced by the presence of hepatic enzyme-inducing concomitant medications. Patients co-administered enzyme-inducing AEDs (e.g., carbamazepine, phenytoin) exhibit markedly accelerated clearance of Tiagabine compared to "non-induced" patients. This metabolic variability necessitates distinct dosing and titration strategies for these two populations to ensure both efficacy and safety. While the drug has been explored for off-label uses, such as in anxiety disorders and neuropathic pain, its use in non-epileptic populations has been associated with significant safety concerns, including the paradoxical development of new-onset seizures, which has led to prominent regulatory warnings.[5] This report provides a comprehensive monograph on Tiagabine, detailing its chemical properties, pharmacological profile, clinical applications, safety considerations, and regulatory history.

1.2 Comprehensive Identification and Nomenclature