The results of preclinical investigations suggest that vigabatrin and tiagabine are pharmacologically distinct compounds with different anticonvulsant, neurotoxicity, and pharmacokinetic profiles (Sills 2003). It is possible that they will ultimately prove to have different clinical efficacies and spectra of activity. The molecular formula of tiagabine is C20 H25 NO2 S2 HCl.
Pharmacodynamics. The precise mechanism of the antiseizure effect of tiagabine is unknown, although it is believed to be related to its ability to enhance the activity of GABA, the major inhibitory neurotransmitter in the CNS. Tiagabine binds to recognition sites associated with the GABA uptake carrier and blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of postsynaptic cells. Inhibition of GABA uptake has been shown for synaptosomes, neuronal cell cultures, and glial cell cultures. Tiagabine increases the amount of GABA available in the extracellular space of the globus pallidus and substantia nigra.
A neuroimaging study using 18F fluorodeoxyglucose-PET has shown that following tiagabine treatment, regional cerebral metabolic rate of glucose uptake in ventral medial prefrontal cortex increased significantly in patients with generalized social anxiety disorder (Evans et al 2009). These findings suggest that therapeutic effects of tiagabine in this disorder may be mediated via GABAergic modulation of ventral medial prefrontal cortex.
Pharmacokinetics. Features of pharmacokinetics of tiagabine are:
The pharmacokinetics of total and unbound tiagabine are unaffected in subjects with renal failure requiring hemodialysis.