Vigabatrin and tiagabine are pharmacologically different drugs. A pre-clinical study

In light of their closely related mechanisms of action, and preliminary cli nical evidence suggesting that they possess similar efficacies, it has been anecdotally suggested that vigabatrin and tiagabine may prove to be therap eutically indistinguishable. As a result, we have conducted a preclinical c omparison of their anticonvulsant profile and mechanism of action. Pentylen etetrazol and maximal electroshock seizures were employed to determine the experimental anticonvulsant profile. Mechanisms of action were investigated using assays of gamma-aminobutyric acid (GABA), GABA-transaminase and glut amic acid decarboxylase in mouse brain and GABA uptake and GABA-transaminas e in rat astrocyte cultures. Vigabatrin was without effect on either pentyl enetetrazol- or maximal electroshock-induced seizures, whereas tiagabine in creased the latency to pentylenetetrazol seizures and reduced the incidence of maximal electroshock seizures. In mouse brain assays, tiagabine was wit hout effect, while vigabatrin increased GABA concentrations and reduced GAB A-transaminase and glutamic acid decarboxylase activities. In cortical astr ocyte cultures, vigabatrin reduced the activities of both GABA uptake and G ABA-transaminase, whereas tiagabine blocked GABA uptake alone. These result s suggest that vigabatrin and tiagabine have differing efficacy in experime ntal seizure models and distinct neurochemical effects. It is possible, the n, that these drugs will have different spectra of activity and toxicity pr ofiles in human epilepsy. (C) 1999 BEA Trading Ltd.