Vigabatrin and tiagabine are pharmacologically different drugs. A pre-clinical study.
In light of theirclosely related mechanisms of action, and preliminary clinical evidence suggesting that they possess similar efficacies, it has been anecdotally suggested that vigabatrin and tiagabine may prove to be therapeutically indistinguishable. As a result, we have conducted a preclinical comparison of their anticonvulsant profile and mechanism of action. Pentylenetetrazol 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 glutamic acid decarboxylase in mouse brain and GABA uptake and GABA-transaminase in rat astrocyte cultures. Vigabatrin was without effect on either pentylenetetrazol- or maximal electroshock-induced seizures, whereas tiagabine increased the latency to pentylenetetrazol seizures and reduced the incidence of maximal electroshock seizures. In mouse brain assays, tiagabine was without effect, while vigabatrin increased GABA concentrations and reduced GABA-transaminase and glutamic acid decarboxylase activities. In cortical astrocyte cultures, vigabatrin reduced the activities of both GABA uptake and GABA-transaminase, whereas tiagabine blocked GABA uptake alone. These results suggest that vigabatrin and tiagabine have differing efficacy in experimental seizure models and distinct neurochemical effects. It is possible, then, that these drugs will have different spectra of activity and toxicity profiles in human epilepsy.
Sills
G J
GJ
Epilepsy Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland, UK. g.j.sills@clinmed.gla.ac.uk
Butler
E
E
Thompson
G G
GG
Brodie
M J
MJ
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy*; D005069:Evaluation Studies as Topic; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009557:Nipecotic Acids / Q000627:therapeutic use*; D000078308:Tiagabine; D020888:Vigabatrin / Q000627:therapeutic use*
D000927:Anticonvulsants; D009557:Nipecotic Acids; D020888:Vigabatrin; D000078308:Tiagabine