Sills, G. J., Butler, E., Thompson, G. G. and Brodie, M. J. (1999) Vigabatrin and tiagabine are pharmacologically different drugs. A pre-clinical study. Seizure, 8(7), pp. 404-411. (doi: 10.1053/seiz.1999.0326) (PMID:10600581)
Full text not currently available from Enlighten.
Abstract
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 γ -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.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Brodie, Professor Martin and Butler, Mrs Elaine and Sills, Dr Graeme |
Authors: | Sills, G. J., Butler, E., Thompson, G. G., and Brodie, M. J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Life Sciences College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
Journal Name: | Seizure |
Publisher: | Elsevier |
ISSN: | 1059-1311 |
ISSN (Online): | 1532-2688 |
University Staff: Request a correction | Enlighten Editors: Update this record