Interaction of tiagabine with clonazepam in the mouse pentylenetetrazole-induced seizure model: a type I isobolographic analysis for parallel log-probit dose-response relationship lines
Journal Title: Journal of Pre-Clinical and Clinical Research - Year 2008, Vol 2, Issue 2
Abstract
Isobolographic analysis was used to characterize the interaction between tiagabine (TGB) and clonazepam (CZP) against pentylenetetrazole (PTZ)-induced clonic seizures in mice. The anticonvulsant effects of TGB in combination with CZP at 3 fi xed-ratios of 1:3, 1:1 and 3:1, were evaluated in the PTZ test in mice using type I isobolographic analysis for parallel dose-response relationship lines. Acute adverse-effect profiles for the combinations were determined by use of the step-through passive avoidance task (long-term memory), grip-strength (muscular strength), and chimney (motor coordination) tests. All combinations of TGB with CZP (at fixed-ratios 1:3, 1:1 and 3:1) were additive in terms of clonic seizure suppression in the PTZ test. Additionally, none of the examined combinations of TGB with CZP (at their median effective doses from the PTZ test) affected long-term memory, muscular strength and motor coordination in mice. Based on the isobolographic analysis of interaction, the combinations of TGB with CZP at the fixed-ratios 1:3, 1:1 and 3:1 displayed additivity in terms of suppression of PTZ-induced seizures and appear to be neutral combinations from a clinical viewpoint.
Authors and Affiliations
Jarogniew Łuszczki, Maciej Krzyżanowski, Marcin Sielski, Ewa Wojda, Mariusz Świąder
Keywords
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