Subchronic Treatment with CBZ Transiently Attenuates Its Anticonvulsant Activity in the Maximal Electroshock-Induced Seizure Test in Mice.

Abstract

The objective of this study is to evaluate the anticonvulsant efficacy of carbamazepine (CBZ) following acute and chronic administration across four treatment protocols in a murine model of maximal electroshock-induced seizures. A single dose of the drug was utilized as a control. The neurotoxic effects were evaluated in the chimney test and the passive avoidance task. Furthermore, plasma and brain concentrations of CBZ were quantified across all treatment protocols. The subchronic administration of CBZ (7 × 2 protocol) resulted in an attenuation of its antielectroshock effect. In the three remaining treatment regimens (7 × 1, 14 × 1, and 14 × 2) the median effective doses of CBZ were comparable to the control. Neither acute nor chronic treatment with CBZ resulted in a discernible impact on motor coordination or long-term memory. The plasma and brain concentrations of CBZ were significantly lower in most chronic protocols when compared to a single-dose application. This may explain the transient attenuation of CBZ effectiveness in the 7 × 2 protocol, but not the return to the previous level. The anticonvulsant and neurotoxic profiles of CBZ did not differ after single and chronic administration. Therefore, experimental chronic studies with CBZ are not prerequisites for concluding and possibly translating results to clinical conditions.