Na+-K+-2Cl^– Cotransport Inhibitors and their Effect on Induced Seizure Tests in Experimental Models

Objective: To evaluate the antiseizure activities of Na+-K+-2Cl– cotransport inhibitors in chemically and electrically induced seizure test models in Wistar albino rats.

Methods: The study protocol was approved from the Institutional Animal Ethics Committee (IAEC). All animal ethics guidelines (CPCSEA and INSA) were followed throughout the study period. In this study, two screening test models were used one with chemically induced (pTZ) and another with the electrically induced (MES) on healthy, adult Wistar albino rats. The groups of study included, group I: control for PTZ, group II: standard for PTZ (Sodium valproate, i.p.), group III: furosemide for PTZ (i.p.), group IV: torsemide for PTZ (i.p.), group V: control for MES, group VI: standard for MES (diphenylhydantoin, i.p.), group VII: furosemide for MES (i.p.), and group VIII: torasemide for MES (i.p.). One-way ANOVA followed by Bonferroni's post hoc test was used for analysis of data. p-Value of less than 0.05 was considered as statistically significant.

Results: This study found that there was a reduction in total duration of seizures in seconds in both the experimental test drug groups (furosemide and torasemide), that is, groups III and IV, respectively, in comparison to the control group I with p < 0.05. It was also found that there was decline in scores of seizures and total number of seizures in one hour in both the experiential test drug groups III and IV when compared with the group I (p < 0.01). The statistically significant difference was also noted with the onset of seizure parameter among group I (control for PTZ) in comparison with groups III and IV (p < 0.001). All the above parameters were comparable to the standard group II in respect to the groups III and IV with p-value more than 0.05. In MES model, the parameters like (scores and THLE [tonic hind limb extension]) were also statistically significant different among groups VII and VIII when compared with the control group (group V) for MES with p-value less than 0.05. The above two parameters were also comparable to the standard drug group (group VI) for MES model in respect to the experimental test drug groups (group VII and VIII) with p-value more than 0.05.

Conclusion: Na+-K+-2Cl^– cotransport inhibitors (furosemide and torasemide) exhibited significant antiseizure activities in chemically (pTZ) and electrically (MES) induced seizure model tests in Wistar albino rats.