Epilepsy is recognized as one of the most common and serious
neurological disorder affecting 1-2% of the world׳s population. The present study demonstrates that systemic administration of 3-butyl-5,5-dimethyl-1,2,3-oxathiazolidine-4-one-2,2-dioxide (DIOXIDE), a synthetic compound bioisoster of
trimethadione and
phenytoin (classical
anticonvulsants), elicits a dose dependent
anticonvulsant response in mice submitted to the subcutaneous
pentylenetetrazole seizure test (scPTZ). Among various factors supposed to play role in
epilepsy, oxidative stress and reactive species have strongly emerged. The protection exerted by DIOXIDE over the extent of brain oxidative damage produced by PTZ was determined, by measuring the levels of lipid peroxidation and
reduced glutathione and the activity of Na(+)/K(+)-
ATPase.
Psychiatric disorders represent frequent comorbidities in persons with
epilepsy. In this report, the potential
anxiolytic and
antidepressant activities of DIOXIDE were evaluated in several widely used models for assessing
anxiolytic and
antidepressant activities in rodents. Although DIOXIDE did not evidence
anxiolytic activity at the doses tested, it revealed a significant
antidepressant-like effect. Preliminary studies of its mechanism of action, by means of its capacity to act via the GABAA receptor (using the [(3)H]
flunitrazepam binding assay in vitro and the
picrotoxin test in vivo) and the Na(+) channel (using the
alkaloid veratrine, a voltage-Na(+) channel agonist) demonstrated that the
anticonvulsant effect is not likely related to the GABAergic pathway and the
antidepressant-like effect could be due to its Na(+) channel blocking properties. The results for DIOXIDE suggested it as a new
anticonvulsant-
antioxidant and
antidepressant compound that deserves further development.