Objectives: Thiamine serves as a cofactor for several enzymes involved in brain function and neurotransmitters biosynthesis. Thiamine-dependent enzymes are important for oxidant stress defenses. Several studies have reported that thiamine deficiency in the central nervous system reduces seizure threshold. The present study was designed to investigate the effect of acute and chronic administration of thiamine alone and in combination with sub-effective dose of diazepam on pentylenetetrazole (PTZ)-induced tonic-clonic seizures in mice.
Methods: Animals were randomly divided into control and experimental groups. In experimental groups, thiamine (50, 100, and 200 mg/kg i.p.) was administered acutely or chronically (once a day, for 14 days). Slow intravenous infusion of PTZ (5 mg/ml) by infusion pump with a constant rate (0.3 ml/min) was used to induce clonic and tonic seizures.
Results: Acute injection of thiamine (50, 100, and 200 mg/kg i.p.) did not increase seizure threshold significantly, but chronic treatment with thiamine (200 mg/kg i.p.) increases the clonic and tonic seizure threshold. Moreover, the combination of sub-effective dose of thiamine (100 mg/kg) and diazepam (0.1 mg/kg) significantly increased seizure threshold and enhanced the anticonvulsant effect of diazepam at ineffective dose (0.1 mg/kg).
Discussion: Our results suggest that thiamine can be considered as a potential add-on treatment in deficient and non-deficient thiamine epileptic patients. Co-administration of this vitamin with classic antiepileptics to decrease the required doses of regular drugs may be recommended. Nevertheless, more well-designed studies may be executed to provide further accurate information.
Keywords: Anticonvulsant; Mice; Pentylenetetrazole; Seizure; Thiamine.