BACKGROUND AND OBJECTIVE: In recent years, numerous attempts were done to find new treatment methods for patients with drug-resistant epilepsy. Anandamide (Anandamides; AEA) and di-Arachidonoylglycerol (2-Arachidonoylglycerol; 2-AG) are two major ligands of endocannabinoid system can be produced or deleted by a certain enzymatic pathway. Given the frequency and significance of these endocannabinoid ligands, it seems that endocannabinoid system in the brain can be changed with pharmacologically manipulating in the pathway of these two main ligands. Therefore, the aim of this study was to evaluate the effect of enzymatic elimination of endocannabinoids inhibitors on tonic-clonic seizure caused by PTZ.

METHODS: In this exprimental study 35 Adult male wistar rats were used in 4 groups. Tonic-colonic seizure was induced through single intra-peritoneal injection of PTZ (80 mg/Kg). Latency and duration of each five behavioral seizure stages were monitored for 30 minutes. To inhibit Anandamides elimination, URB and LY (URB: 1 mg/kg, LY: 2.5 mg/kg, i.p), to inhibit 2-2-Arachidonoylglycerol degradation WWL and JJKK (JJKK: 1 mg/kg, WWL: 5 mg/kg, i.p), were used, all dissolved in DMSO and injected 15 minutes before PTZ injection. In sham group, PTZ was injected after DMSO.Time and duration of all five behavioral stages of seizure were recorded for 30 minutes.

FINDINGS: Delay to stages 4 and 5 in DMSO+PTZ group were 206+39 and 209+39, respectivly. While in JJKK+WWL+DMSO+PTZ group delay to stages 4 and 5 were 630+159 and 726+360, respectivly, which reveald significant increase (p<0.05). In addition, percentage of stage 5 incidence and mortality rate were 91% in DMSO+PTZ group, while both indexes were decreased to 50% in (JJKK+WWL+DMSO) group.

CONCLUSION: Contemporary using both WWL and JJKK as inhibitors of 2-Arachidonoylglycerol elimination effectivly reduced tonic- clonic seizure.