The Anti-Convulsant Effects of Carvacrol in Penicillin- and Pentylenetetrazole-Induced Rat Models of Epilepsy

Abstract

Epileptic seizures are caused by abnormal neuronal excitation. It is well established that carvacrol, a monoterpenoid phenol, is able to inhibit the voltage-gated sodium channels and L-type Ca²⁺ channels and enhance activation of GABA(A) receptors. We therefore hypothesize that carvacrol may prevent epileptic seizures by inhibiting neuronal cation influx and facilitating anion influx. Herein, we investigated possible anti-convulsant effects of carvacrol on penicillin-induced epileptiform activity and pentylenetetrazole (PTZ)-induced seizures in rats. 63 male Wistar rats were assigned to the penicillin- and the pentylenetetrazole-induced groups. Both subgroups received three different doses of carvacrol (25, 75, and 150 mg/kg) intraperitoneally. Seizure stage, onset-times of both myoclonic-jerk and generalized tonic-clonic seizures and the duration of generalized tonic-clonic seizure were evaluated using Racine’s scale in PTZ group, while spike frequency and the amplitude of epileptiform discharges were evaluated in the penicillin-induced group. The administration of carvacrol significantly extended the onset time of the first myoclonic jerk (150 mg/kg, p = 0.019) and decreased the number of spike-waves (75 mg/kg, p = 0.033). This study showed that carvacrol has the anti-convulsant effect. However, this effect was observed at a low level. The limited the anti-convulsant effect of carvacrol may be due to its insufficient of acute effect related to the transition of carvacrol to the epileptic focus. More studies are needed to evaluate the effect of carvacrol on chronic epilepsy models and its molecular and pharmacokinetic mechanisms.