Differential Effects of Meloxicam on Pentylenetetrazole- and Maximal Electroshock-Induced Convulsions in Mice

Abstract

Background: Epilepsy is a group of disorders associated with the abnormal electrical activity of different regions of the brain. The use of anticonvulsant drugs is limited because of their low efficacy, side effects, and toxicity. Therefore, research on new drugs for epilepsy is required. Meloxicam is a non-steroidal anti-inflammatory drug with several biological effects, such as antioxidant, neuroprotective, and anti-inflammatory. Objectives: Earlier studies gave conflicting reports on the effect of cyclooxygenase inhibitors on seizures. Accordingly, this study was designed to evaluate the effects of meloxicam on pentylenetetrazole (PTZ) and maximal electroshock (MES) models of convulsions Methods: For each model of convulsion, 48 mice were randomly divided into 6 groups of 8 animals. Group I in two models of convulsions were considered as the control group and the intraperitoneally (i.p.) received vehicle (10 mL/kg). Group II in the PTZ model received the reference anticonvulsant drug, diazepam (1 mg/kg, i.p.), and group II in the MES model was treated with phenytoin (25 mg/kg, i.p.). Groups III - VI in two models of convulsions received four different doses of meloxicam (2.5, 5, 10, and 20 mg/kg, i.p.), respectively. Thirty minutes later, convulsion was induced by PTZ (85 mg/kg, i.p.) in PTZ model and by using ear-clip electrodes in the MES model of convulsion. Results: In the PTZ model, meloxicam showed a significant delayed onset of seizures, Straub’s tail, and myoclonic seizure. Different doses of meloxicam reduced the mortality of animals in the PTZ model. In the MES model, meloxicam did not change the duration of hindlimb tonic extension and caused the death of animals unlike the PTZ model. Conclusions: According to the results, meloxicam has differential effects on two PTZ and MES models of seizure. The anticonvulsant and neuroprotective effects of meloxicam on the PTZ model may be mediated by anti-inflammatory and antioxidant properties. In the MES model, meloxicam did not show any beneficial effect and aggravated convulsive behavior. In the PTZ model, prostaglandins could be involved in the induction of convulsion. Conversely, in the MES model, prostaglandins may attenuate the severity of seizure at the basal level and prevent the development of convulsions. Nevertheless, more studies must be conducted to clarify the mechanisms of action of prostaglandins and meloxicam in the two PTZ and MES models of seizure.