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.

Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

“…2021, 89, 22 2 of 10 represent a powerful tool for modern anticonvulsant design [15,16]. A number of approved NSAIDs from many chemical chemotypes were evaluated in various screening convulsive models and were found to be effective, as well as prospects for subsequent experiments (Figure 1) [17][18][19][20][21][22].…”

“…, 89, 22 2 of 10 regulation [11], free radical formation [12], and cyclooxygenases-1 and 2 (COX-1/2) upregulation, etc. [13,14].…”

“…Therefore, potential NSAIDs with different mechanisms of action represent a powerful tool for modern anticonvulsant design [15,16]. A number of approved NSAIDs from many chemical chemotypes were evaluated in various screening convulsive models and were found to be effective, as well as prospects for subsequent experiments (Figure 1) [17][18][19][20][21][22]. Both primary enzymes COX-1 and COX-2, which catalyze the synthesis of inflammatory prostanoids and are main targets for NSAIDs, have been reported as potential neurotherapeutic targets for epilepsy correction and management [14,16,23].…”

Identification of New Carbonic Anhydrase VII Inhibitors by Structure-Based Virtual Screening

“…In the MES model, none of them were active when administered alone; in fact, meloxicam caused an increase in the mortality rate of treated animals. 50,51 Piroxicam, in contrast, increased the protection of valproate and phenytoin. 50 In the PTZ model, meloxicam demonstrated anticonvulsant and neuroprotective effects at 10 mg/kg in mice.…”

Meloxicam, a selective COX-2 inhibitor, displays anticonvulsive effects in pentylenetetrazole-induced acute seizures in mice through GABA and glutamate mediated mechanism

“…Meloxicam inhibits prostaglandin biosynthesis in inflammation through COX-2 inhibiting effect [12]. In previous studies, meloxicam was observed to increase the first myoclonic jerk (FMJ) time in acute pentylenetetrazole (PTZ) epilepsy model [13] and to reduce the levels of myeloperoxidase and malondialdehyde and to reintegrate the brain glutathione content [14]. Finally, in a study of kindling model epilepsy in mice, meloxicam reduced inflammation and oxidative stress, and thus it showed antiepileptic effects [15].…”