Additive Interactions between 1-Methyl-1,2,3,4-Tetrahydroisoquinoline and Clobazam in the Mouse Maximal Electroshock-Induced Tonic Seizure Model - An Isobolographic Analysis for Parallel Dose-Response Relationship Curves

Abstract

Background: The aim of this study was to characterize the anticonvulsant effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ) in combination with clobazam (CLB) in the mouse maximal electroshock-induced seizure (MES) model. Methods: The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the mouse MES model was determined using an isobolographic analysisfor parallel dose-response relationship curves. Results: Electroconvulsions were produced in albino Swiss mice by a current (sine wave, 25 mA, 500 V, 50 Hz, 0.2-second stimulus duration) delivered via auricular electrodes by a Hugo Sachs generator. There was an additive effect of the combination of 1-MeTHIQ with CLB (at the fixed ratios of 1:3, 1:1 and 3:1) in the mouse MES-induced tonic seizure model. Conclusions: The additive interaction of the combination of 1-MeTHIQ with CLB (at fixed-ratios of 1:3, 1:1 and 3:1) in the mouse MES model seems to be pharmacodynamic in nature and worth of considering in further clinical practice.

Polygonogram and isobolographic analysis of interactions between various novel antiepileptic drugs in the 6-Hz corneal stimulation-induced seizure model in mice

“…It should be stressed that in the 6 Hz corneal stimulation-induced seizure model we used a current intensity of 32 mA, which was associated with full efficacy of LEV and other tested antiepileptic drugs in suppression of limbic (psychomotor) seizures in mice. Since all of the tested antiepileptic drugs produced the definite antiseizure effects in the 6-Hz corneal stimulation-induced seizure model, it was possible to correctly classify interactions between the second-generation antiepileptic drugs by means of the type I isobolographic analysis of interaction, as recommended elsewhere [22,[51][52][53][88][89][90].…”

A Long-Term Treatment with Arachidonyl-2′-Chloroethylamide Combined with Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy

“…Until recently, epilepsy treatment was mainly aimed at stopping seizures. However, for the past several years many researchers have focused their efforts on searching for new, potent anticonvulsant, natural or synthetic, which will not only stop seizures, but also have neuroprotective properties and no side effects [1,2,3,4,5]. Because human TLE is the most common type of epilepsy, animal models of these conditions are thought to be best in helping us understand the problem of epileptogenesis and the neuronal alterations taking place in a given region of the brain after convulsions [6].…”

Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis

“…In preclinical studies, the nature of interactions between antiepileptic drugs is usually characterized using the isobolographic analysis [9,10] . This is the reason to investigate the interactions between retigabine and levetiracetam in the mouse MES model with isobolographic analysis.…”