COMPARATIVE STUDY OF THE ANTINOCICEPTIVE EFFECT OF ETIFOXINE AND RETIGABINE IN RATS

Abstract

Introduction: Etifoxine is a nonbenzodiazepine anxiolytic and anticonvulsant drug. It enhances GABAergic transmission directly by binding to β2 and/or β3 subunits of the GABAA receptor complex and indirectly via stimulation of neurosteroid production after the activation of 18 kDa translocator protein (TSPO). Retigabine is an anticonvulsant drug which activates low-threshold voltage-gated potassium channels. Anticonvulsant drugs reduce hyperexcitability and are currently extensively studied for possible antinociceptive activity. The aim of this study is to compare the antinociceptive effect of etifoxine and retigabine in rats. Materials and methods: The research included forty male Wistar rats, divided into five groups (n = 8). They were treated intraperitoneally with: 1st group (control) – saline 0,1ml/100g bw, 2nd group–metamizole natrii 150 mg/kg bw, 3rd group – etifoxine 50 mg/kg bw, 4th group –retigabine 5 mg/kg bw and 5th group – retigabine 15 mg/kg bw. The antinociceptive effect was evaluated with hot plate test and analgesy-meter test. The statistical analysis was performed using SPSS.17. Results: Etifoxine did not prolong the latency time in hot plate test and did not increase the withdrawal latency in analgesy-meter test, compared to the animals treated with saline. In hot plate test, retigabine in dose 15 mg/kg bw significantly increased the latency time at the second and third hour, compared to the control group (p<0.05). In analgesy-meter test, a significant increase of the withdrawal latency between retigabine and control animals occurred only at dose 15 mg/kg bw at first hour after single administration (p<0.05). Conclusions: The obtained experimental data show that etifoxine in dose 50 mg/kg bw does not have antinociceptive effect. Single administration of retigabine 15 mg/kg bw reduced painful thermal and mechanical stimuli in rats. The presence of KCNQ channels in the neuronal pathways of pain suggests that the antinociceptive effect of retigabine is maybe based on the activation of low-threshold potassium channels.