Detection of the role of voltage-gated sodium channels in the mechanism of anticonvulsant action of Gabapentin in chicks (in-vivo)

Abstract

Background:Because of the fact that the mechanism of anticonvulsant action of Gabapentin is not yet clear, so the aim of our present study was to determine whether the voltage-gated sodium channels (VGSC) may be correlate with its mechanism. To achieve this goal, Cypermethrin was chosen as a (convulsion inducer) resulting from its prolongs the opening of (VGSC) in order to interfere with Gabapentin . Method:The experiment animals were divided into four groups. The first group was treated with a single dose of Cypermethrin (1000 mg / kg, orally), while the second and third group were treated with a single dose of Gabapentin (100 mg / kg, orally)15 or 30 minutes before the Cypermethrin treatment respectively. The fourth group was treated with Gabapentin alone in a dose of (100 mg / kg, orally) .After the end of treatment of the chicks were transferred to the cages to be monitored individually and recorded percentages of appearance of nervous signs and the percentage of each mortality and protection against mortality. Results: Chicks treated with Cypermethrin alone (1000 mg / kg, orally)showed nervous signs which included the jerking movements of the leg and wings (clonic convulsion) and whole body tremors accompanied with opisthotonos at percentages (80%, 100%,60%) respectively that end with death at (100%) , but the pretreatment of chicks with Gabapentin (100 mg / kg, orally) resulted in time-dependent protection against Cypermethrin-induced nervous signs and mortality,which representing by significantly decrease in the percentage of each clonic convulsion,whole body tremors and mortality to (0%, 20% and 20%) respectively and accompanied by significant increase the percentage of protection of chicks against mortality to (80%) in the group that pretreatment with Gabapentin 30 minute before administration of Cypermethrin compared with control group (Cypermethrin alone). We conclude from our results that recorded for the first time the Gabapentin provided protection to chicks against Cypermethrin-induced nervous signs and mortality , this result may be related to effect of Gabapentin on (VGSC). Thus, the currently study will open the way to use Cypermethrin as a model in scientific research that detect the mechanisms of action of anticonvulsant drugs .