Experimental assessment of 2-oxyindolin-3-glyoxylic acid derivative anticonvulsant effect

Abstract

Aim. To explore the anticonvulsant effect of 2-oxyindolin-3-glyoxylic acid derivative on the model of acute myoclonic seizures caused by pentylenetetrazol, picrotoxin and thiosemicarbazide.Methods. Median effective dose (ED50) of 2-hydro-N-naphthalene-1-yl-2-(2-oxy-1,2-dyhydro-indole-3-ylidene)-acetamide diethyl ether was determined by the maximal electroshock test in experiments on adult Wistar rats of both gender. The effect of median effective dose prophylactic administration of the study medication and comparators - diazepam and sodium valproate - on chemo-induced epileptogenesis was explored. Introduction of proconvulsant drugs (pentylenetetrazol, picrotoxin and thiosemicarbazide) was accompanied by the development of seizures, which was estimated by the intensity of seizures (points), latent period of seizures onset (seconds), the number of convulsive attacks, seizures, duration (seconds) and the number of survived animals in each group.Results. Median effective dose of 2-oxyindolin derivative was 12 mg/kg as measured by maximal electroshock test. This dose of the test compound, similar to diazepam, effectively reduced the severity of seizures caused by pentylenetetrazol, seen as the increased duration of latent period before the seizures onset by 1.9 times, decreased severity of seizures by 1.7 times, decreased number of seizures by 2.1 times, and decreased seizure duration by 2.3 times together with lower mortality. The prophylactic administration of the substance has extended the latent period of seizures by 2.0 times, significantly reduced the number, intensity and duration of seizures, decreased the mortality after administration of picrotoxin. Also, 2-oxyindolin derivative significantly increased the latent period of seizures onset and reduced the severity of seizures due to thiosemicarbazide. At that, the study substance was not inferior in anticonvulsant activity compared to the diazepam as the reference drug.Conclusion. The dose of 12 mg/kg of 2-hydro-N-naphthalene-1-yl-2-(2-oxy-1,2-dyhydro-indole-3-ylidene)-acetamide was effective in preventing seizures associated with gamma-aminobutyric acid (GABA)-convulsants.