Experimental model of convulsive syndrome based on phenylcarbamate

Introduction . Carbamates are widely used in the pharmaceutical industry, agriculture, and household chemicals. Being reversible cholinesterase inhibitors, carbamates can cause the development of generalized convulsive syndrome. Untimely treatment contributes to the emergence of persistent neurological disorders. In order to develop and adequately assess in preclinical studies the specific activity of new drugs for the relief of convulsive syndrome in acute intoxication with this group of substances, an easily reproducible experimental model of convulsive carbamate-induced syndrome is required. Objective . Development of an experimental model of generalized convulsive syndrome in rats using phenylcarbamate as a model toxicant for testing in preclinical studies of therapies for poisoning with cholinesterase inhibitors. Materials and methods. The study was performed using mongrel sexually mature male rats, aged 3 months (80 animals), divided into 4 groups (3 experimental and 1 control). At the first stage, the parameters of convulsive syndrome caused by model toxicants were compared: phenylcarbamate 1 mg/kg bw, corazol 65 mg/kg bw, and thiosemicarbazide 8 mg/kg bw. The following parameters were studied: motor activity (open field test), neuromotor functions (grip strength test), cognitive functions (conditioned avoidance responses, CAR), and cardiovascular indicators (ECG and cardiac rhythmogram assessment). The severity of the convulsive syndrome was identified by Racine stages. Additionally, the structure of brain tissues was evaluated by histological methods. second stage, biochemical parameters were studied in three experimental (with toxicants) and control groups. Some biochemical parameters were studied in the blood serum, assessing the function of the liver, kidneys, prooxidant and antioxidant systems. At the third stage, the activity of cholinesterase in the blood and brain was studied in 30 control and 30 experimental rats after phenylcarbamate exposure. Statistical processing of the results was carried out using Statistica v.10. Results . When modeling convulsive syndrome in rats, phenylcarbamate is comparable to corazol in terms of the onset of the latency period, duration and intensity of seizures. When implementing the model, a significant decrease in heart rate was recorded 48 h after administration. The CAR test found that the introduced substance increases the time of the first entry into the dark compartment before training. Significant changes in markers of liver function (ALT, bilirubin, cholesterol, triglycerides), lipid peroxidation and the antioxidant system (MDA, GPx) confirm the complexity of mechanisms responsible for the development of seizures and neurological disorders. The results of histological examination of brain tissues indicate that phenylcarbamate induces pronounced disorders of the brain structure in an experiment on rats. Conclusions . The developed experimental model of phenylcarbamate-based convulsive syndrome in rats is easy to reproduce, thus being recommended for preclinical studies of new drugs for the relief of convulsive syndrome in poisoning with cholinesterase inhibitors.