Temgicoluril exhibits anticonvulsant properties on experimental models of primary generalized epilepsy

Introduction. Epilepsy is one of the most common neurological diseases. The development of new, more potent and safe antiepileptic drugs remains an important task. Objective of the study. Evaluation of potential anticonvulsant effects of temgicoluril in average therapeutic doses in animal models of primary generalized epilepsy induced by corazol and maximum electric shock. Objective. Evaluation of potential anticonvulsant effects of temgicoluril at average therapeutic doses in animal models of primary generalized epilepsy induced by corazole and maximum electroshock. Materials and methods. Reproduced the corazolum (pentylenetetrazole) model in rats, and the maximum electric shock test (MES) in mice. For each experimental model of seizures, we subdivided the animals (42 mice and 42 rats) into 7 groups of 6 animals each. Group 1 was the control group; in groups 2, 3 and 4 animals were treated solely with temgicoluril at three doses of 10 mg/kg, 50 mg/kg and 100 mg/kg; in groups 5, 6 and 7 the animals were treated with reference antiepileptic drugs (bromdihydrochlorphenylbenzodiazepinum (2 mg/kg), valproic acid (400 mg/kg), and levetiracetam (54 mg/kg)). To the fnimals of control groups we administered equivalent amounts of distilled water. We administered all the studied drugs intraperitoneally within 30 minutes of the commencement of the experiment. To assess the reliability of the differences in samples having normal distribution, the parametric Student’s t-test was used. Results. In the corazole model in rats, intraperitoneal administration of temgicoluril at a dose of 10 mg/kg, 50 mg/kg and 100 mg/kg did not affect the number of seizures, but temgicoluril significantly reduced the duration of a seizure relative to the control (17±2.84): at a dose of 10 mg/kg by 5.6 times (3.2±0.1): at a dose of 50 mg/kg — by 6.2 times (2.7±0.4), and at a dose of 100 mg/kg by 8.9 times (1.9±0.2) (p ≤ 0.05). Temgicoluril at doses of 10 mg/kg and 50 mg/kg completely prevented death of rats in the corazole model of seizures. Animal mortality was observed only in the group that received temgicoluril at a dose of 100 mg/kg, which was 33.3 % (n = 2) and did not differ from the control group — 33.3 % (n = 2). In the maximum electric shock test on mice, temgicoluril at doses of 10, 50 and 100 mg/kg showed an anticonvulsant effect similar to the effect of reference drugs (bromdihydrochlorophenylbenzodi azepine, valproic acid and levetiracetam): temgicoluril completely stopped seizures caused by MES. Accordingly, such parameters as the latent period, the number of seizures, the duration of seizures and mortality were zero, in contrast to the control group. Conclusion. T emgicoluril in average therapeutic doses (10, 50 and 100 mg/kg) showed anticonvulsant activity in models of primary generalized epilepsy induced by corazole or maximum electric shock in animals (rats, mice).