Anticonvulsant activity of a newly synthesized analgesic from the hexaazaisowurtzitanes class. (Experimental study)

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Abstract
Objective. To study anticonvulsant activity of thiowurtzine in seizure models induced by pentylenetetrazol and thiosemicarbazide. Material and methods. Experiments were conducted on male CD-1 mice. Thiowurtzine was administered intragastrically at doses of 50, 100 and 200 mg/kg. Carbamazepine (100 mg/kg) was used as a reference drug. Anticonvulsant activity was investigated in antagonism tests with pentylenetetrazol (PTZ 140 mg/kg subcutaneously) and thiosemicarbazide (TSC 30 mg/kg subcutaneously). Anticonvulsant activity was assessed considering latency of various seizure stages, their frequency, and animal survival. Results. In PTZ test, thiowurtzine 100 mg/kg significantly prolonged latent period of myoclonic seizures by 92% and clonic seizures by 95%, as well as survival time by 73% compared to the control group. All changes were significant. Survival reached 41.7% that was comparable to the effect of carbamazepine. At 200 mg/kg, efficacy decreased that indicated a narrow therapeutic window. In TSC model, thiowurtzine did not significantly affect survival. However, dose 100 mg/kg reduced the number of the most severe tonic seizures by 31%. Conclusion. Thiowurtzine possesses anticonvulsant activity, most pronounced in GABA-dependent pentylenetetrazol model. These data indicate membrane-stabilizing effect and expand potentials for this compound in comorbid conditions.

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