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

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.