The anticonvulsant effect of the newly synthesized compounds was investigated by tests comprising pentylenetetrazole, thiosemicarbazide convulsions, and maximal electroshock (MES). Outbred mice (weight 18–22 g) were used for the study. In the case of convulsions induced by PTZ, it was injected subcutaneously at 90 mg/kg, which induced convulsions in 95% of animals (CD 95%). Each animal is placed into an individual plastic cage for observation lasting 1 h. Seizures and clonic convulsions were recorded. Substances were administered intraperitoneally (i.p.) at doses of 10–200 mg/kg in suspension with carboxymethylcellulose and Tween-80 45 min before administration of PTZ and applying electrical stimulation. The control animals were administered as an emulsifier. Every dose of each test compound was studied in six animals. The MES test is used as an animal model for the generalized tonic seizures of epilepsy. The parameters of MES were: 50 mA, duration of 0.2 s, and an oscillation frequency of 50 imp/s. The anticonvulsant properties of compounds were assessed by their prevention of the tonic-extensor phase of convulsions. Thiosemicarbazide, an antimetabolite of GABA inhibitor (glutamic acid decarboxylase) in the brain, is administered subcutaneously to mice at a dose of 18 mg/kg as a 0.5% solution, which causes clonic convulsions in animals. Anti-thiosemicarbazide activity was evaluated based on the latency time of the onset of seizures. Compounds were administered intraperitoneally at doses of 100 mg/kg in suspension with carboxymethylcellulose and Tween-80 45 min before administration of thiosemicarbazide. The comparative drug ethosuximide was administered in doses of 200 mg/kg and diazepam in doses of 2 mg/kg.
Sirakanyan S.N., Spinelli D., Petrou A., Geronikaki A., Kartsev V.G., Hakobyan E.K., Yegoryan H.A., Zuppiroli L., Zuppiroli R., Ayvazyan A.G., Paronikyan R.G., Arakelyan T.A, & Hovakimyan A.A. (2023). New Bicyclic Pyridine-Based Hybrids Linked to the 1,2,3-Triazole Unit: Synthesis via Click Reaction and Evaluation of Neurotropic Activity and Molecular Docking. Molecules, 28(3), 921.
Doses of the newly synthesized compounds (10-200 mg/kg, i.p.)
Dose of the comparative drug ethosuximide (200 mg/kg, i.p.)
Dose of the comparative drug diazepam (2 mg/kg, i.p.)
dependent variables
Incidence of convulsions induced by pentylenetetrazole (PTZ)
Incidence of tonic-extensor phase of convulsions in the maximal electroshock (MES) test
Latency time of the onset of seizures induced by thiosemicarbazide
control variables
Outbred mice with weight 18-22 g
Subcutaneous administration of PTZ at 90 mg/kg (CD 95%)
Subcutaneous administration of thiosemicarbazide at 18 mg/kg as a 0.5% solution
Electrical stimulation parameters for MES test (50 mA, 0.2 s, 50 imp/s)
Suspension vehicle (carboxymethylcellulose and Tween-80) for compound administration
Administration of the vehicle to control animals
controls
Positive control: Ethosuximide (200 mg/kg, i.p.)
Positive control: Diazepam (2 mg/kg, i.p.)
Negative control: Vehicle administration to control animals
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