Keywords
Abstract
The aim of this study – to investigate the influence of cardiac glycoside digoxin on the anticonvulsant activity of low-dose phenobarbital and clonazepam under models of primary generalized seizures with dif- ferent neurochemical mechanisms.
A total of 192 random-bred male albino mice have been used. Antiepileptic drugs (AEDs) were admin- istered 30 min before to seizure induction once intragastrically at conditionally effective (ED50) and sub- effective (1/2 ED50) doses: phenobarbital – at doses of 20 and 10 mg/kg; clonazepam – at doses of 0.1 and 0.05 mg/kg. Digoxin was administered once subcutaneously at subcardiotonic dose of 0.8 mg/kg body weight (1/10 LD50) 10–15 min before seizure induction. Picrotoxin (aqueous solution 2.5 mg/kg, subcutaneously), thiosemicarbazide (aqueous solution 25 mg/kg, intraperitoneally), strychnine (aqueous solution 1.2 mg/kg, subcutaneously), camphor (oil solution 1000 mg/kg, intraperitoneally) have been used as convulsive agents.
Digoxin has been shown not only to have a pronounced anticonvulsant effect under conditions of pri- mary generalized seizures induced by picrotoxin and strychnine, as well as moderate antagonism with thiosemicarbazide and camphor, but also significantly enhances the anticonvulsant potential of low doses
of classical drugs with well-known GABA-ergic properties – phenobarbital and clonazepam. Synergism with phenobarbital was particularly pronounced on the strychnine- and picrotoxin-induced models of sei- zures, to a lesser extent in the camphor-induced model, where the combination of an AED with a cardiac glycoside provided a complete protective effect – 100 % survival. In the model of thiosemicarbazide- induced seizures, the synergism of digoxin and phenobarbital was much weaker and related only to certain seizures’ indicators (statistically significant increase in the latency period of convulsions and decrease in the duration of the seizure period). Digoxin enhanced the anticonvulsant effect of a subeffective dose of clonazepam in the thiosemicarbazide- and strychnine-induced models, while cardiac glycoside did not interfere with the 100 % protective effect of clonazepam in the picrotoxin- and camphor-induced models of seizures.
The results obtained substantiate the expediency of further in-depth study of digoxin as an adjuvant drug in the treatment of epilepsy, in particular, its drug-resistant forms.