Abstract
"Non-antiepileptic" drugs have a strong potential as adjuvants in multidrug-resistant epilepsy treatment. In previous study the influence of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of classical commonly used anti-epileptic drugs under conditions of seizures, induced by pentylenetetrazole and maximal electroshock, has been investigated.
 The aim of the study was to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant potential of carbamazepine and lamotrigine in experimental seizures with different neurochemical mechanisms.
 Material and methods: A total of 192 random-bred male albino mice weighting 22–25 g were used. Carbamazepine and lamotrigine were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses: carbamazepine at doses of 100 and 50 mg/kg; lamotrigine at doses of 25 and 12.5 mg/kg. Digoxin was administered subcutaneously at a sub-cardiotonic dose of 0.8 mg/kg as an adjuvant to carbamazepine and lamotrigine in ½ ED50. Picrotoxin (2.5 mg/kg subcutaneously); thiosemicarbazide (25 mg/kg intraperitoneally); strychnine (1.2 mg/kg subcutaneously); camphor (1000 mg/kg intraperitoneally) were used as convulsant agents.
 Results: It was found that digoxin not only has its own permanent anticonvulsant effect on different models of paroxysms with different neurochemical mechanisms of development, but also significantly enhances the anticonvulsant potential of carbamazepine (to a lesser extent – lamotrigine) regardless of the pathogenesis of experimental paroxysms.
 Conclusion: Based on the results, it can be concluded that digoxin has a high potential as an adjuvant medicine in complex epilepsy treatment because it enhances the efficiency of low-dose traditional anticonvulsants carbamazepine and lamotrigine
Highlights
Despite a wide range of modern antiepileptic drugs (AEDs), most of which have multiple mechanisms of influence on the development of seizures [1, 2], every fourth patient with epilepsy is multidrug-resistant [3, 4]
The authors suggest that their anticonvulsant effect may be associated with blockade of transmembrane currents of sodium, potassium and calcium, or reduction of neuroinflammation, etc
We have previously investigated the effect of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of seven classical commonly used AEDs with different mechanisms of influence on the molecular mechanisms of epileptogenesis [12, 13]
Summary
Despite a wide range of modern antiepileptic drugs (AEDs), most of which have multiple mechanisms of influence on the development of seizures [1, 2], every fourth patient with epilepsy is multidrug-resistant [3, 4]. In parallel with the development of the latest AEDs, the search for promising correctors of refractory epilepsy among drugs of different pharmacological groups – the so-called “non-antiepileptic” drugs (nonAEDs) [5] Among such drugs, antiarrhythmic drugs deserve the highest attention – sodium, potassium and calcium channel blockers, as well as cyclooxygenase inhibitors, interleukin antagonists, angiotensin II receptor blockers, etc. The authors suggest that their anticonvulsant effect may be associated with blockade of transmembrane currents of sodium, potassium and calcium ( for antiarrhythmic drugs of I-IV classes according to the Vaughan-Williams classification), or reduction of neuroinflammation (for cyclooxygenase inhibitors, interleukin antagonists), etc It has been found, that the anticonvulsant activity of non-AEDs per se is moderate, but the addition of such drugs to traditional – classical – AEDs in various regimens for refractory epilepsy allows to achieve much more stable disease control [9]. Antiepileptic drugs have their own side effects (including AV blockade or sinus blockade for antiarrhythmic drugs, ulcerogenic effect for cyclooxygenase inhibitors, hypotension for angiotensin II receptor blockers), which justifies the advisability of further studies of their use in adjuvant therapy of epilepsy
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