Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action—A Critical Review of Experimental Findings

Borowicz-Reutt, Kinga K.

doi:10.3390/ijms23052891

Cited by 6 publications

(3 citation statements)

References 77 publications

(130 reference statements)

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“…In our previous work, we thoroughly studied the interactions between antiepileptic and antiarrhythmic drugs of all classes in the maximal electroshock test in mice, the commonly accepted animal model for studying tonic-clonic convulsions [ 14 ]. The involvement of oxidative stress in both cardiovascular disorders and epilepsy [ 15 ] might explain the frequent coexistence of the two diseases. For this reason, the common treatment with TMZ and antiseizure medications is very likely.…”

Section: Introductionmentioning

confidence: 99%

Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs

Borowicz-Reutt

Banach

2022

IJMS

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Trimetazidine (TMZ), an anti-ischemic drug for improving cellular metabolism, is mostly administered to patients with poorly controlled ischemic heart disease (IHD). Since IHD is considered the most frequent causative factor of cardiac arrhythmias, and these often coexist with seizure disorders, we decided to investigate the effect of TMZ in the electroconvulsive threshold test (ECT) and its influence on the action of four first-generation antiepileptic drugs in the maximal electroshock test (MES) in mice. The TMZ (up to 120 mg/kg) did not affect the ECT, but applied at doses of 20–120 mg/kg it decreased the antielectroshock action of phenobarbital. The TMZ (50–120 mg/kg) reduced the effect of phenytoin, and, when administered at a dose of 120 mg/kg, it diminished the action of carbamazepine. All of these revealed interactions seem to be pharmacodynamic, since the TMZ did not affect the brain levels of antiepileptic drugs. Furthermore, the combination of TMZ with valproate (but not with other antiepileptic drugs) significantly impaired motor coordination, evaluated using the chimney test. Long-term memory, assessed with a passive-avoidance task, was not affected by either the TMZ or its combinations with antiepileptic drugs. The obtained results suggest that TMZ may not be beneficial as an add-on therapy in patients with IHD and epilepsy.

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Section: Introductionmentioning

confidence: 99%

Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs

Borowicz-Reutt

Banach

2022

IJMS

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“…The use of non-antiepileptic medicines as adjuvant agents, which have anticonvulsant properties and enhance the effects of classical AEDs, is gaining more comprehensive application. Such medicines include, in particular, non-steroidal anti-inflammatory medicines, sodium channel blockers (in particular, lidocaine), slow calcium channel blockers, β-blockers, the If-channel blocker ivabradine, the competitive xanthine oxidase inhibitor allopurinol, statins, selective phosphodiesterase-5 inhibitors (sildenafil, tadalafil), the cardiac glycoside digoxin [5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

SGLT-2 inhibitors as potential anticonvulsants: empagliflozin, but not dapagliflozin, renders a pronounced effect and potentiates the sodium valproate activity in pentylenetetrazole-induced seizures

Tsyvunin

Shtrygol

Havrylov

et al. 2022

SR: PS

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On the way to the search for effective adjuvant medicines for epilepsy treatment, antidiabetic medicines such as sodium-glucose cotransporter-2 inhibitors, which are expressed not only in the kidneys but also in the brain, attract attention. From previous studies, it is known that dapagliflozin improves electroencephalographic parameters in rats on the model of pentylenetetrazole-induced seizures. However, the anticonvulsant potential of other medicines from this group needs to be clarified. The aim of the study is to estimate the effect of empagliflozin, dapagliflozin per se and their combinations with sodium valproate on pentylenetetrazole-induced seizures, as well as on muscle tone and motor coordination in mice. Material and methods. 42 random-bred male albino mice weighing 24-28 g were used in the experiments. Empagliflozin (20 mg/kg) and dapagliflozin (50 mg/kg) were administered intragastrically for 3 days. The classic anticonvulsant sodium valproate (150 mg/kg) per se, in combination with the medicines mentioned above, was administered in a similar regimen. On the second day, 30 minutes after administering all medicines, their effect on muscle tone and coordination of movements was determined in the rotarod test. On the third day, 30 minutes after the last administration of the medicines, their effect on pentylenetetrazole-induced (80 mg/kg subcutaneously) seizures was studied. Results. For the first time, a pronounced anticonvulsant effect of empagliflozin was established both when used alone (a significant increase in latency of the convulsions and a decrease in lethality by 43 %) and especially in combination with sodium valproate (a significant increase in latency of the convulsions, a decrease in the number and severity of seizures and a decrease in lethality by 83 %), as well as the absence of a muscle relaxant effect in both cases. Dapagliflozin has neither its anticonvulsant properties nor its effect on the action of sodium valproate. However, this medicine caused muscle relaxation, especially when combined with sodium valproate. Conclusions. The results suggest that empagliflozin, unlike dapagliflozin, has a high potential as an adjuvant medicine in treating epilepsy, as it enhances the efficacy of the classic anticonvulsant sodium valproate without muscle relaxant side effects

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“…One of the ways to solve this problem is to use non-antiepileptic drugsmedicines, that are not classical antiepi leptic drugs (AEDs), but belong to other pharmacological groups and can be used as adjuvants. It was found that the vast majority of antiarrhythmic drugs such as sodium channel blockers (lidocaine), as well as calcium channel blockers (nifedipine, amlodipine, cinnarizine, diltiazem, verapamil) and β-blockers (propranolol, metoprolol, pindolol) have an anticonvulsant effect, which was revealed in several models of seizures in animals, and for individual drugs -in the clinic [5][6][7]. Anticonvulsant properties are also inherent in ivabradine as a blocker of I f -channels of the sinus node, used in the treatment of angina pectoris [8].…”

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confidence: 99%

Effect of digoxin, sodium valproate, their combination and celecoxib on neuroactive amino acids content and cerebral Na+, K+-ATPase activity in pentylenetetrazole-kindled mice

Цивунін,

Штриголь,

Горбач

2023

Фармакологія та лікарська токсикологія

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Our previous studies have shown moderate anticonvulsant efficiency of celecoxib as well as high efficiency of the combination of digoxin at subcardiotonic dose with widespread antiepileptic drugs at a sub- effective doses in various models of primary-generalized chemoinduced seizures. The aim of the study was to determine the efficiency of these medicines in the model of chronic epileptogenesis and the possible neurochemical mechanism of anticonvulsant action of digoxin and celecoxib per se as well as the combination of digoxin with sodium valproate. For this purpose, the effect on the course of pentylenetetrazole (PTZ) kindling, on the content of neurotransmitter amino acids (GABA, glycine, glutamate, aspartate) and the activity of Na+, K+-ATPase in the mice brain has been determined. PTZ kindling was chosen to its maximal pathogenetic similarity to human epilepsy. A total of 56 adult random-bred female albino mice weighing 20–24 g have been chosen. PTZ-induced kindling was simulated by the use of PTZ at a dose of 30 mg/kg intraperitoneally for 16 days. The classic antiepileptic drug sodium valproate has been used at a subeffective dose (1/2 ED50) of 150 mg/kg intra- gastrically. Digoxin was administered subcutaneously at a previously determined effective anticonvulsant dose of 0.8 mg/kg which is equal to 1/10 LD50. Animals of the combination group of digoxin and sodium valproate received drugs in the above-mentioned doses. Celecoxib as an anti-inflammatory agent capable of exhibiting anticonvulsant properties was administered at a dose of 4 mg/kg intragastrically. Sodium valproate and celecoxib were administered 30 minutes and digoxin – 15 min before PTZ administration. The content of GABA, aspartate, glutamate in the brain homogenate was determined by high-voltage electro- phoresis. Glycine content was determined by thin layer chromatography. Тhe activity of Na+, K+-ATPase was determined in the synaptosomal membranes. For 16 days, celecoxib did not affect the clinical course of kindling, when sodium valproate and digoxin per se showed moderate efficacy, and the combination of valproate + digoxin had a complete protective effect against spontaneous seizures. It has been found a statistically significant decrease in the content of GABA, glycine and increase in the content of glutamate, aspartate, as well as almost twofold decrease in Na+, K+-ATPase in the brains of untreated animals. All studied medicines (to a lesser extent – celecoxib, most pronounced – valproate + digoxin) contributed to the normalization of the balance of neurotrans- mitter amino acids. All drugs, except digoxin per se, significantly increased the activity of Na+, K+-ATPase (valproate + digoxin maximally). Therefore, the combination of sodium valproate with digoxin in terms of the effectiveness of seizure control and the influence on neurochemical mechanisms of neuronal excitability control significantly exceeded the effect of these drugs per se and celecoxib. The pronounced potentiation of the anticonvulsant activity of sodium valproate with digoxin determines the feasibility of further in-depth study of the mechanisms of action of this combination as a promising approach to the epilepsy treatment.

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Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action—A Critical Review of Experimental Findings

Cited by 6 publications

References 77 publications

Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs

Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs

SGLT-2 inhibitors as potential anticonvulsants: empagliflozin, but not dapagliflozin, renders a pronounced effect and potentiates the sodium valproate activity in pentylenetetrazole-induced seizures

Effect of digoxin, sodium valproate, their combination and celecoxib on neuroactive amino acids content and cerebral Na+, K+-ATPase activity in pentylenetetrazole-kindled mice

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