Digoxin enhances the effect of antiepileptic drugs with different mechanism of action in the pentylenetetrazole-induced seizures in mice

Tsyvunin, Vadim; Shtrygol, S. Yu.; Shtrygol, Diana

doi:10.1016/j.eplepsyres.2020.106465

Cited by 15 publications

(13 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ó ïåðø³é ñåð³¿ åêñïåðèìåíò³â îö³íþâàëè âïëèâ ñåðöåâèõ ´ë³êîçèä³â íà ïåðåá³ã ìîäåëüíèõ ñóäîì ó ç³ñòàâëþâàíèõ äîçàõ, ùî ñêëàäàþòü ïðèáëèçíî 1 / 10 LD 50 [3,14] äëÿ â³ä-ïîâ³äíîãî ïðåïàðàòó. Ñåðöåâ³ ´ë³êîçèäè, ùî âèïóñêàþòüñÿ ó ôîðì³ ðîç÷èí³â äëÿ ³í'ºêö³é, ââîäèëè îäíîêðàòíî ï³äøê³ðíî (ï/ø) çà 15 õâ äî ìîäåëþâàííÿ ñóäîì: äèãîêñèí ("Äèãîêñèí", ðîç÷èí äëÿ ³í'ºêö³é, 0,25 ì´/ìë, ÒÎÂ "Äîñë³äíèé çàâîä "ÃÍÖËÑ" / ÒÎÂ "Ôàðìà-öåâòè÷íà êîìïàí³ÿ "Çäîðîâ'ÿ", Óêðà¿íà) -ó äî-ç³ 0,8 ì´/ê´, äëÿ ÿêî¿ âaeå äîâåäåíî ïðîòèñóäîìíó ä³þ [14,17]; ñòðîôàíòèí G ("Ñòðîôàíòèí-Ã", ðîç÷èí äëÿ ³í'ºêö³é, 0,25 ì´/ìë, ÒÎÂ "Äîñë³äíèé çàâîä "ÃÍÖËÑ" / ÒÎÂ "Ôàðìà-öåâòè÷íà êîìïàí³ÿ "Çäîðîâ'ÿ", Óêðà¿íà) -ó äî-ç³ 0,8 ì´/ê´; êîðãë³êîí ("Êîðãë³êîí", ðîç÷èí äëÿ ³í'ºêö³é, 0,6 ì´/ìë, ÒÎÂ "Äîñë³äíèé çàâîä "ÃÍÖËÑ" / ÒÎÂ "Ôàðìàöåâòè÷íà êîìïàí³ÿ "Çäîðîâ'ÿ", Óêðà¿íà) -ó äîç³ 1 ì´/ê´. Ëàíàòîçèä Ñ ("Öåëàí³ä", òàáëåòêè, 0,25 ì´, ÒÎÂ "Äîñë³äíèé çàâîä "ÃÍÖËÑ", Óêðà¿íà) ó âèãëÿä³ âîäíîãî ðîç÷èíó ââîäèëè îäíîðàçîâî âíóòð³øíüîøëóíêîâî (â/ø) ó äîç³ 0,8 ì´/ê´ çà 30 õâ äî ³íäóêö³¿ åêñïåðèìåíòàëüíèõ ñóäîì.…”

Section: ìàòåð³àë ³ ìåòîäèunclassified

“…Ó äðóã³é ñåð³¿ äîñë³ä³â âèêîðèñòîâóâàëè ïðåïàðàò-ë³äåð, ÿêèì âèÿâèâñÿ äèãîêñèí, ó øèðîêîìó ä³àïàçîí³ äîç â³ä 0,2 äî 1,6 ì´/êḉ à ï/ø øëÿõó ââåäåííÿ. Ñóäîìíèé à´åíò -ïåíòèëåíòåòðàçîë (Sigma, ÑØÀ) -ó âèãëÿä³ âîäíîãî ðîç÷èíó ââîäèëè òâàðèíàì ï/ø ó äîç³ 80 ì´/ê´ [7,17]. Îäðàçó ï³ñëÿ ââåäåííÿ êîíâóëüñàíòà ìèøåé âì³ùóâàëè â ³íäèâ³äóàëüí³ ïðîçîð³ ïëàñòèêîâ³ öèë³íäðè÷í³ áîêñè ä³àìåòðîì 15 ñì òà âèñîòîþ 30 ñì ³ áåçïåðåðâíî ñïîñòåð³ãàëè ïðîòÿãîì 60 õâ.…”

Section: ìàòåð³àë ³ ìåòîäèunclassified

“…Âèðàçí³ñòü ïðîòèñóäîìíî¿ ä³¿ ïðå-ïàðàò³â òà ¿õ êîìá³íàö³é îö³íþâàëè çà òàêèìè ïîêàçíèêàìè: ëàòåíòíèé ïåð³îä ïîÿâè ïåðøèõ êîíâóëüñ³é, ê³ëüê³ñòü êëîí³êî-òîí³÷íèõ ïàðî-êñèçì³â íà 1 ìèøó, % òâàðèí ó ãðóï³ îêðåìî ç êëîí³÷íèìè òà òîí³÷íèìè íàïàäàìè, òÿaeê³ñòü ñóäîì ó áàëàõ (1 áàë -ïîîäèíîê³ çäðèãàííÿ, 2 áàëè -"ìàíåaeíèé" á³ã àáî ñò³éêà ó ïîç³ "êåíãóðó", 3 áàëè -êëîí³÷í³ ñóäîìè áåç á³÷íîãî ïîëîaeåííÿ, 4 áàëè -êëîí³êî-òîí³÷í³ ñóäîìè ç á³÷íèì ïîëîaeåííÿì, 5 áàë³â -òîí³÷íà åêñòåí-ç³ÿ, 6 áàë³â -òîí³÷íà åêñòåíç³ÿ, ùî ïðèçâåëà äî çàãèáåë³ òâàðèíè), òðèâàë³ñòü ñóäîìíîãî ïåð³îäó, ÷àñ aeèòòÿ òâàðèí äî çàãèáåë³ òà ëå-òàëüí³ñòü. Ó âèïàäêó, ÿêùî ñóäîìè íå ñïîñòå-ð³ãàëè ïðîòÿãîì 1 ãîä, ââàaeàëè, ùî ëàòåíòíèé ïåð³îä äîð³âíþº 60 õâ [17].…”

Section: ìàòåð³àë ³ ìåòîäèunclassified

“…[2,22], íåñòåðî¿äíèõ ïðîòèçàïàëüíèõ ïðåïàðàò³â [5,16], ñèíòåòè÷íèõ ïðîòèä³àáå-òè÷íèõ çàñîá³â [6,20], ñòàòèí³â [11,13] òîùî. Îêð³ì òîãî, íàÿâí³ åêñïåðèìåíòàëüí³ îá´ðóíòóâàííÿ ïîòåíö³þâàííÿ íèçüêèìè äîçàìè ñåðöåâîãî ´ë³êîçèäó äèãîêñèíó åôåêòó íèçêè ÏÅÇ ó ñóáåôåêòèâíèõ äîçàõ [17]. Îòðèìàíî òàêîae êë³í³÷í³ äàí³ ïðî åôåêòèâí³ñòü ñóáêàð-ä³îòîí³÷íèõ äîç äèãîêñèíó ÿê çàñòîñîâàíîãî ó ôîðìàò³ off-label àä'þâàíòíîãî çàñîáó ó ïà-ö³ºíò³â ³ç ïîë³ôàðìàêîðåçèñòåíòíîþ åï³ëåï-ñ³ºþ [14].…”

mentioning

confidence: 99%

See 3 more Smart Citations

Anticonvulsive potential of cardiac glycosides under conditions of pentilentetrazole-induced seizures in mice: comparative study

Tsyvunin

Shtrygol

et al. 2021

AML

View full text Add to dashboard Cite

Aim. The research provides a comparative analysis of the possible anticonvulsant action of different cardiac glycosides, namely: digoxin, lanatoside C, strophanthin G and corglycone. In addition, it detrmines the leading medication among the abovementioned ones by dose-dependence of its anticonvulsant action. Material and Methods. The research was performed on 66 random-bred albino male mice. The anticonvulsant effect of cardiac glycosides was studied in a baseline model of pentylenetetrazole-induced seizures. The first series of experiment evaluated the effect of cardiac glycosides on the course of model seizures in comparable doses of approximately 1/10 LD50 for the corresponding drug: digoxin, lanatoside C and strophanthin G - at a dose of 0.8 mg/kg; corglycone - at a dose of 1 mg/kg. The second series of experiments used the drug-leader, which was digoxin, in a wide dose range from 0.2 to 1.6 mg/kg. Digoxin, strophanthin G and corglycone were administered subcutaneously for 15 minutes, lanatoside C - intragastrically for 30 minutes before the induction of experimental seizures. Convulsive agent - pentylenetetrazole in the form of an aqueous solution was administered to animals subcutaneously at a dose of 80 mg/kg. Results and Discussion. Digoxin at a dose of 0.8 mg/kg under conditions of pentylenetetrazole-induced seizures shows a pronounced anticonvulsant activity: it is the only one among the studied cardiac glycosides that probably reduces lethality. In addition, digoxin prolongs the latency period of the first attacks, and reduces the number of clonic-tonic paroxysms in 1 mouse. Moderate anticonvulsant properties of lanatoside C were found both by a statistically significant decrease in the number of clonic-tonic seizures in 1 mouse, and by a significant reduction in the duration of the convulsive period. Although strophanthin G is unlikely to affect lethality, it moderately reduces the severity of pentylenetetrazole-induced seizures in mice, as evidenced by a statistically significant prolongation of the latency period of the first seizures, as well as a decrease in the number of clonic-tonic seizures in 1 mouse and the duration of seizures. Prophylactic administration of corglycone only prolongs the latency period of seizures and significantly reduces the number of clonic-tonic seizures in 1 mouse. The results of the dose-dependence study of digoxin anticonvulsant action show a clear anticonvulsant potential of this cardiac glycoside in a wide range of doses - from 0.2 to 1.6 mg/kg - with a maximum effect at a dose of 0.8 mg/kg. Conclusions. It was found that cardiac glycosides have a different severity of anticonvulsant effect: the most powerful anticonvulsant effect is due to digoxin, lanatoside C and strophanthin G have moderate properties, and the least pronounced effect is characteristic to corglycone. In addition, it was determined that digoxin exhibits anticonvulsant properties in a wide range of doses, and has the most pronounced anticonvulsant effect at a dose of 0.8 mg/kg. The obtained results substantiate the expediency of further in-depth study of digoxin as an anticonvulsant medicine.

show abstract

Section: ìàòåð³àë ³ ìåòîäèunclassified

mentioning

confidence: 99%

See 2 more Smart Citations

Anticonvulsive potential of cardiac glycosides under conditions of pentilentetrazole-induced seizures in mice: comparative study

Tsyvunin

Shtrygol

et al. 2021

AML

View full text Add to dashboard Cite

show abstract

“…One such non-AEDs with previously experimentally and clinically proven anticonvulsant activity is the known cardiac glycoside digoxin at a sub-cardiotonic doses that do not cause side effects [10,11]. 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]. It was found that in the basic models of primary generalized seizuresparoxysms, induced by pentylenetetrazole and maximal electroshock -digoxin in a sub-cardiotonic dose signifi-cantly potentiates the anticonvulsant action of valproate, carbamazepine, levetiracetam, lamotrigine, topiramate, clonazepam and phenobarbital [12,13].…”

Section: Introductionmentioning

confidence: 99%

Low-dose digoxin enhances the anticonvulsive potential of carbamazepine and lamotrigine in chemo-induced seizures with different neurochemical mechanisms

Havrylov

Tsyvunin

Shtrygol

et al. 2021

SR: PS

Self Cite

View full text Add to dashboard Cite

"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

show abstract

Genomic insights into the comorbidity between type 2 diabetes and schizophrenia

Arruda,

Khandaker,

Morris

et al. 2024

Schizophr

View full text Add to dashboard Cite

Multimorbidity represents an increasingly important public health challenge with far-reaching implications for health management and policy. Mental health and metabolic diseases have a well-established epidemiological association. In this study, we investigate the genetic intersection between type 2 diabetes and schizophrenia. We use Mendelian randomization to examine potential causal relationships between the two conditions and related endophenotypes. We report no compelling evidence that type 2 diabetes genetic liability potentially causally influences schizophrenia risk and vice versa. Our findings show that increased body mass index (BMI) has a protective effect against schizophrenia, in contrast to the well-known risk-increasing effect of BMI on type 2 diabetes risk. We identify evidence of colocalization of association signals for these two conditions at 11 genomic loci, six of which have opposing directions of effect for type 2 diabetes and schizophrenia. To elucidate these colocalizing signals, we integrate multi-omics data from bulk and single-cell gene expression studies, along with functional information. We identify putative effector genes and find that they are enriched for homeostasis and lipid-related pathways. We also highlight drug repurposing opportunities including N-methyl-D-aspartate (NMDA) receptor antagonists. Our findings provide insights into shared biological mechanisms for type 2 diabetes and schizophrenia, highlighting common factors that influence the risk of the two conditions in opposite directions and shedding light on the complex nature of this comorbidity.

show abstract

Digoxin enhances the effect of antiepileptic drugs with different mechanism of action in the pentylenetetrazole-induced seizures in mice

Cited by 15 publications

References 26 publications

Anticonvulsive potential of cardiac glycosides under conditions of pentilentetrazole-induced seizures in mice: comparative study

Anticonvulsive potential of cardiac glycosides under conditions of pentilentetrazole-induced seizures in mice: comparative study

Low-dose digoxin enhances the anticonvulsive potential of carbamazepine and lamotrigine in chemo-induced seizures with different neurochemical mechanisms

Genomic insights into the comorbidity between type 2 diabetes and schizophrenia

Contact Info

Product

Resources

About