Differential Pharmacokinetic Interplay of Atorvastatin on Lacosamide and Levetiracetam on Experimental Convulsions in Mice
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: The beneficial effects of statins, other than their hypocholesterolemia role, have been well documented, however, their use as an adjuvant drug with other antiseizure drugs, in the treatment of epilepsy is poorly understood.
OBJECTIVE: This study aimed to investigate the symbiotic effect of ATOR along with either lacosamide (LACO) or levetiracetam (LEVE) on experimentally induced epilepsy (Maximal electro-shock-MES or pentylenetetrazol- PTZ) in mice models.
METHODS: Conventional elevated-maze (EPM) and rotarod methods were performed to observe the behavioral effects.
RESULTS: In both the animal models, we found that co-administration of ATOR along with LACO showed a significant reduction in hind-limb extension (HLE) and clonic convulsion (CC) responses, respectively, but not in the ATOR+LEVE treated group. Intriguingly, comparable Straub tail response and myoclonic convulsion as the diazepam (DIA) group were observed only in the ATOR+LACO treated group. Moreover, a significant muscle-grip strength was observed in both groups. Also, pharmacokinetic analysis has indicated that the mean plasma concentration of ATOR peaked at 2nd hr in the presence of LACO but marginally peaked in the presence of LEVE. An Insilico study has revealed that ATOR has a higher binding affinity toward neuronal sodium channels.
CONCLUSION: This study has demonstrated that the plasma concentration of ATOR was potentiated in the presence of LACO, but not in the presence of LEVE and it has provided significant protection against both the electro and chemo-convulsive models in mice. This could be due to the symbiotic pharmacokinetic interplay of ATOR with LACO, and possibly, this interplay may interfere with sodium channel conductance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Current drug metabolism - 24(2023), 9 vom: 15., Seite 645-655 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rajangam, Jayaraman [VerfasserIn] |
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| Links: |
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| Themen: |
44YRR34555 |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 16.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/0113892002253895231020100743 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364130326 |
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| 245 | 1 | 0 | |a Differential Pharmacokinetic Interplay of Atorvastatin on Lacosamide and Levetiracetam on Experimental Convulsions in Mice |
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| 500 | |a Date Revised 16.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: The beneficial effects of statins, other than their hypocholesterolemia role, have been well documented, however, their use as an adjuvant drug with other antiseizure drugs, in the treatment of epilepsy is poorly understood | ||
| 520 | |a OBJECTIVE: This study aimed to investigate the symbiotic effect of ATOR along with either lacosamide (LACO) or levetiracetam (LEVE) on experimentally induced epilepsy (Maximal electro-shock-MES or pentylenetetrazol- PTZ) in mice models | ||
| 520 | |a METHODS: Conventional elevated-maze (EPM) and rotarod methods were performed to observe the behavioral effects | ||
| 520 | |a RESULTS: In both the animal models, we found that co-administration of ATOR along with LACO showed a significant reduction in hind-limb extension (HLE) and clonic convulsion (CC) responses, respectively, but not in the ATOR+LEVE treated group. Intriguingly, comparable Straub tail response and myoclonic convulsion as the diazepam (DIA) group were observed only in the ATOR+LACO treated group. Moreover, a significant muscle-grip strength was observed in both groups. Also, pharmacokinetic analysis has indicated that the mean plasma concentration of ATOR peaked at 2nd hr in the presence of LACO but marginally peaked in the presence of LEVE. An Insilico study has revealed that ATOR has a higher binding affinity toward neuronal sodium channels | ||
| 520 | |a CONCLUSION: This study has demonstrated that the plasma concentration of ATOR was potentiated in the presence of LACO, but not in the presence of LEVE and it has provided significant protection against both the electro and chemo-convulsive models in mice. This could be due to the symbiotic pharmacokinetic interplay of ATOR with LACO, and possibly, this interplay may interfere with sodium channel conductance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Atorvastatin | |
| 650 | 4 | |a epilepsy | |
| 650 | 4 | |a lacosamide | |
| 650 | 4 | |a levetiracetam | |
| 650 | 4 | |a pentylenetetrazol | |
| 650 | 4 | |a pharmacokinetics. | |
| 650 | 7 | |a Atorvastatin |2 NLM | |
| 650 | 7 | |a A0JWA85V8F |2 NLM | |
| 650 | 7 | |a Levetiracetam |2 NLM | |
| 650 | 7 | |a 44YRR34555 |2 NLM | |
| 650 | 7 | |a Lacosamide |2 NLM | |
| 650 | 7 | |a 563KS2PQY5 |2 NLM | |
| 650 | 7 | |a Anticonvulsants |2 NLM | |
| 700 | 1 | |a Lakshmanan, Arun Prasath |e verfasserin |4 aut | |
| 700 | 1 | |a Palei, Narahari N |e verfasserin |4 aut | |
| 700 | 1 | |a Elumalai, Karthikeyan |e verfasserin |4 aut | |
| 700 | 1 | |a Kotakonda, Muddukrishnaiah |e verfasserin |4 aut | |
| 700 | 1 | |a Prakash, R |e verfasserin |4 aut | |
| 700 | 1 | |a Latha, P |e verfasserin |4 aut | |
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