Selected Molecular Targets for Antiepileptogenesis
The term epileptogenesis defines the usually durable process of converting normal brain into an epileptic one. The resistance of a significant proportion of patients with epilepsy to the available pharmacotherapy prompted the concept of a causative treatment option consisting in stopping or modifyin...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| author | Marek J. Pawlik Barbara Miziak Aleksandra Walczak Agnieszka Konarzewska Magdalena Chrościńska-Krawczyk Jan Albrecht Stanisław J. Czuczwar |
| author_facet | Marek J. Pawlik Barbara Miziak Aleksandra Walczak Agnieszka Konarzewska Magdalena Chrościńska-Krawczyk Jan Albrecht Stanisław J. Czuczwar |
| author_sort | Marek J. Pawlik |
| collection | DOAJ |
| description | The term epileptogenesis defines the usually durable process of converting normal brain into an epileptic one. The resistance of a significant proportion of patients with epilepsy to the available pharmacotherapy prompted the concept of a causative treatment option consisting in stopping or modifying the progress of epileptogenesis. Most antiepileptic drugs possess only a weak or no antiepileptogenic potential at all, but a few of them appear promising in this regard; these include, for example, eslicarbazepine (a sodium and T-type channel blocker), lamotrigine (a sodium channel blocker and glutamate antagonist) or levetiracetam (a ligand of synaptic vehicle protein SV2A). Among the approved non-antiepileptic drugs, antiepileptogenic potential seems to reside in losartan (a blocker of angiotensin II type 1 receptors), biperiden (an antiparkinsonian drug), nonsteroidal anti-inflammatory drugs, antioxidative drugs and minocycline (a second-generation tetracycline with anti-inflammatory and antioxidant properties). Among other possible antiepileptogenic compounds, antisense nucleotides have been considered, among these an antagomir targeting microRNA-134. The drugs and agents mentioned above have been evaluated in post-status epilepticus models of epileptogenesis, so their preventive efficacy must be verified. Limited clinical data indicate that biperiden in patients with brain injuries is well-tolerated and seems to reduce the incidence of post-traumatic epilepsy. Exceptionally, in this regard, our own original data presented here point to c-Fos as an early seizure duration, but not seizure intensity-related, marker of early epileptogenesis. Further research of reliable markers of early epileptogenesis is definitely needed to improve the process of designing adequate antiepileptogenic therapies. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:36:54Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-94ccc383089040f2b73c369c139c70eb2023-11-22T13:26:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218973710.3390/ijms22189737Selected Molecular Targets for AntiepileptogenesisMarek J. Pawlik0Barbara Miziak1Aleksandra Walczak2Agnieszka Konarzewska3Magdalena Chrościńska-Krawczyk4Jan Albrecht5Stanisław J. Czuczwar6Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, PolandDepartment of Pathophysiology, Medical University of Lublin, 20-090 Lublin, PolandDepartment of Pathophysiology, Medical University of Lublin, 20-090 Lublin, PolandDepartment of Pathophysiology, Medical University of Lublin, 20-090 Lublin, PolandDepartment of Child Neurology, Medical University of Lublin, 20-093 Lublin, PolandDepartment of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, PolandDepartment of Pathophysiology, Medical University of Lublin, 20-090 Lublin, PolandThe term epileptogenesis defines the usually durable process of converting normal brain into an epileptic one. The resistance of a significant proportion of patients with epilepsy to the available pharmacotherapy prompted the concept of a causative treatment option consisting in stopping or modifying the progress of epileptogenesis. Most antiepileptic drugs possess only a weak or no antiepileptogenic potential at all, but a few of them appear promising in this regard; these include, for example, eslicarbazepine (a sodium and T-type channel blocker), lamotrigine (a sodium channel blocker and glutamate antagonist) or levetiracetam (a ligand of synaptic vehicle protein SV2A). Among the approved non-antiepileptic drugs, antiepileptogenic potential seems to reside in losartan (a blocker of angiotensin II type 1 receptors), biperiden (an antiparkinsonian drug), nonsteroidal anti-inflammatory drugs, antioxidative drugs and minocycline (a second-generation tetracycline with anti-inflammatory and antioxidant properties). Among other possible antiepileptogenic compounds, antisense nucleotides have been considered, among these an antagomir targeting microRNA-134. The drugs and agents mentioned above have been evaluated in post-status epilepticus models of epileptogenesis, so their preventive efficacy must be verified. Limited clinical data indicate that biperiden in patients with brain injuries is well-tolerated and seems to reduce the incidence of post-traumatic epilepsy. Exceptionally, in this regard, our own original data presented here point to c-Fos as an early seizure duration, but not seizure intensity-related, marker of early epileptogenesis. Further research of reliable markers of early epileptogenesis is definitely needed to improve the process of designing adequate antiepileptogenic therapies.https://www.mdpi.com/1422-0067/22/18/9737epileptogenesisantiepileptic drugslosartannonsteroidal anti-inflammatory drugsantioxidative drugsantagomirs |
| spellingShingle | Marek J. Pawlik Barbara Miziak Aleksandra Walczak Agnieszka Konarzewska Magdalena Chrościńska-Krawczyk Jan Albrecht Stanisław J. Czuczwar Selected Molecular Targets for Antiepileptogenesis International Journal of Molecular Sciences epileptogenesis antiepileptic drugs losartan nonsteroidal anti-inflammatory drugs antioxidative drugs antagomirs |
| title | Selected Molecular Targets for Antiepileptogenesis |
| title_full | Selected Molecular Targets for Antiepileptogenesis |
| title_fullStr | Selected Molecular Targets for Antiepileptogenesis |
| title_full_unstemmed | Selected Molecular Targets for Antiepileptogenesis |
| title_short | Selected Molecular Targets for Antiepileptogenesis |
| title_sort | selected molecular targets for antiepileptogenesis |
| topic | epileptogenesis antiepileptic drugs losartan nonsteroidal anti-inflammatory drugs antioxidative drugs antagomirs |
| url | https://www.mdpi.com/1422-0067/22/18/9737 |
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