Anti-Epileptogenic Effects of Antiepileptic Drugs

• Published in: International journal of molecular sciences Vol. 21; no. 7; p. 2340
• Main Authors: Miziak, Barbara, Konarzewska, Agnieszka, Ułamek-Kozioł, Marzena, Dudra-Jastrzębska, Monika, Pluta, Ryszard, Czuczwar, Stanisław J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.03.2020; MDPI
• Subjects: Animal models; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antiepileptic agents; antiepileptic drugs; Benzodiazepines; Brain damage; Brain injury; Convulsions & seizures; Diazepam; Drugs; Epilepsy; Epilepsy - drug therapy; Epilepsy - epidemiology; Epilepsy - pathology; epileptogenesis; Etiracetam; Gabapentin; Growth factors; Humans; Neurodegeneration; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Review; Seizures; Seizures - drug therapy; Seizures - pathology; status epilepticus; Status Epilepticus - drug therapy; Status Epilepticus - pathology; Topiramate; Valproic acid; epilepsy; antiepileptic drugs; status epilepticus; seizures; epileptogenesis; neuroprotection
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21072340

Generally, the prevalence of epilepsy does not exceed 0.9% of the population and approximately 70% of epilepsy patients may be adequately controlled with antiepileptic drugs (AEDs). Moreover, status epilepticus (SE) or even a single seizure may produce neurodegeneration within the brain and SE has been recognized as one of acute brain insults leading to acquired epilepsy via the process of epileptogenesis. Two questions thus arise: (1) Are AEDs able to inhibit SE-induced neurodegeneration? and (2) if so, can a probable neuroprotective potential of particular AEDs stop epileptogenesis? An affirmative answer to the second question would practically point to the preventive potential of a given neuroprotective AED following acute brain insults. The available experimental data indicate that diazepam (at low and high doses), gabapentin, pregabalin, topiramate and valproate exhibited potent or moderate neuroprotective effects in diverse models of SE in rats. However, only diazepam (at high doses), gabapentin and pregabalin exerted some protective activity against acquired epilepsy (spontaneous seizures). As regards valproate, its effects on spontaneous seizures were equivocal. With isobolography, some supra-additive combinations of AEDs have been delineated against experimental seizures. One of such combinations, levetiracetam + topiramate proved highly synergistic in two models of seizures and this particular combination significantly inhibited epileptogenesis in rats following status SE. Importantly, no neuroprotection was evident. It may be strikingly concluded that there is no correlation between neuroprotection and antiepileptogenesis. Probably, preclinically verified combinations of AEDs may be considered for an anti-epileptogenic therapy.