REVIEW PAPER
Neuroprotective effects of some newer and potential antiepileptic drugs
1
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
2
Department of Pathophysiology, Skubiszewski Medical University, Poland
3
Department of Neurological Diseases, Institute of Medical Education, Kielce
4
Department of Neurology, Neuropsychiatric Hospital, Kielce, Poland
J Pre Clin Clin Res. 2007;1(1):1–5
KEYWORDS
ABSTRACT
Experimental models of epilepsy or status epilepticus (SE) provide evidence that seizures result in diffuse brain damage. Other neurological conditions are also associated with neurodegeneration, for example, stroke, head injury and chronic neurodegenerative diseases. In this review, the neuroprotective effects of a number of newer or potential antiepileptic drugs (AEDs) are considered in general in models of experimental epilepsy and ischemia. Among newer AEDs, felbamate, gabapentin, tiagabine and topiramate proved to be neuroprotective agents against seizure, or ischemia-generated neuronal death. The same profile of activity was presented by a potential AED, talampanel. Vigabatrin and levetiracetam were effective against ischemia-induced neurodegeneration, while their effects in seizure models were less consistent. It may be assumed that the neuroprotective effects of AEDs in models of epilepsy or SE may prevent continuous progression of epileptogenesis, thus improving the condition of epileptic patients. However, this possible association may not be that clear. There are data indicating that in spite of clear-cut neuroprotection in models of SE, the subsequent occurrence of spontaneous seizure activity was not prevented. There is also no significant correlation between neuroprotection in experimental ischemia and clinical data. Neuroprotection afforded by AEDs is evident. However, it is not still clear whether this can have a clinically relevant potential. The available clinical data on brain ischemia and AEDs are not encouraging. So far, there are no clinical data whether the neuroprotective effects of AEDs in experimental models of epilepsy possess any impact on the severity of epilepsy. It is possible that AEDs will prove effective in some chronic neurodegenerative diseases.
REFERENCES (40)
1.
Czuczwar SJ, Patsalos P: The new generation of GABA-enhancers. Potential in the treatment of epilepsy. CNS Drugs 2001, 15, 339-350.
3.
Klitgaard H, Pitkanen A: Antiepileptogenesis, neuroprotection, and disease modification in the treatment of epilepsy: focus on levetiracetam. Epileptic Disord 2003, 5, 9-16.
4.
Turski WA, Czuczwar SJ, Kleinrok Z, Turski L: Cholinomimetics produce seizures and brain damage in rats. Experientia 1983, 39, 1408-1411.
5.
Fisher A, Wang X, Cock HR, Thom M, Patsalos PN, Walker MC: Synergism between topiramate and budipine in refractory status epilepticus in the rat. Epilepsia 2004, 45, 1300-1307.
6.
Vajda FJE: Neuroprotection and neurodegenerative disease. J Clin Neurosci 2002, 9, 4-8.
7.
Trojnar MK, Malek R, Chrościńska M, Nowak S, Błaszczyk B, Czuczwar SJ: Neuroprotective effects of antiepileptic drugs. Pol J Pharmacol 2002, 54, 557-566.
8.
Urbańska E, Czuczwar SJ, Kleinrok Z, Turski WA: Excitatory amino acids in epilepsy. Restor Neurol Neurosci 1998, 13, 25-39.
9.
Pitkanen A: Treatment with antiepileptic drugs: possible neuroprotective effects. Neurology 1996, 47, 12-16.
10.
Sloviter RS: Calcium-binding protein (calbindin-D28k) and parvalbumin immunocytochemistry: localization in the rat hippocampus with specific reference to the selective vulnerability of hippocampal neurons to seizure activity. J Comp Neurol 1989, 280, 183-196.
11.
Bittigau P, Ikonomidou C: Glutamate in neurologic diseases. J Child Neurol 1997, 12, 471-485.
12.
Czapiński P, Błaszczyk B, Czuczwar SJ: Mechanisms of action of antiepileptic drugs. Curr Top Med Chem 2005, 5, 3-14.
13.
Bialer M, Johannessen JC, Kupferberg HJ,Levy RH, Loiseau P, Perucca E: Progress report on new antiepileptic drugs: a summary of the 6th Eilat Conference (EILAT VI). Epilepsy Res 2002, 51, 31-71.
14.
French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, Theodore WH, Bazil C, Stern J, Schachter SC, Bergen D, Hirtz D, Montouris GD, Nespeca M, Gidal B, Marks WJ Jr, Turk WR, Fischer JH, Bourgeois B, Wilner A, Faught RE Jr, Sachdeo RC, Beydoun A, Glauser TA: Efficacy and tolerability of the new antiepileptic drugs II: Ttreatment of refractory epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2004, 62, 1261-1273.
15.
Rekling JC: Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation Neurosci Lett 2003, 335, 167-170.
16.
Pitkanen A: Efficacy of current antiepileptics to prevent neurodegeneration in epilepsy models. Epilepsy Res 2002, 50, 141-160.
17.
Lynch B, Lambeng N, Nocka K, Kensel-Hammes P, Bajjellieh SM, Matagne A, Fuks B: The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci 2004, 101, 9861-9866.
18.
Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T: Progress report on new antiepileptic drugs: a summary of the 7th Eilat Conference (EILAT VII). Epilepsy Res 2004, 61, 1-48.
19.
Lagae L, Buyse G, Deconinck A, Ceulemans B: Effect of levetiracetam in refractory chilhood epilepsy syndromes. Eur J Pediatr Neurol 2003, 7, 123–128.
20.
Patsalos PN: Properties of antiepileptic drugs in the treatment of idiopathic generalized epilepsies. Epilepsia 2005,46 (Suppl. 9), 140- 148.
21.
Mazarati AM, Baldwin R, Klitgaard H, Matagne A, Wasterlain CG: Anticonvulsant effects of levetiracetam and levetiracetam–diazepam combinations in experimental status epilepticus. Epilepsy Res 2004, 58, 167–174.
22.
Leker RR, Neufeld MY: Anti-epileptic drugs as possible neuroprotectants in cerebral ischemia. Brain Res 2003, 42, 187-203.
23.
Ben-Menachem E: Pregabalin pharmacology and its relevance to clinical practice. Epilepsia 2004, 45 (Suppl. 6), 13-18.
24.
Chappell AS, Sander JW, Brodie MJ, Chadwick D, Lledo A, Zhang D, Bjerke J, Kiesler GM, Arroyo S: A crossover, add-on trial of talampanel in patients with refractory partial seizures. Neurology 2002, 58, 1680- 1682.
25.
Vilagi I, Takacs J, Gulyas-Kovacs A, Banczerowski-Pelyhe I, Tarnawa I: Protective effect of the antiepileptic drug candidate talampanel against AMPA-induced striatal neurotoxicity in neonatal rats. Brain Res Bull 2002, 59, 35-40.
26.
Lodge D, Bond A, O’Neill M, Hicks CA, Jones MG: Stereoselective effects of 2,3 benzodiazepines in vivo: Electrophysiology and neuroprotection studies. Neuropharmacology 1996, 35, 1681-1688.
27.
Niebauer M, Gruenthal M: Topiramate reduces neuronal injury after experimental status epilepticus. Brain Res 1999, 837, 263-269.
28.
Rigoulot MA, Koning E, Ferrandon A, Nehlig A: Neuroprotective properties of topiramate in the lithium-pilocarpine model of epilepsy. J Pharmacol Exp Ther 2004, 308, 787-795.
29.
Follett PL, Deng W, Dai W, Talos D M, Massillon L J, Rosenberg PA, Volpe JJ, Jensen FE: Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: A protective role for topiramate. J Neurosci 2004, 24, 4412-4420.
30.
Schwabe K, Ebert E, Loscher W: Bilateral microinjections of vigabatrin in the central piriform cortex retard amygdala kindling in rats. Neuroscience 2004, 129, 425-429.
31.
Mitchell WG, Shah NS: Vigabatrin for infantile spasms. Pediatr Neurol 2002, 27, 161-164.
32.
Weinberger JM: Evolving therapeutic approaches to treating acute ischemic stroke. J Neurol Sci 2006, 249, 101-109.
33.
Czuczwar SJ, Turski L, Kleinrok Z: Effects of some antiepileptic drugs in pentetrazol-induced convulsions in mice lesioned with kainic acid. Epilepsia 1981, 22, 407-414.
34.
Czuczwar SJ, Turski L, Turski W, Kleinrok Z: Anticonvulsant action of phenobarbital, diazepam, carbamazepine, and diphenylhydantoin in the electroshock test in mice after lesion of hippocampal pyramidal cells with intracecerbroventricular kainic acid. Epilepsia 1982, 23, 377- 382.
35.
Brandt C, Potschka H, Loscher W, Ebert U: N-methyl-D-aspartate receptor blockade after status epilepticus protects against limbic brain damage but not against epilepsy in the kainate model of temporal lobe epilepsy. Neuroscience 2003, 118, 727-740.
36.
Murata M, Haneqawa K, Kanazawa I: The Japan Zonisamide on PD study group: Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology 2007, 68, 45-50.
37.
Wu SS, Frucht SJ: Treatment of Parkinsons’s disease; what’s on the horizon? CNS Drugs 2005, 19, 723-743.
38.
de Tommaso M, Di Fruscolo O, Sciruicchio V, Specchio N, Cormio C, De Caro MF, Livrea P: Efficacy of levetiracetam in Huntington’s disease. Clin Neuropharmacol 2005, 28, 280-284.
39.
Bittigau T, Sifringer M, Ikonomidou C: Antiepileptic drugs and apoptosis in the developing brain. Ann NY Acad Sci 2003, 993, 103- 114.
40.
Glier C, Dzietko M, Bittigau P, Jarosz B, Korobowicz E, Ikonomidou C: Therapeutic doses of topiramate are not toxic to the developing rat brain. Exp Neurol 2004, 187, 403-409.
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