Abstract
Epilepsy presents an important morbidity rate. Despite of antiepileptic drug a significant group (30%) of patients is refractory. Nowadays it is known that the main cause of this problem is the development of drug resistance, which could be explained by two hypotheses that are matter of multiple studies. One of these hypotheses refers to alterations in anticonvulsants targets (channels and receptors), the other talk about increase in the expression of multi-drugs transporters. The second fact has opened a new field of investigation in pharmaco-genetics, which seems promise a possible solution to this old problem.
References
Devinski O. Patients with refractory seizures. N Eng J Med 1999; 340: 1565 - 1570.
Velez A, Eslava - Cobos J. Epilepsy in Colombia: Epidemiologic profile and classification of epileptic seizures and syndromes. Epilepsia 2006; 47: 193 - 201.
Arroyo S, Brodie MJ, Avanzini G, et al. Is refractory epilepsy preventable? Epilepsia 2002; 43: 437 - 444.
Brodie MJ, French JA. Management of first antiepileptic drug in adolescents and adults. Lancet 2000; 356: 323 - 329.
Brodie MJ. Diagnosing and predicting refractory epilepsy. Acta Neurol Scand 2005; 112 (Suppl. 181): 36 - 39.
French JA. Refractory epilepsy: Clinical overview. Epilepsia 2007; 48(Suppl 1): 3 - 7.
Mann M, Pons G. Various pharmacogenetics aspects of antiepileptic drug therapy: A review. CNS Drgus 2007; 21: 143 - 164.
Siddiqui A, Kerb R, Weale ME, et al. Association of multidrug resistance in epilepsy with polymorphism in the drug - transporter gene ABCB1. N Eng J Med 2003; 348: 1442 - 1448.
Bazil CW, Pedley TA. Clinical pharmacology of antiepileptic drugs. Clin Neuropharmacol 2003; 26: 38 - 52.
Kwan P, Brodie MJ. Potential role pf drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia 2005; 46: 224 - 235.
Glauser TA. Advancing the medical management of epilepsy: disease modification and pharmacogenetics. J Chils Neurol 2001; 17(Suppl. 1): S85 - S93.
Loscher W. Drug transporters in the epileptic brain. Epilepsia 2007; 48(Suppl 1): 8 - 13.
Remy S, Beck H. Molecular and cellular mechanisms of pharmacoresistance in epilepsy. Brain 2006; 129: 18 - 35.
Kohling R. Voltage - gated sodium channels in epilepsy. Epilepsia 2002; 43: 1278 - 1295.
Catterall WA. Molecular properties of brain sodium channels: an important target for anticonvulsant drugs. Adv Neurol 1999; 79: 441 - 456.
Ellerkmann RK, Remy S, Chen J, et al. Molecular and functional changes in voltage - dependent sodium channels following pilocarpine - induced status epilepticus in rat dentate granule cells. Neuroscience 2003; 119: 323 - 333.
Lucas PT, Meadows LS, Nicholls J, et al. An epilepsy mutation in the ? I subunit of the voltage- gated sodium channels results in reduced channel sensitivity to phenytoin. Epilepsy Res 2005; 64: 77 - 84.
Huguenard JR. Low - threshold calcium currents in central nervous system neurons. Annu Rev Physiol 1996; 58: 329 - 348.
Robinson RB, Siegelbaum SA. Hyperpolarization-activated cation currents: from molecules to physiological function. Annu Rev Physiol 2003; 65: 453 - 480.
Loup F, Picard F, Andre VM, et al. Altered expression of ?3 - containing GABA-A receptors in the neocortex of patients with focal epilepsy. Brain 2006; 129: 3277 - 3289.
Rudolph U, Crestani F, Mohler H. GABA-A receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol Sci 2001; 22: 188 - 194.
Brooks - Kayal AR, Shumate MD, Jin H, et al. Selective changes in single cell GABA-A receptor subunit expression and function in temporal lobe epilepsy. Nat Med 1998; 4: 1166 - 1172.
Harty TP, Rogawski MA. Felbamate block of recombinant N-Methyl D-Aspartate receptors: selectivity for the NR2B subunit. Epilepsy Res 2000; 39: 47 - 55.
Dombrowski SM, Desai SY, Marroni M, et al. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 2001; 42: 1501 - 1506.
Dean M, Rzhetsky A, Alikmets R, et al. The human ATP - binding cassette (ABC) transporter superfamily. Genome Res 2001; 11: 1156 - 1166.
Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 1976; 455: 152 - 162.
Loscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 2005; 6: 591 - 602.
Rizzi M, Caccia S, Guiso G, et al. Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmacoresistance. J Neurosci 2002; 22: 5833 - 5839.
Beck H. Plasticity of antiepileptic drug targets. Epilepsia 2007; 48(Suppl. 1): 14 - 18.
Van Vliet EA, Van Schaik R, Edelbroek PM, et al. Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin epileptic rats.
Epilepsia 2006; 47: 672 - 680.
Kunz WS, Kudin AP, Vielhaber S, et al. Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy. Ann Neurol 2000; 48: 766 - 773.
Sleven H, Gibbs JE, Heales S, et al. Depletion of reduced glutathione precedes inactivation of mitochondrial enzymes following limbic status epilepticus in the rat hippocampus. Neurochem Int 2006; 48: 75 - 82.
Verrotti A, Greco R, Altobelli E, et al. Anticardiolipin, glutamic acid decarboxylase and antinuclear antibodies in epileptic patients. Clin Exp Med 2003; 3: 32 - 36.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.