Mechanisms of action for the commonly used antiepileptic drugs: Relevance to antiepileptic drug-associated neurobehavioral adverse effects

Journal of Child Neurology

Volumn 19, Issue SUPPL. 1, 2004, Pages

  Sankar, Raman ^a   Holmes, Gregory L ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR; 4 PHOSPHONOMETHYLPIPECOLIC ACID; 6 NITRO 7 SULFAMOYLBENZO[F]QUINOXALINE 2,3 DIONE; ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; ANTICONVULSIVE AGENT; BARBITURIC ACID DERIVATIVE; BENZODIAZEPINE DERIVATIVE; CALCIUM CHANNEL; CARBAMAZEPINE; CLONAZEPAM; CORTICOSTEROID DERIVATIVE; DIAZEPAM; DIZOCILPINE; ETHOSUXIMIDE; ETIRACETAM; FELBAMATE; FLUMAZENIL; GABAPENTIN; LAMOTRIGINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; PROPOFOL; SCOPOLAMINE; SODIUM CHANNEL; TIAGABINE; TOPIRAMATE; UNINDEXED DRUG; VALPROIC ACID; VIGABATRIN; ZONISAMIDE;

ANTICONVULSANT ACTIVITY; ATTENTION DEFICIT DISORDER; BRAIN TOXICITY; CLINICAL TRIAL; COGNITION; COGNITIVE DEFECT; CONCENTRATION LOSS; DRUG MECHANISM; DRUG POTENTIATION; DRUG RECEPTOR BINDING; EPILEPSY; EPILEPTIC STATE; GABAERGIC TRANSMISSION; HEPATIC ENCEPHALOPATHY; HUMAN; LEARNING DISORDER; MEMORY DISORDER; NEWBORN HYPOXIA; NONHUMAN; PRIORITY JOURNAL; PSYCHOSIS; REVIEW; SEIZURE;

EID: 8344252887     PISSN: 08830738     EISSN: None     Source Type: Journal    
DOI: 10.1177/088307380401900102     Document Type: Review

References (88)

1. Schwartzkroin PA: "Normal" brainmechanisms that support epileptiform activities. Introduction, in Schwartzkroin PA (ed): Epilepsy: Models, Mechanisms, and Concepts. Cambridge, UK, Cambridge University Press, 1993, 358-370.
2. Krall RL, Penry JK, White BG, et al: Antiepileptic drug development. II. Anticonvulsant drug screening. Epilepsia 1978;19:404-428.
3. White HS, Woodhead JH, Wilcox KS, et al: Discovery and preclinical development of antiepileptic drugs, in Levy RH, Mattson RH, Meldrum BS, Perucca E (eds): Antiepileptic Drugs, 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2002, 36-48.
4. Klitgaard H, Matagne A, Lamberty Y: Use of epileptic animals for adverse effect testing. Epilepsy Res 2002;50:55-65.
5. Haugvicova R, Kubova H, Skutova M, Mares P: Anticonvulsant action of topiramate against motor seizures in developing rats. Epilepsia 2000;41:1235-1240.
6. Haugvicova R, Skutova M, Kubova H: Two different anticonvulsant actions of tiagabine in developing rats. Epilepsia 2000;41:1375-1381.
7. Holmes GL, Ben-Ari Y The neurobiology and consequences of epilepsy in the developing brain. Pediatr Res 2001;49:320-325.
8. Sankar R, Shin D, Mazarati AM, et al: Epileptogenesis after status epilepticus reflects age- and model-dependent plasticity. Ann Neurol 2000;48:580-589.
9. Rho JM, Sankar R: The pharmacologic basis of antiepileptic drug action. Epilepsia1999;40:1471-1483.
10. Sankar R, Rho JM: Ontogeny of molecular targets of antiepileptic drugs: Impact on drug choice, in Rho JM, Sankar R, Cavazos JE (eds): Epilepsy: Scientific Foundations of Clinical Practice. New York, Marcel Dekker, 2004, 61-76.
11. Rho JM, Donevan SD, Rogawski MA: Mechanism of action of the anticonvulsant felbamate: Opposing effects on N-methyl-D-aspartate and γ-aminobutyric acid receptors. Ann Neurol 1994; 35:229-234.
12. Gibbs JW III, Sombati S, DeLorenzo RJ, Coulter DA: Cellular actions of topiramate: Blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia 2000;41(Suppl 1):S10-S16.
13. Bliss TV, Collingridge GL: A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 1993;361:31-39.
14. Li HB, Matsumoto K, Tohda M, et al: NMDA-but not AMPA-receptor antagonists augment scopolamine-induced spatial cognitive deficit of rats in a radial maze task. Brain Res 1996;725:268-271.
15. Pitsikas N, Rigamonti AE, Cella SG, Muller EE: The non-NMDA receptor antagonist NBQX does not affect rats performance in the object recognition task. Pharmacol Res 2002;45:43-46.
16. Coulter DA, Huguenard JR, Prince DA: Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons. Ann Neurol 1989;25:582-593.
17. Kelly KM, Gross RA, Macdonald RL: Valproic acid selectively reduces the low-threshold (T) calcium current in rat nodose neurons. Neurosci Lett 1990;116:233-238.
18. Suzuki S, Kawakami K, Nishimura S, et al: Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res 1992;12:21-27.
19. Snead OC: Basic mechanisms of generalized absence seizures. Ann Neurol 1995;37:146-157.
20. Poolos NP: The yin and yang of the H-channel and its role in epilepsy. Epilepsy Curr 2004;4:3-6.
21. Poolos NP, Mighore M, Johnston D: Pharmacological upregulation of H-channels reduces the excitability of pyramidal neuron dendrites. Nat Neurosci 2002;5:767-774.
22. h in rat CA1 pyramidal cells. Epilepsia 2003;44:150-156.
23. Gooday R, Hayes PC, Bzeizi K, O'Carroll RE: Benzodiazepine receptor antagonism improves reaction time in latent hepatic encephalopathy. Psychopharmacology (Berl) 1995; 119:295-298.
24. Smythe JW, Murphy D, Costall B: Benzodiazepine receptor stimulation blocks scopolamine-induced learning impairments in a water maze task. Brain Res Bull 1996;41:299-304.
25. Gee NS, Brown JP, Dissanayake VU, et al: The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem 1996;271:5768-5776.
26. +-evoked [3H]-norepinephrine release from rat neocortical slices. Synapse 2002;45:171-190.
27. Zhang X, Velumian AA, Jones OT, Carlen PL: Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia 2000;41(Suppl 1):S52-S60.
28. Angehagen M, Ben-Menachem E, Shank R, et al: Topiramate modulation of kainate-induced calcium currents is inversely related to channel phosphorylation level. J Neurochem 2004;88:320-325.
29. Lukyanetz EA, Shkryl VM, Kostyuk PG: Selective blockade of N-type calcium channels by levetiracetam. Epilepsia 2002;43:9-18.
30. Stefam A, Pisard A, De Murtas M, et al: Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents. Epilepsia 1995;36:997-1002.
31. Sutula T, Cavazos J, Golarai G: Alteration of long-lasting structural and functional effects of kamic acid in the hippocampus by brief treatment with phenobarbital. J Neurosci 1992; 12:4173-4187.
32. Amano K, Hamada K, Yagi K, Seino M: Antiepileptic effects of topiramate on amygdaloid kindling in rats. Epilepsy Res 1998; 31:123-128.
33. Stratton SC, Large CH, Cox B, et al: Effects of lamotrigine and levetiracetam on seizure development in a rat amygdala kindling model. Epilepsy Res 2003;53:95-106.
34. Hamada K, Song HK, Ishida S, et al: Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling in rats. Epilepsia 2001;42:1379-1386.
35. Löscher W, Honack D, Rundfeldt C: Antiepileptogenic effects of the novel anticonvulsant levetiracetam (ucb L059) in the kindling model of temporal lobe epilepsy. J Pharmacol Exp Ther 1998; 284:474-479.
36. Tauck DL, Nadler JV: Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. J Neurosci 1985;5:1016-1022.
37. Sutula T, Cascino G, Cavazos J, et al: Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol 1989;26:321-330.
38. Mello LE, Cavalheiro, EA, Tan AM, et al: Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: Cell loss and mossy fiber sprouting. Epilepsia 1993;34:985-995.
39. Nadler JV. The recurrent mossy fiber pathway of the epileptic brain. Neurochem Res 2003;28:1649-1658.
40. Coulter DA: Mossy fiber zinc and temporal lobe epilepsy: Pathological association with altered "epileptic" gamma-aminobutyric acid A receptors in dentate granule cells. Epilepsia 2000;41(Suppl 6):S96-S99.
41. Rigo JM, Hans G, Nguyen L, et al: The anti-epileptic drug levetiracetam. reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents. Br J Pharmacol 2002;136:659-672.
42. Mshman RH, Yanai J: Long-lasting effects of early barbiturates on central nervous system and behavior. Neurosci Biobehav Rev 1983;7:19-28.
43. Diaz J, Schain RJ, Bailey BG: Phenobarbital-induced brain growth retardation in artificially reared rat pups. Biol Neonate 1977;32:77-82.
44. Yanai J, Rosselli-Austin L, Tabakoff B: Neuronal deficits in mice following prenatal exposure to phenobarbital. Exp Neurol 1979;64:237-244.
45. Serrano EE, Kunis DM, Ransom BR: Effects of chronic phenobarbital exposure on cultured mouse spinal cord neurons. Ann Neurol 1988;24:429-438.
46. Bergey GK, Swaiman KF, Schher BK, et al: Adverse effects of phenobarbital on morphological and biochemical development of fetal mouse spinal cord neurons in culture. Ann Neurol 1981;9:584-589.
47. Mikati MA, Holmes GL, Chronopoulos, A et al: Phenobarbital modifies seizure-related brain injury in the developing brain. Ann Neurol 1994-136:425-433.
48. File SE, Wilks LJ: Changes in seizure threshold and aggression during chronic treatment with three anticonvulsants and on drug withdrawal. Psychopharmacology (Berl) 1990;100:237-242.
49. Diaz J, Schain RJ: Phenobarbital: Effects of long-term administration on behavior and brain of artificially reared rats. Science 1978;199:90-91.
50. Yanai J, Fares F, Gavish M, et al: Neural and behavioral alterations after early exposure to phenobarbital. Neurotoxicology 1989; 10:543-554.
51. Picker M, Thomas J, Koch C, Poling A: Effects of phenytoin, phenobarbital, and valproic acid, alone and in selected combinations, on schedule-controlled behavior of rats. Pharmacol Biochem Behav 1985;22:389-393.
52. Krafft K, Lyon DO, Poling A: Effects of phenytoin on schedule-controlled performance of rats. Psychopharmacology (Berl) 1982; 78:93-95.
53. Renfrey G, Schlinger H, Jakubow J, Poling A: Effects of phenytoin and phenobarbital on schedule-controlled responding and seizure activity in the amygdala-kindled rat. J Pharmacol Exp Ther 1989;248:967-973.
54. Sankar R, Shin DH, Liu H, et al: Patterns of status epilepticus-induced neuronal injury during development and long-term consequences. J Neurosci 1998;18:8382-8393.
55. Rostock A, Hoffmann W, Siegemund C, Bartsch R: Effects of carbamazepine, valproate calcium, clonazepam and piracetam. on behavioral test methods for evaluation of memory-enhancing drugs. Methods Find Exp Clin Pharmacol1989;11:547-553.
56. Smith DF: Lithium and carbamazepine: Effects on learned taste aversion and open field behavior in rats. Pharmacol Biochem Behav 1983;18:483-488.
57. Bolanos AR, Sarkisian M, Yang Y, et al: Comparison of valproate and phenobarbital treatment after status epilepticus in rats. Neurology 1998;51:41-48.
58. Voigt JP, Morgenstern E, Fink H: Memory-enhancing effects of benzodiazepines in mice. Eur Neuropsychopharmacol 1996;6:253-255.
59. Pereira ME, Rosat R, Huang CH, et al: Inhibition by diazepam of the effect of additional training and of extinction on the retention of shuttle avoidance behavior in rats. Behav Neurosci 1989;103:202-205.
60. Holley LA, Turchi J, Apple C, Sarter M: Dissociation between the attentional effects of infusions of a benzodiazepine receptor agonist and an inverse agonist into the basal forebrain. Psychopharmacology (Berl) 1995;120:99-108.
61. Bittigau P, Sifringer M, Genz K, et al: Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A 2002;99:15089-15094.
62. Jevtwic-Todorovic V, Hartman RE, Izumi Y, et al: Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003;23:876-882.
63. Petroff OA, Rothman DL, Behar KL, et al. The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Ann Neurol 1996;39:95-99.
64. Bryans JS, Davies N, Gee NS, et al: Identification of novel ligands for the gabapentin binding site on the α2δ subunit of a calcium channel and their evaluation as anticonvulsant agents. J Med Chem 1998;4:1838-1845.
65. Acosta GB, Boccia MM, Baratti CM: Gabapentin, an antiepileptic drug, improves memory storage in mice. Neurosci Lett 2000;279:173-176.
66. Boccia MM, Acosta GB, Baratti CM: Memory improving actions of gabapentin in mice: Possible involvement of central muscarinic cholinergic mechanism. Neurosci Lett 2001;311:153-156.
67. Cilio MR, Bolanos AR, Liu Z, et al: Anticonvulsant action and long-term effects of gabapentin in the immature brain. Neuropharmacology 2001;40:139-147.
68. Coenen AM, Blezer EH, van Luijtelaar EL: Effects of the GABA-uptake inhibitor tiagabine on electroencephalogram, spike-wave discharges and behaviour of rats. Epilepsy Res 1995;21:89-94.
69. Schmitt U, Hiemke C: Tiagabine, a gamma-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze. Behav Brain Res 2002; 133:391-394.
70. Bryant RC, Petty F, Byrne WL: Effects of piracetam (SKF 38462) on acquisition, retention, and activity in the goldfish. Psychopharmacologia 1973;29:121-130.
71. Wolthuis OL: Behavioural effects of etiracetam in rats. Pharmacol Biochem Behav 1981;15:247-255.
72. Verloes R, Scotto AM, Gobert J, Wülfert E: Effects of nootropic drugs in a scopolamine-induced amnesia model in mice. Psychopharmacology. 1988;95:226-230.
73. Lamberty Y, Margineanu DG, Klitgaard H: Absence of negative impact of levetiracetam on cognitive function and memory in normal and amygdala-kindled rats. Epilepsy Behav 2000;1:333-342.
74. Klitgaard H, Matagne A, Gobert J, Wülfert E: Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. Eur J Pharmacol 1998;353:191-206.
75. Cha BH, Silveira DC, Liu X, et al: Effect of topiramate following recurrent and prolonged seizures during early development. Epilepsy Res 2002;51:217-232.
76. Pohl D, Bittigau P, Ishimaru MJ, et al: N-Methyl-D-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain. Proc Natl Acad Sci U S A 1999;96:2508-2513.
77. Ikonomidou C, Bosch F, Miksa M, et al: Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999;283:70-74.
78. Koh S, Jensen FE: Topiramate blocks perinatal hypoxia-induced seizures in rat pups. Ann Neurol 2001;50:366-372.
79. Jensen FE, Blume H, Alvarado S, et al: NBQX blocks acute and late epileptogenic effects of perinatal hypoxia. Epilepsia 1995;36:966-972.
80. Tatum WO IV, French JA, Faught E, et al for the PADS Investigators: Postmarketing experience with topiramate and cognition. Epilepsia 2001;42:1134-1140.
81. Gerber PE, Hamiwka L, Connolly MB, Farrell K: Factors associated with behavioral and cognitive abnormalities in children receiving topiramate. Pediatr Neurol 2000;22:200-203.
82. Aldenkamp AP, Baker G, Mulder OG, et al: A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Epilepsia 2000;41:1167-1178.
83. Thompson PJ, Baxendale SA, Duncan JS, Sander JW: Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatry 2000;69:636-641.
84. Kanner AM, Wuu J, Faught E, et al and the PADS Investigators: A past psychiatric history may be a risk factor for topiramate-related psychiatric and cognitive adverse events. Epilepsy Behav 2003;4:548-552.
85. Mula M, Trimble MR, Lhatoo SD, Sander JW: Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia 2003;44:659-663.
86. Mula M, Trimble MR, Thompson P, Sander JW: Topiramate and word-finding difficulties in patients with epilepsy. Neurology 2003;60:1104-1107.
87. Mula M, Trimble MR, Yuen A, et al: Psychiatric adverse events during levetiracetam therapy. Neurology 2003;61:704-706.
88. Hori M, Ito T, Oka M, et al: General pharmacology of the novel antiepileptic compound zonisamide. First communication: Effects on central nervous system. Arzneimittelforschung 1987;37: 1124-1130.