Antiepileptic drugs and the developing brain

Cellular and Molecular Life Sciences

Volumn 63, Issue 4, 2006, Pages 399-413

  Kaindl, A M ^a,b   Asimiadou, S ^a   Manthey, D ^a   Hagen, M V D ^b   Turski, L ^c   Ikonomidou, C ^b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^c Solvay Pharmaceuticals Inc   (Netherlands)

Author keywords

Antiepileptic drugs; Apoptosis; Development; Neurodegeneration; Synaptogenesis

Indexed keywords

ANESTHETIC AGENT; ANTICONVULSIVE AGENT; BARBITURIC ACID DERIVATIVE; BENZODIAZEPINE; CARBAMAZEPINE; CLONAZEPAM; CORTICOTROPIN; DIAZEPAM; ETHOSUXIMIDE; ETIRACETAM; FELBAMATE; GABAPENTIN; KETAMINE; LAMOTRIGINE; MIDAZOLAM; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NITROUS OXIDE; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; PIRACETAM; SCOPOLAMINE; SEDATIVE AGENT; SULTIAME; TIAGABINE; TOPIRAMATE; UNINDEXED DRUG; VALPROIC ACID; VIGABATRIN; ZONISAMIDE;

APOPTOSIS; BEHAVIOR; BRAIN DEVELOPMENT; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CLEFT LIP FACE PALATE; COGNITION; COGNITIVE DEFECT; DRUG MECHANISM; EMBRYOTOXICITY; EPILEPSY; FACE DEFORMITY; FETAL HYDANTOIN SYNDROME; FETUS MALFORMATION; FINGER MALFORMATION; GROWTH RETARDATION; HUMAN; LANGUAGE DISABILITY; LEARNING DISORDER; MENTAL DEFICIENCY; MICROCEPHALY; MYELINATION; NERVE CELL PLASTICITY; NERVE FIBER; NEURAL TUBE DEFECT; NEUROTOXICITY; NONHUMAN; REVIEW; SPINA BIFIDA; SYNAPTOGENESIS; TERATOGENICITY;

ANIMALS; ANTICONVULSANTS; APOPTOSIS; BRAIN; EPILEPSY; HUMANS; NEURONS;

ANIMALIA; MAMMALIA;

EID: 33645068437     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-005-5348-0     Document Type: Review

References (201)

1. Hauser W. A. (1994) The prevalence and incidence of convulsive disorders in children. Epilepsia 35: Suppl. 2: S1-S6
2. Rogawski M. A. and Löscher W. (2004) The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat. Med. 10: 685-692
3. Brodie M. J. and Dichter M. A. (1996) New antiepileptic drugs. N. Engl. J. Med. 334: 168-175
4. Sankar R. (2004) Initial treatment of epilepsy with antiepileptic drugs. Neurology 63: S30-S39
5. Rogawski M. A. and Löscher W. (2004) The neurobiology of antiepileptic drugs. Nat. Rev. Neurosci. 5: 553-564
6. Olney J. W., Jevtovic-Todorovic V. and Ikonomidou C. (2004) Do pediatric drugs cause developing neurons to commit suicide? Trends Pharmacol. Sci. 25: 135-139
7. Tatulian L., Delmas P., Abogadie F. C. and Brown D. A. (2001) Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J. Neurosci. 21: 5535-5545
8. Leach M. J., Marden C. M. and Miller A. A. (1986) Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia 27: 490-497
9. Prakriya M. and Mennerick S. (2000) Selective depression of low-release probability excitatory synapses by sodium channel blockers. Neuron 26: 671-682
10. Brown J. P. and Gee N. S. (1998) Cloning and deletion mutagenesis of the alpha2 delta calcium channel subunit from porcine cerebral cortex. Expression of a soluble form of the protein that retains [3H]gabapentin binding activity. J. Biol. Chem. 273: 25458-25465
11. 2δ subunits - structure and gabapentin binding. Mol. Pharmacol 59: 1243-1248
12. 2δ subunit of a calcium channel and their evaluation as anticonvulsant agents. J. Med. Chem. 4: 1838-1845
13. - current. J. Neurosci. 13: 3211-3221
14. 2+ currents in cortical neurons: functional implications. Eur. J. Pharmacol. 307: 113-116
15. Wang S.-J., Huang C.-C., Hsu K.-S., Tsai J.-J. and Gean P.-W. (1996) Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones. Neuroreport 7: 3037-3040
16. 2+ currents. Seizure 10: 279-286
17. 2+ current in pyramidal neurones of rat hippocampal slices. Neurosci. Lett. 306: 5-8
18. Lukyanetz E. A., Shkryl V. M. and Kostyuk P. G. (2002) Selective blockade of N-type calcium channels by levetiracetam. Epilepsia 43: 9-18
19. 2+ channel currents in cultured sensory neurones is dependent on culture conditions and channel subunit expression. Neuropharmacology 42: 353-366
20. Sutton K. G., Martin D. J., Pinnock R. D., Lee K. and Scott R. H. (2002) Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Brit. J. Pharmacol. 135: 257-265
21. Sarantopoulos C., McCallum B., Kwok W. M. and Hogan Q. (2002) Gabapentin decreases membrane calcium currents in injured as well as in control mammalian primary afferent neurons. Reg. Anesth. Pain. Med. 27: 47-57
22. +-evoked glutamate release from rat neocortical and hippocampal slices by gabapentin. Neurosci. Lett. 280: 107-110
23. Shimoyama M., Shimoyama N. and Hori Y. (2000) Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn. Pain 85: 405-414
24. Perez-Reyes E. (2003) Molecular physiology of low-voltage-activated T-type calcium channels. Physiol. Rev. 83: 117-161
25. Huguenard J. R. (1996) Low-threshold calcium currents in central nervous system neurons. Annu. Rev. Physiol. 58: 329-358
26. Suzuki S. and Rogawski M. A. (1989) T-type calcium channels mediate the transition between tonic and phasic firing in thalamic neurons. Proc. Natl Acad. Sci. USA 86: 7228-7232
27. Coulter D. A., Huguenard J. R. and Prince D. A. (1989) Characterization of ethosuximide reduction of low-threshold calcium current in thalamic relay neurons. Ann. Neurol. 25: 582-593
28. Sankar R. and Holmes GL. (2004) Mechanisms of action for the commonly used antiepileptic drugs: relevance to anti-epileptic drug-associated neurobehavioral adverse effects. J. Child Neurol. 19: Suppl. 1: S6-14
29. Miles R. and Wong R. K. (1987) Inhibitory control of local excitatory circuits in the guinea-pig hippocampus. J. Physiol. (Lond.) 388: 611-629
30. γ2- subunit in childhood absence epilepsy and febrile seizures. Nat. Genet. 28: 49-52
31. A receptor dysfunction in epilepsy: a mutation in the γ2-subunit gene. Nat. Genet. 28: 46-48
32. Kananura C., Haug K., Sander T., Runge U., Gu W., Hallmann K. et al. (2002) A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions. Arch. Neurol. 59: 1137-1141
33. A-receptor γ2 subunit in a family with generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet. 70: 530-536
34. Cossette P., Liu L., Brisebois K., Dong H., Lortie A., Vanasse M. et al. (2001) Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat. Genet. 31: 184-189
35. A receptor subtypes. Nature 401: 796-800
36. Crestani F., Martin J. R., Möhler H. and Rudolph U. (2000) Mechanism of action of the hypnotic zolpidem in vivo. Br. J. Pharmacol. 131: 1251-1256
37. A receptors in hippocampal neurons. Mol. Pharmacol. 59: 814-824
38. A receptor channels. Annu. Rev. Neurosci. 17: 569-602
39. Rho J. M., Donevan S. D. and Rogawski M. A. (1997) Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate. J. Pharmacol. Exp. Ther. 280: 1383-1391
40. White H. S., Brown S. D., Woodhead J. H., Skeen G. A. and Wolf H. H. (1997) Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res. 28: 167-179
41. A receptors expressed in Xenopus oocytes to modulation by topiramate. Epilepsia 41: S25-S29
42. De Biase D., Barra D., Bossa F., Pucci P. and John R. A. (1991) Chemistry of the inactivation of 4-aminobutyrate aminotransferase by the antiepileptic drug vigabatrin. J. Biol. Chem. 266: 20056-20061
43. Löscher W. and Horstermann D. (1994) Differential effects of vigabatrin, γ-acetylenic GABA, aminooxyacetic acid and valproate on levels of various amino acids in rat brain regions and plasma. Naunyn Schmiedeberg's Arch. Pharmacol. 349: 270-278
44. Jackson M. F., Esplin B. and Čapek, R. (2000) Reversal of the activity-dependent suppression of GABA-mediated inhibition in hippocampal slices from γ-vinyl GABA (vigabatrin)-pretreated rats. Neuropharmacology 39: 65-74
45. Kang J. and Macdonald R. L. (2004) The GABAA receptor gamma2 subunit R43Q mutation linked to childhood absence epilepsy and febrile seizures causes retention of alpha1beta2-gamma2S receptors in the endoplasmic reticulum. J. Neurosci. 24: 8672-8677
46. Naylor D. E., Liu H. and Wasterlain C. G. (2005) Trafficking of GABAA receptors, loss of inhibition and a mechanism for pharmacoresistance in status epilepticus. J. Neurosci. 25: 7724-7733
47. Suzdak P. D. and Jansen J. A. (1995) A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor. Epilepsia 36: 612-626
48. Thompson S. M. and Gahwiler B. H. (1992) Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. J. Neurophysiol. 67: 1698-1701
49. Engel D., Schmitz D., Gloveli T., Frahm C., Heinemann U. and Draguhn A. (1998) Laminar difference in GABA uptake and GAT-1 expression in rat CA1. J. Physiol. (Lond.) 512: 643-649
50. Jackson M. F., Esplin B. and Čapek, R. (1999) Activity-dependent enhancement of hyperpolarizing and depolarizing γ-aminobutyric acid (GABA) synaptic responses following inhibition of GABA uptake by tiagabine. Epilepsy Res. 37: 25-36
51. Dingledine R., Borges K., Bowie D. and Traynelis S. F. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51: 7-61
52. Rogawski M. A., Gryder D., Castaneda D., Yonekawa W., Banks M. K. and Lia H. (2003) GluR5 kainate receptors, seizures and the amygdala. Ann. N. Y. Acad. Sci. 985: 150-162
53. Subramaniam S., Rho J. M., Penix L., Donevan S. D., Fiedling R. P. and Rogawski M. A. (1995) Felbamate block of the N-methyl-D-aspartate receptor. J. Pharmacol. Exp. Ther. 273: 878-886
54. Kuo C. C., Lin B. J., Chang H. R. and Hsieh C. P. (2004) Use-dependent inhibition of the N-methyl-D-aspartate currents by felbamate: a gating modifier with selective binding to the desensitized channels. Mol. Pharmacol. 65: 370-380
55. Kleckner N. W., Glazewski J. C., Chen C. C. and Moscrip T. D. (1999) Subtype-selective antagonism at N-methyl-D-aspartate receptors by felbamate: insights into the mechanism of action. J. Pharmacol. Exp. Ther. 289: 886-894
56. Harty T. P. and Rogawski M. A. (2000) Felbamate block of recombinant N-methyl-D-aspartate receptors: selectivity for the NR2B subunit. Epilepsy Res. 39: 47-55
57. Meldrum B. S. (1996) Excitatory amino acid receptors and their role in epilepsy and cerebral ischemia. Ann. N. Y. Acad. Sci. 757: 492-505
58. Lerma J., Paternain A. V., Rodriguez-Moreno A. and López-Garcia J. C. (2001) Molecularphysiology of kainate receptors. Physiol. Rev. 81: 971-998
59. Gryder D. S. and Rogawski M. A. (2003) Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons. J. Neurosci. 23: 7069-7074
60. Kamiski R. M., Banerjee M. and Rogawski M. A. (2004) Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology 46: 1097-1104
61. Rodier P. M. (1980) Chronology of neuron development: animal studies and their clinical implications. Dev. Med. Child Neurol. 22: 525-545
62. Rodier P. M. (1994) Vulnerable periods and processes during central nervous system development. Environ. Health Perspect. 102 (Suppl. 2): 121-124
63. Dobbing J. and Sands J. (1993) The quantitative growth and development of the human brain. Arch. Dis. Child. 48: 757-767
64. Dobbing J. (1974) The later development of the brain and its vulnerability. In: Scientific Foundations of Pediatrics, pp. 565-577, Davis J. A. and Dobbing J. (eds.), Saunders, Philadelphia
65. Smart J. L. (1991) Critical periods in brain development. In: The Childhood Environment and Adult Disease (Ciba Found. Symp. 156), pp. 109-128, Wiley, Winchester, PA
66. Bayer S. A., Altman J., Russo R. J. and Zhang X. (1993) Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology 14: 83-144
67. Passingham R. E. (1985) Rates of brain development in mammals including man. Brain Behav. Evol. 26: 167-175
68. Rodier P. M. (1995) Developing brain as a target of toxicity. Environ. Health Perspect. 103 (Suppl. 6): 73-76
69. Emerit M. B., Riad M. and Hamon M. (1992) Trophic effects of neurotransmitters during brain maturation. Biol. Neonate 62: 193-201
70. Retz W., Kornhuber J. and Riederer P. (1996) Neurotransmission and the ontogeny of human brain. J. Neural Transm. 103: 403-419
71. Levitt P., Harvey J. A., Friedman E., Simansky B. and Murphy E. H. (1997) New evidence for neurotransmitter influences on brain development. Trends Neurosci. 20: 269-274
72. Nguyen L., Rigo J. M., Rocher V., Belachew S., Malgrange B., Rogister B. et al. (2001) Neurotransmitters as early signals for central nervous system development. Cell Tissue Res. 305: 187-202
73. Johnson E. M. and Deckwerth T. L. (1993) Molecular mechanisms of developmental neuronal death. Annu. Rev. Neurosci. 16: 31-46
74. Henderson C. E. (1996) Programmed cell death in the developing nervous system. Neuron 17: 579-585
75. Ikonomidou C., Bittigau P., Koch C., Genz K., Hoester F., Felderhoff-Mueser U. et al. (2001) Neurotransmitters and apoptosis in the developing brain. Biochem. Pharmacol. 62: 401-405
76. Ikonomidou C., Bosch F., Miksa M., Bittigau P., Vöckler J., Dikranian K. et al. (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283: 70-74
77. Ikonomidou C., Bittigau P., Ishimaru M. J., Koch C., Genz K., Price M. T. et al. (2000) Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287: 1056-1060
78. Webb S. J., Monk C. S. and Nelson C. A. (2001) Mechanisms of postnatal neurobiological development: implications for human development. Dev. Neurophychol. 19: 147-171
79. Speidel B. D. and Meadow S. R. (1972) Maternal epilepsy and abnormalities of the fetus and newborn. Lancet 308: 839-843
80. Strickler S. M., Dansky L. V., Miller M. A., Seni M. H., Andermann E. and Spielberg S. P. (1985) Genetic predisposition to phenytoin-induced birth defects. Lancet 2: 746-749
81. Jones K. L., Lacro R. V., Johnson K. A. and Adams J. (1989) Pattern of malformations in the children of women treated with carbamazepine during pregnancy. N. Engl. J. Med. 320: 1661-1666
82. Buehler B. A., Delimont D., van Waes M. and Finnell R. H. (1990) Prenatal prediction of risk of the fetal hydantoin syndrome. N. Engl. J. Med. 322: 1567-1572
83. Holmes L. B., Harvey E. A., Coull B. A., Huntington K. B., Khoshbin S., Hayes A. M. et al. (2001) The teratogenicity of anticonvulsant drugs. N. Engl. J. Med. 344: 1132-1138
84. Zahn C. A. (1998) Neurologic care of pregnant women with epilepsy. Epilepsia 39 (Suppl. 8): S26-S31
85. Zigler E., Balla D. and Hodapp R. M. (1984) On the definition and classification of mental retardation. Am. J. Ment. Defic. 89: 215-230
86. Willerman L. and Fedler M. F. (1977) Intellectually precocious preschool children: early development and later intellectual accomplishments. J. Genet. Psychol. 131: 13-20
87. Van der Pol M. C., Hadders-Algra M., Huisies H. J. and Touwen B. C. (1991) Antiepileptic medication in pregnancy: late effects on the children's central nervous system development. Am. J. Obstet. Gynecol. 164: 121-128
88. Reinisch J. M., Sanders S. A., Mortensen E. L. and Rubin D. B. (1995) In utero exposure to phenobarbital and intelligence deficits in adult men. JAMA 274: 1518-1525
89. Winter R. M., Donnai D., Burn J. and Tucker S. M. (1997) Fetal valproate syndrome: is there a recognizable phenotype? J. Med. Genet. 24: 692-695
90. Wyszynski D. F., Nambisan M., Surve T., Alsdorf R. M., Smith C. R., Holmes L. B. (2005) Antiepileptic drug pregnancy registry. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 64: 961-965
91. Lindhout D. and Schmidt D. (1986) In utero exposure to valproate and neural tube defects. Lancet 1: 1392-1393
92. Rosa F. W. (1991) Spina bifida in infants of women treated with carbamazepine during pregnancy. N. Engl. J. Med. 324: 674-677
93. Matalon S., Schechtman S., Goldzweig G. and Ornoy A. (2002) The teratogenic effect of carbamazepine: a meta-analysis of 1255 exposures. Reprod. Toxicol. 16: 9-10
94. Hanson J. W. (1976) Fetal hydanthoin syndrome. Teratology 13: 185-188
95. Hansen D. K. (1991) The embryotoxicity of phenytoin: a review of possible mechanisms. Proc. Soc. Exp. Biol. Med. 197: 361-368
96. Finnell R. H. and Chernoff G. F. (1984) Variable patterns of malformation in the mouse fetal hydanthoin syndrome. Am. J. Med. Genet. 19: 463-471
97. Adams J., Vorhees C. V. and Middaugh L. D. (1990) Developmental neurotoxicity of anticonvulsants: human and animal evidence on phenytoin. Neurotoxicol. Teratol. 12: 203-214
98. Van Overloop D., Schnell R. R., Harvey E. A. and Holmes L. B. (1992) The effects of prenatal exposure to phenytoin and other anticonvulsants on intellectual function at 4 to 8 years of age. Neurotoxicol. Teratol. 14: 329-335
99. Dessens A. B., Cohen-Kettenis P. T., Mellanbergh G. F., Koppe J. G., van de Poll N. E. et al. (2000) Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems. Acta Paediatr. 89: 533-541
100. Rovet J., Cole S. and Nulman I. (1995) Effects of maternal epilepsy on children's neurodevelopment. Child Neuropsychol. 1: 150-157
101. Adab N., Jacoby A., Smith D. and Chadwick D. (2001) Additional educational needs in children born to mothers with epilepsy. J Neurol. Neurosurg. Psychiatry 70: 15-21
102. Mawer G., Clayton-Smith J., Coyle H. and Kini U. (2002) Outcome of pregnancy in women attending an outpatient epilepsy clinic: adverse features associated with higher doses of sodium valproate. Seizure 1: 512-518
103. Gaily E., Kantola-Sorsa E. and Granstrom M. L. (1988) Intelligence of children of epileptic mothers. J. Pediatr. 113: 677-684
104. Gaily E., Kantola-Sorsa E. and Granstrom M. L. Specific cognitive dysfunction in children with epileptic mothers. Dev. Med. Child Neurol. 32: 403-414
105. Hanson J. W., Myrianthopoulos N. C., Harvey M. A. and Smith D. W. (1976) Risks to the offspring of women treated with hydantoin anticonvulsants, with emphasis on the fetal hydantoin syndrome. J. Pediatr. 89: 662-668
106. Koch S., Titze K. and Zimmermann R. B. (1999) Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents. Epilepsia 40: 1237-1243
107. Scolnick D., Nulman I. and Rovet J. (1994) Neurodevelopment of children exposed in utero to phenytoin and carbamazepine monotherapy. JAMA 271: 767-770
108. Leavitt M. D., Yerby M. S., Robinson N., Sells C. J. and Erickson D. M. (1982) Epilepsy in pregnancy: developmental outcome of offspring at 12 months. Neurology 42: 141-143
109. Losche G., Steinhausen H. C., Koch S. and Helge H. (1994) The psychological development of children of epileptic parent. The differential impact of intrauterine exposure to anticonvulsant drugs and further influential factors. Acta Paediatr. 83: 961-966
110. Adab N., Kini U., Vinten J., Ayres J., Baker G., Clayton-Smith J. et al. (2004) The long term outcome of children born to mothers with epilepsy. J. Neurol. Neurosurg. Psychiatry 75: 1575-1583
111. Ornoy A. and Cohen E. (1996) Outcome of children born to epileptic mothers treated with carbamazepine during pregnancy. Arch. Dis. Child. 75: 517-520
112. Moore S. J., Turnpenny P., Quinn A., Glover S., Lloyd A. J., Montgomery T. et al. (2000) A clinical study of 57 children with fetal anticonvulsant syndromes. J. Med. Genet. 37: 489-497
113. Kozma C. (2001) Valproic acid embryopathy: report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature. Am. J. Med. Genet. 98: 168-175
114. Vinten J., Adab N., Kini U., Gorry J., Gregg J. and Baker G. A., for the Liverpool and Manchester Neurodevelopment Study Group* (2005) Neuropsychological effects of exposure to anticonvulsant medication in utero. Neurology 64: 949-954
115. Farwell J. R., Lee Y. J., Hirtz D. G., Sulzbacher S. I., Ellenberg J. H. and Nelson K. B. (1990) Phenobarbital for febrile seizures - effects on intelligence and on seizure recurrence. N. Engl. J. Med. 322: 364-369
116. Sulzbacher S., Farwell J. R., Temkin N., Lu A. S. and Hirtz D. G. (1999) Late cognitive effects of early treatment with phenobarbital. Clin. Pediatr. Phila. 38: 387-394
117. Thorp J. A., O'Connor M., Jones A. M., Hoffman, E. L. and Belden B. (1999) Does perinatal phenobarbital exposure affect developmental outcome at age 2? Am. J. Perinatol. 16: 51-60
118. Fishman R. H. and Yanai J. (1983) Long-lasting effects of early barbiturates on central nervous system and behavior. Neurosci. Biobehav. Rev. 7: 19-28
119. Diaz J., Schain R. J. and Bailey B. G. (1977) Phenobarbital-induced brain growth retardation in artificially reared rat pups. Biol. Neonate 32: 77-82
120. Yanai J., Rosselli-Austin L. and Tabakoff B. (1979) Neuronal deficits in mice following prenatal exposure to phenobarbital. Exp. Neurol. 64: 237-244
121. Schain R. J. and Watanabe K. (1975) Effect of chronic phenobarbital administration upon brain growth in the infant rat. Exp. Neurol. 49: 509-515
122. Fishman R. H. B., Ornoy A., Yanai J. (1983) Ultrastructural evidence of long-lasting cerebellar degeneration after early exposure to phenobarbital in mice. Exp. Neurol. 79: 212-222
123. Bergman A., Feigenbaum J. J. and Yanai J. (1982) Neuronal losses in mice following both prenatal and neonatal exposure to phenobarbital. Acta Anat. 114: 185-192
124. Roger-Fuchs Y., Newman M. E., Trombka D., Zabalke E. and Yanai J. (1992) Hippocampal cholinergic alterations and related behavioral deficits after early exposure to phenobarbital. Brain Res. Bull. 29: 1-6
125. Diaz J. and Schain R. J. (1978) Phenobarbital: effects of long-term administration on behavior and brain of artificially reared rats. Science 199: 90-91
126. Yanai J., Fares F., Gavish M., Greenfeld Z., Katz Y., Marcovici G. et al. (1989) Neural and behavioral alterations after early exposure to phenobarbital. Neurotoxicology 10: 543-554
127. Pick C. G. and Yanai J. (1985) Long-term reduction in eight arm maze performance after early exposure to phenobarbital. Int. J. Dev. Neurosci. 3: 223-227
128. Mikati M. A., Holmes G. L., Chronopoulos A., Hyde P., Thurber S., Gatt A. et al. (1994) Phenobarbital modifies seizure-related brain injury in the developing brain. Ann Neurol. 36: 425-433
129. File S. E. and Wilks L. J. (1990) Changes in seizure threshold and aggression during chronic treatment with three anticonvulsants and on drug withdrawal. Psychopharmacology (Berl.) 100: 237-242
130. Picker M., Thomas J., Koch C. and Poling A (1985) Effects of phenytoin, phenobarbital, and valproic acid, alone and in selected combinations, on schedule-controlled behavior of rats. Pharmacol. Biochem. Behav. 22: 389-393
131. Krafft K., Lyon D. O. and Poling A. (1982) Effects of phenytoin on schedule-controlled performance of rats. Psychopharmacology (Berl.) 78: 93-95
132. Renfrey G., Schlinger H., Jakubow J. and Poling A. (1989) Effects of phenytoin and phenobarbital on schedule-controlled responding and seizure activity in the amygdala-kindled rat. J. Pharmacol. Exp. Ther. 248: 967-973
133. Rostock A., Hoffmann W., Siegemund C. and Bartsch R. (1989) effects of carbamazepine, valproate calcium, clonazepam and piracetam on behavioral test methods for evaluation of memory-enhancing drugs. Methods Find. Exp. Clin. Pharmacol. 11: 547-553
134. Smith D. F. (1983) Lithium and carbamazepine: effects on learned taste aversion and open field behavior in rats. Pharmacol. Biochem. Behav. 18: 483-488
135. Hatta T., Ohmori H., Murakami T., Takano M., Yamashita K. and Yasuda M. (1999) Neurotoxic effects of phenytoin on postnatal mouse brain development following neonatal administration. Neurotoxicol. Teratol. 21: 21-28
136. Vorhees C. V. (1987) Fetal hydanthoin syndrome in rats: dose-effect relationships of prenatal phenytoin on postnatal development and behavior. Teratology 35: 287-303
137. Vorhees C. V. and Minck D. R. (1989) Long-term effects of prenatal phenytoin exposure on offspring behavior in rats. Neurotoxicol. Teratol. 11: 295-305
138. Schilling M. A., Inman S. L., Morford L. L., Moran M. S., Vorhees C. V. (1999) Prenatal phenytoin exposure and spatial navigation in offspring: effects on reference and working memory and on discrimination learning. Neurotoxicol. Teratol. 21: 567-578
139. Vorhees C. V., Acuff K. D., Weisenburger W. P. and Minck D. R. (1990) Teratogenicity of carbamazepine in rats. Teratology 41: 311-317
140. Pereira M. E., Rosat R., Huang C. H., Godoy M. G. and Izquierdo I. (1989) Inhibition by diazepam of the effect of additional training and of extinction on the retention of shuttle avoidance behavior in rats. Behav. Neurosci. 103: 202-205
141. Holley L. A., Turchi J., Apple C. and Sarter M. (1995) Dissociation between the attentional effects of infusions of a benzodiazepine receptor agonist and an inverse agonist into the basal forebrain. Psychopharmacology (Berl) 120: 99-108
142. Bittigau P., Sifringer M., Genz K., Reith E., Pospischil D., Govindarajalu S. et al. (2002) Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc. Natl. Acad. Sci. USA 99: 15089-15094
143. Jevtovic-Todorovic V., Hartman R. E., Izumi Y., Benshoff N. D., Dikranian K., Zorumski C. F. et al. (2003) Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J. Neurosci. 23: 876-882
144. Paulson R. B., Sucheston M. E., Hayes T. G. and Paulson G. W. (1985) Teratogenic effects of valproate in the CD-1 mouse fetus. Arch. Neurol. 42: 980-983
145. Faiella A., Wernig M., Consalez G. G., Hostick U., Hoffman C., Hustert E. et al. (2000) A mouse model for valproate teratogenicity: parental effects, homeotic transformation, and altered HOX expression. Hum. Mol. Genet. 9: 227-236
146. Finnell R. H., Gelineau-van Waes J., Eudy J. D. and Rosenquist T. H. (2002) Molecular basis of environmentally induced birth defects. Annu. Rev. Pharmacol. Toxicol. 42: 181-208
147. Phiel C. J., Zhang F., Huang E. Y., Guenther M. G., Lazar M. A. and Klein P. S. (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer and teratogen. J. Biol. Chem. 276: 26724-26731
148. Gottlicher M., Minucci S., Zhu P., Kramer O. H., Schimpf A., Giavara S. et al. (2001) Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 29: 6969-6978
149. Martin M. L. and Regan C. M. (1991) The anticonvulsant valproate teratogen restricts the glial cell cycle at a defined point in the mid G1 phase. Brain Res. 554: 223-228
150. Vorhees C. V. (1987) Behavioral teratogenicity of valproic acid: selective effects on behavior after prenatal exposure to rats. Psychopharmacology 92: 173-179
151. Ingram J. L., Peckham S. M., Tisdale B. and Rodier P. M. (2000) Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism. Neurotoxicol. Teratol. 22: 319-324
152. Bolanos A. R., Sarkisian M., Yang Y., Hori A., Helmers S. L., Mikati M. et al. (1998) Comparison of valproate and phenobarbital treatment after status epilepticus in rats. Neurology 51: 41-48
153. Cha B. H., Silveira D. C., Liu X., Hu Y. and Holmes G. L. (2002) Effect of topiramate following recurrent and prolonged seizures during early development. Epilepsy Res. 51: 217-232
154. Koh S and Jensen F. E. (2001) Topiramate blocks perinatal hypoxia-induced seizures in rat pups. Ann. Neurol. 50: 366-372
155. Buehler B. A., Rao V. and Finnell R. H. (1994) Biochemical and molecular teratology of fetal hydantoin syndrome. Neurol. Clin. 12: 741-748
156. Jensen F. E., Blume H., Alvarado S., Firkusny I. And Geary C. (1995) NBQX blocks acute and late epileptogenic effects of perinatal hypoxia. Epilepsia 36: 966-972
157. Cilio M. R., Bolanos A. R., Liu Z., Schmid R., Yang Y., Stafstrom C. E. et al. (2001) Anticonvulsant action and long-term effects of gabapentin in the immature brain. Neuropharmacology 40: 139-147
158. Schmitt U. and Hiemke C. (2002) Tiagabine, a gamma-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze. Behav. Brain Res. 133: 391-394
159. Bryant R. C., Petty F. and Byrne W. L. (1973) Effects of piracetam (SKF 38462) on acquisition, retention and activity in the goldfish. Psychopharmacologia 29: 121-130
160. Wolthuis O. L. (1981) Behavioural effects of etiracetam in rats. Pharmacol. Biochem. Behav. 15: 247-255
161. Verloes R., Scotto A. M., Gobert J. and Wülfert E. (1988) Effects of nootropic drugs in a scopolamine-induced amnesia model in mice. Psychopharmacology 95: 226-230
162. Lamberty Y., Margineanu D. G. and Klitgaard H. (2000) Absence of negative impact of levetiracetam on cognitive function and memory in normal and amygdala-kindled rats. Epilepsy Behav. 1: 333-342
163. Hori M., Ito T., Oka M., Noda Y., Matsuno Y., Furukawa K. et al. (1987) General pharmacology of the novel antiepileptic compound zonisamide. First communication: Effects on central nervous system. Arzneimittelforschung 37: 1124-1130
164. Dobbing J., Sands J. and Gratrix C. A. (1979) Cell size and cell number: a reconsideration of organ growth and catch-up potential. Proc. Nutr. Soc. 38: 99A
165. Ishimaru, M. J., Ikonomidou C. , Tenkova T. I., Der T. C., Dikranian K., Sesma M. A. et al. (1999) Distinguishing excitotoxic from apoptotic neurodegeneration in the developing rat brain. J. Comp. Neurol. 408: 461-476
166. Glier C., Dzietko M., Bittigau P., Jarosz B., Korobowicz E. and Ikonomidou C. (2004) Therapeutic doses of topiramate are not toxic to the developing brain. Exp. Neurol. 185: 403-409
167. Manthey D., Asimiadou S., Stefovska V., Kaindl A. M., Fassbender J., Ikonomidou C. et al. (2005) Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain. Exp. Neurol. 193: 497-503
168. Ohmori H., Yamashita K., Hatta T., Yamasaki S., Kawamura M., Hogashi Y. et al. (1997) Effects of low-dose phenytoin administered to newborn mice on developing cerebellum. Neurotoxicol. Teratol. 19: 205-211
169. Ohmori H., Ogura H., Yasuda M., Nakamura S., Hatta T., Kawano K. et al. (1999) Developmental neurotoxicity of phenytoin on granule cells and Purkinje cells in mouse cerebellum. J. Neurochem. 72: 1497-1506
170. Yan G. M., Irwin R. P., Liu S. Z., Weller M., Wood K. A. and Paul S. M. (1995) Diphenylhydanthoin induces apoptotic cell death of culture rat cerebellar granule neurons. J. Pharmacol. Exp. Ther. 274: 983-990
171. Blank N. K., Nishimura R. N. and Seil F. J. (1982) Phenytoin neurotoxicity in developing mouse cerebellum in tissue culture. J. Neurol. Sci. 55: 91-97
172. Neale E. A., Sher P. K., Granbard B. I., Habig M., Fitzgerald S. C. and Nelson P. G. (1985) Differential toxicity of chronic exposure to phenytoin, phenobarbital or carbamazepine in cerebral cortical cell cultures. Pediatr. Neurol. 1: 143-150
173. Hansen H. H., Briem T., Dzietko M., Sifringer M., Rzeski W., Zdzisinska B. et al. (2004) Mechanisms leading to disseminated apoptosis following NMDA receptor blockade in the developing rat brain. Neurobiol. Dis. 16: 440-453
174. Hardingham G. E. and Bading H. (2003) The Yin and Yang of NMDA receptor signalling. Trends Neurosci. 26: 81-89
175. Asimiadou S., Bittigau P., Felderhoff-Mueser U., Manthey D., Sifringer M., Pesditschek S. et al. (2005) Protection with estradiol in developmental models of apoptotic neurodegeneration. Ann. Neurol., in press
176. Pawlikowski M., Stepien H., Mroz-Wasilewska Z. and Pawlikowska A. (1987) Effects of diazepam on cell proliferation in cerebral cortex, anterior pituitary and thymus of developing rats. Life Sci. 40: 1131-1135
177. Laeng P., Pitts R. L., Lemire A. L., Drabik C. E., Weiner A., Tang H. et al. (2004) The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells. J. Neurochem. 91: 238-251
178. Ogura H., Yasuda M., Nakamura S., Yamashita H., Mikoshiba K. and Ohmori H. (2002) Neurotoxic damage of granule cells in the dentate gyrus and the cerebellum and cognitive deficit following neonatal administration of phenytoin in mice. J. Neuropathol. Exp. Neurol. 61: 956-967
179. Jackson G. D., Williams S. R., Weller R. O., van Bruggen N., Preece N. E., Williams S. C. et al. (1994) Vigabatrin-induced lesions in the rat brain
180. Wong W. T. and Wong R. O. (2001) Changing specificity of neurotransmitter regulation of rapid dendritic remodeling during synaptogenesis. Nat. Neurosci. 4: 351-352
181. Bashir Z. I., Bortolotto Z. A., Davies C. H., Berretta N., Irving A. J., Seal A. J. et al. (1993) Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature 363: 347-350
182. Luthi A., Schwyzer L., Mateos J. M., Gahwiler B. H. and McKinney R. A. (2001) NMDA receptor activation limits the number of synaptic connections during hippocampal development. Nat. Neurosci. 4: 1102-1107
183. Brooks W. J., Petit T. L. and LeBoutillier J. C. (1997) Effect of chronic administration of NMDA antagonists on synaptic development. Synapse 26: 104-113
184. Serrano E. E., Kunis D. M. and Ransom B. R. (1988) Effects of chronic phenobarbital exposure on cultured mouse spinal cord neurons. Ann. Neurol. 24: 429-438
185. Bergey G. K., Swaiman K. F., Schrier B. K., Fitzgerald S. and Nelson P. G. (1981) Adverse effects of phenobarbital on morphological and biochemical development of fetal mouse spinal cord neurons in culture. Ann. Neurol. 9: 584-589
186. Ogura H., Yasuda M., Nakamura S., Yamashita H., Mikoshiba K. and Ohmori H. (2002) Neurotoxic damage of granule cells in the dentate gyrus and the cerebellum and cognitive deficit following neonatal administration of phenytoin in mice. J. Neuropathol. Exp. Neurol. 61: 956-967
187. Kempermann G. and Volk B. (1995) Phenytoin inhibits expression of microtubule-associated protein 2 and influences cell-viability and neurite growth of cultured cerebellar granule cells. Brain Res. 687: 194-198
188. Caceres A., Mautino J. and Kosik K. S. (1992) Suppression of MAP2 in cultured cerebellar macroneurons inhibits minor neurite formation. Neuron 9: 607-618
189. McKinney R. A., Capogna M., Dürr R., Gahwiler B. H. and Thompson S. M. (1999) Miniature synaptic events maintain dendritic spines via AMPA receptor activation. Nat. Neurosci. 2: 44-49
190. Bear M. F., Kleinschmidt A., Gu Q. and Singer W. (1990) Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist. J Neurosci. 10: 909-925
191. Rocha M. and Sur M. (1995) Rapid acquisition of dendritic spines by visual thalamic neurons after blockade of N-methyl-D-aspartate receptors. Proc. Natl. Acad. Sci. USA 92: 8026-8030
192. Brewer G. J. and Cotman C. W. (1989) NMDA receptor regulation of neuronal morphology in cultured hippocampal neurons. Neurosci. Lett. 99: 268-273
193. Fox K., Schlaggar B. L., Glazewski S. and O'Leary D. D. (1996) Glutamate receptor blockade at cortical synapses disrupts development of thalamocortical and columnar organization in somatosensory cortex. Proc. Natl. Acad. Sci. USA 93: 5584-5589
194. Laeng P., Pitts R. L., Lemire A. L., Drabik C. E., Weiner A., Tang H. et al. (2004) The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells. J. Neurochem. 91: 238-251
195. Smith-Swintosky V. L., Zhao B., Shank R. P. and Plata-Salaman C. R. (2001) Topiramate promotes neurite outgrowth and recovery of function after nerve injury. Neuroreport 12: 1031-1034
196. Cohen J. A., Fisher R. S., Brigell M. G., Peyster R. G. and Sze G. (2000) The potential for vigabatrin-induced intramyelinic edema in humans. Epilepsia 41: 148-157
197. Sidhu R. S., Del Bigio M. R., Tuor U. I. and Seshia S. S. (1997) Low-dose vigabatrin (gamma-vinyl GABA)-induced damage in the immature rat brain. Exp. Neurol. 144: 400-405
198. Qiao M., Malisza K. L., Del Bigio M. R., Kozlowski P., Seshia S. S. and Tuor U. I. (2000). Effect of long-term vigabatrin administration on the immature rat brain. Epilepsia 41: 655-665
199. Fishman R. H., Ornoy A. and Yanai J. (1989) Correlated ultrastructural damage between cerebellum cells after early anticonvulsant treatment in mice. Int. J. Dev. Neurosci. 7: 15-26
200. Patsalos P. N. and Wiggins R. C. (1982) Brain maturation following administration of phenobarbital, phenytoin and sodium valproate to developing rats or to their dams: effects on synthesis of brain myelin and other subcellular membrane proteins. J. Neurochem. 39: 915-923
201. Trotter A. and Pohlandt. F. (2000) The replacement of oestradiol and progesterone in very premature infants. Ann. Med. 32: 608-614