The DOI matches its Crossref record; 179 of the 179 references it cites were found in a registry or an index.
Antiepileptic drugs and the developing brain
Open accessAbstract
Epilepsy is the most common neurological disorder in young humans. Antiepileptic drugs (AEDs) which are used to treat seizures in infants, children and pregnant women can cause cognitive impairment, microcephaly and birth defects. Ion channels, neurotransmitters and second messenger systems constitute molecular targets of AEDs. The same targets regulate brain processes essential both for propagation of seizures and for learning, memory and emotional behavior. Thus, AEDs can influence brain function and brain development in undesired ways. Here we review mechanisms of action of AEDs, examine clinical evidence for their adverse effects in the developing human brain, and present studies on cognitive and behavioral effects in animal models. Furthermore, we discuss mechanisms responsible for adverse effects of AEDs in the developing mammalian brain, including interference with cell proliferation and migration, axonal arborization, synaptogenesis, synaptic plasticity and physiological apoptotic cell death.
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“Important is also that the anti-epileptic drugs, given at young age or during pregnancy, can have major neurodevelopmental implications as well.”
From Development of prefrontal cortex (2022) · cites this paper as [391]
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Cites
Glutamate receptor ion channels
Mayer, M. L. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.004 · Cited by 3,655
Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain
Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vöckler, J., Dikranian, K., Tenkova, T. I., Stefovska, V., Turski, L., & Olney, J. W. (1999) · Science · doi:10.1126/science.283.5398.70 · Cited by 2,055
Self-citationJevtovic-Todorovic, V., Hartman, R. E., Izumi, Y., Benshoff, N. D., Dikranian, K., Zorumski, C. F., Olney, J. W., & Wozniak, D. F. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00876.2003 · Cited by 1,983
Macdonald, R. L., & Olsen, R. W. (1994) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.17.030194.003033 · Cited by 1,975
Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
Göttlicher, M., Minucci, S., Zhu, P., Krämer, O. H., Schimpf, A., Giavara, S., Sleeman, J. P., Coco, F. L., Nervi, C., Pelicci, P. G., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.6969 · Cited by 1,930
Phiel, C. J., Zhang, F., Huang, E. Y., Guenther, M. G., Lazar, M. A., & Klein, P. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101287200 · Cited by 1,758
Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels
Perez‐Reyes, E. (2003) · Physiological Reviews · doi:10.1152/physrev.00018.2002 · Cited by 1,655
Ethanol-Induced Apoptotic Neurodegeneration and Fetal Alcohol Syndrome
Ikonomidou, C., Bittigau, P., Ishimaru, M. J., Wozniak, D. F., Koch, C. A., Genz, K., Price, M. T., Stefovska, V. G., Hörster, F., Tenkova, T., et al. (2000) · Science · doi:10.1126/science.287.5455.1056 · Cited by 1,382
Self-citationThe neurobiology of antiepileptic drugs
Rogawski, M. A., & Löscher, W. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1430 · Cited by 1,243
Benzodiazepine actions mediated by specific γ-aminobutyric acidA receptor subtypes
Rudolph, U., Crestani, F., Benke, D., Brünig, I., Benson, J. A., Fritschy, J.-M., Martin, J. R., Bluethmann, H., & Möhler, H. (1999) · Nature · doi:10.1038/44579 · Cited by 1,172
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Ichitani, M., Kitoh, S., Tanaka, K., Fujinami, S., Suda, M., Honda, M., & Kunimoto, K. (2014) · European Journal of Chemistry · doi:10.5155/eurjchem.5.1.6-10.933 · Cited by 1
Thio, L. L., & Dodson, W. E. (2010) · Neurology · doi:10.1212/wnl.0b013e3181d1cd65 · Cited by 1
Liang, L., Yu, F., Hongbin, Sun, ̆, Y., Yan, Xie, Baoming, He, & Xu (2010) · 中国神经再生研究：英文版
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Hamed, S. A. (2012) · Journal of Pediatric Epilepsy · doi:10.3233/pep-2012-004
“diazepam, PB, VPA CBZ, PHT, LTG, VGB, TPM and LEV) have been shown to induce widespread neuronal apoptosis in immature animal brains at plasma concentrations relevant for seizure control in humans [157,158].”
BackgroundProteome changes associated with developmental defects following perinatally acquired brain damage
Kaindl, A. M. (2009) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-16753
Self-citationPassemard, S., Kaindl, A. M., Verche, V. L., Dournaud, P., & Gressèns, P. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511711848.006
Self-citationANTI-EPILEPTIC DRUGS AND BRAIN AND BEHAVIOURAL DEVELOPMENT IN ANIMAL MODELS AND HUMANS
Adab, N., & O’Donoghue, M. (2010) · Fetal and Maternal Medicine Review · doi:10.1017/s0965539510000100
PEDIATRIC EPILEPSY | Age-Specific Responses to Antiepileptic Drugs
Galanopoulou, A. S., & Moshé, S. L. (2009) · Elsevier eBooks · doi:10.1016/b978-012373961-2.00261-7
Antiepileptic Drugs, Cognition and Neurodevelopment
Eadie, M. J., & Vajda, F. J. E. (2015) · Springer eBooks · doi:10.1007/978-3-319-21434-4_10
Lamberink, H. J. (2021) · Utrecht University Repository (Utrecht University) · doi:10.33540/431
Silva, W. H., & Vaucheret, E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819641-0.00129-8
Yu, S., Sousa, N., & Almeida, O. F. X. (2015) · Springer eBooks · doi:10.1007/978-3-642-36172-2_385
Yu, S., Sousa, N., & Almeida, O. F. X. (2010) · Springer eBooks · doi:10.1007/978-3-540-68706-1_385
Yu, S., Sousa, N., & Almeida, O. F. X. (2014) · Springer eBooks · doi:10.1007/978-3-642-27772-6_385-2
El‐Gamal, K. M., El-Morsy, A., Sherbiny, F. F., Elraheim, A. S., Ayaad, R., Saad, A., Al-Omary, F. A. M., & Mansour, B. (2022) · Delta University Scientific Journal · doi:10.21608/dusj.2022.275430
Early neurodevelopmental follow‐up results from the NEOLEV2 cohort
Sharpe, C. M., Reiner, G., Reed, P., Joe, P., Wilson, F., Davis, S. L., Lee, L., Wang, S. G., Gold, J. J., & Haas, R. (2025) · Annals of the Child Neurology Society · doi:10.1002/cns3.20096
Traumatic Brain Injury in Children
Viamonte, M., Giza, C. C., & Ferrazzano, P. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-10944-7.00122-0
Jalilzadeh, H., Feyzi-barnaji, B., Mohammadi, A., Amanlou, M., & Mohebbi, N. (2026) · Journal of Analytical Chemistry · doi:10.1134/s1061934825600982
Ogura, T., & Shiraishi, C. (2026) · Cureus · doi:10.7759/cureus.105027
“CNS disorders emerged as the most frequently reported category across all agents, consistent with their known pharmacologic effects on the developing brain [14] and the nature of epilepsy itself [15].”
Medication-Induced Neurotoxicity in Critically Ill Cancer Patients
Hsi, A. H., & Loghin, M. E. (2026) · Springer eBooks · doi:10.1007/978-3-319-74698-2_32-2
Metadata
- Authors
- Kaindl, A. M., Asimiadou, S., Manthey, D., Hagen, M. V. D., Turski, L., & Ikonomidou, C.
- Affiliations
- Stiftung Charité (DE)
- Technische Universität Dresden (DE)
- Solvay (Netherlands) (NL)
- Corresponding author
- Ikonomidou, C.
- Venue
- Cellular and Molecular Life Sciences CMLS
- Published
- 2006-01-02
- Volume
- 63
- Issue
- 4
- Pages
- 399-413
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11136147
- OpenAlex
- W1963567657
- Cited by
- 121
- References
- 179
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2022: 5 · 2021: 7 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 2 · 2015: 12 · 2014: 5 · 2013: 6 · 2012: 7
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- antiepileptic drugs, adverse drug reactions, developing brain, epilepsy, cognitive impairment, microcephaly, congenital malformations, ion channels, neurotransmitters, second messenger signaling, seizure propagation, learning and memory, behavioral effects, cell proliferation, neuronal migration, axonal arborization, synaptogenesis, synaptic plasticity, apoptosis, prenatal drug exposure
- MeSH terms
- Animals, Anticonvulsants, Brain, Epilepsy, Humans, Neurons, Apoptosis
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