title: Teratogenic potential of antiepileptic drugs in the zebrafish model.
abstract: The zebrafish model is an attractive candidate for screening of developmental toxicity during early drug development. Antiepileptic drugs (AEDs) arouse concern for the risk of teratogenicity, but the data are limited. In this study, we evaluated the teratogenic potential of seven AEDs (carbamazepine (CBZ), ethosuximide (ETX), valproic acid (VPN), lamotrigine (LMT), lacosamide (LCM), levetiracetam (LVT), and topiramate (TPM)) in the zebrafish model. Zebrafish embryos were exposed to AEDs from initiation of gastrula (5.25 hours post-fertilization (hpf)) to termination of hatching (72 hpf) which mimic the mammalian teratogenic experimental design. The lethality and teratogenic index (TI) of AEDs were determined and the TI values of each drug were compared with the US FDA human pregnancy categories. Zebrafish model was useful screening model for teratogenic potential of antiepilepsy drugs and was in concordance with in vivo mammalian data and human clinical data.
authors: Department of Animal Science & Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Sung Hak
authors: SH
authors: Lee
authors: Jung Won
authors: JW
authors: Kang
authors: Tao
authors: T
authors: Lin
authors: Jae Eun
authors: JE
authors: Lee
authors: Dong Il
authors: DI
authors: Jin
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D005013:Ethosuximide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000078334:Lacosamide; D000077213:Lamotrigine; D000077287:Levetiracetam; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011247:Pregnancy; D064793:Teratogenesis / Q000187:drug effects*; D000077236:Topiramate; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D014481:United States; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use; D015027:Zebrafish / Q000254:growth & development*
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D000077287:Levetiracetam; D000078334:Lacosamide; D005013:Ethosuximide; D014635:Valproic Acid; D000077213:Lamotrigine; D010889:Piracetam