title: Cardiovascular risk assessment of atypical antipsychotic drugs in a zebrafish model.
abstract: The zebrafish model has been developed and evaluated for its ability to predict the toxicity of chemicals. Zebrafish additionally serve as an excellent model for assessing drug-induced cardiotoxicity, although zebrafish and mammalian hearts differ in structure. Recently, regulatory authorities have expressed concerns about a possible relationship between antipsychotics and risk of QTc interval prolongation, serious arrhythmia and sudden cardiac death. In the current study, we performed a cardiovascular risk assessment of six atypical antipsychotic drugs in zebrafish, specifically, aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone. Visual endpoints, such as lethality, edema (the presence of heart and trunk edema), hemorrhage (clustering of a pool of blood in an area outside the normal circulation), abnormal body shape (including bent or misshapen caudal region of the larvae) and motility, were evaluated as general toxicity endpoints, and the heart beat rate calculated as the cardiovascular toxicity endpoint. The zebrafish model facilitates determination of the heart beat rate, and may thus be an attractive screening tool for cardiovascular risk assessment of atypical antipsychotic drugs to understand the variations in response to QT-prolonging drugs.
authors: Department of Animal Science and Biotechnology, Chungnam National University, Yuseong-gu, Gung-dong 220, Daejeon, 305-764, Korea.
authors: Sung Hak
authors: SH
authors: Lee
authors: Hong Rye
authors: HR
authors: Kim
authors: Rong Xun
authors: RX
authors: Han
authors: Reza K
authors: RK
authors: Oqani
authors: Dong Il
authors: DI
authors: Jin
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D023381:Endpoint Determination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007814:Larva; D007928:Lethal Dose 50; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018570:Risk Assessment; D015027:Zebrafish / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents