The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Drugs That Induce Repolarization Abnormalities Cause Bradycardia in Zebrafish
Open accessAbstract
Background— Drug-induced QT prolongation and torsades de pointes remain significant and often unpredictable clinical problems. Current in vitro preclinical assays are limited by biological simplicity, and in vivo models suffer from expense and low throughput. Methods and Results— During a screen for the effects of 100 small molecules on the heart rate of the zebrafish, Danio rerio , we found that drugs that cause QT prolongation in humans consistently caused bradycardia and AV block in the zebrafish. Of 23 such drugs tested, 18 were positive in this initial screen. Poor absorption explained 4 of 5 false-negative results, as demonstrated by microinjection. Overall, 22 of 23 compounds that cause repolarization abnormalities were positive in this assay. Antisense “knockdown” of the zebrafish KCNH2 ortholog yielded bradycardia in a dose dependent manner confirming the effects of reduction of repolarizing potassium current in this model. Classical drug-drug interactions between erythromycin and cisapride, as well as cimetidine and terfenadine, were also reproduced. Conclusion— This simple high-throughput assay is a promising addition to the repertoire of preclinical tests for drug-induced repolarization abnormalities. The genetic tractability of the zebrafish will allow the exploration of heritable modifiers of such drug effects.
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Cites
Effective targeted gene ‘knockdown’ in zebrafish
Nasevicius, A., & Ekker, S. C. (2000) · Nature Genetics · doi:10.1038/79951 · Cited by 2,483
Molecular and Cellular Mechanisms of Cardiac Arrhythmias
Keating, M. T., & Sanguinetti, M. C. (2001) · Cell · doi:10.1016/s0092-8674(01)00243-4 · Cited by 1,001
Allelic Variants in Long-QT Disease Genes in Patients With Drug-Associated Torsades de Pointes
Yang, P., Kanki, H., Drolet, B., Yang, T., Wei, J., Viswanathan, P. C., Hohnloser, S. H., Shimizu, W., Schwartz, P. J., Stanton, M., et al. (2002) · Circulation · doi:10.1161/01.cir.0000014448.19052.4c · Cited by 554
Variant of SCN5A Sodium Channel Implicated in Risk of Cardiac Arrhythmia
Splawski, I., Timothy, K. W., Tateyama, M., Clancy, C. E., Malhotra, A., Beggs, A. H., Cappuccio, F. P., Sagnella, G. A., Kass, R. S., & Keating, M. T. (2002) · Science · doi:10.1126/science.1073569 · Cited by 523
A common polymorphism associated with antibiotic-induced cardiac arrhythmia
Sesti, F., Abbott, G. W., Wei, J., Murray, K. T., Saksena, S., Schwartz, P. J., Priori, S. G., Roden, D. M., George, A. L., & Goldstein, S. A. N. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.180223197 · Cited by 479
Electrical heterogeneity within the ventricular wall
Antzelevitch, C., & Fish, J. (2001) · Basic Research in Cardiology · doi:10.1007/s003950170002 · Cited by 334
The genetic basis of variability in drug responses
Roden, D. M., & George Jr, A. L. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd705 · Cited by 292
Antzelevitch, C., Sun, Z.-Q., Zhang, Z.-Q., & Yan, G.-X. (1996) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(96)00377-4 · Cited by 278
Defective “pacemaker” current ( I h ) in a zebrafish mutant with a slow heart rate
Baker, K., Warren, K. S., Yellen, G., & Fishman, M. C. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4554 · Cited by 215
Sex, hormones, and repolarization
Pham, T. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00429-1 · Cited by 203
Cited by
Zebrafish as a Model Vertebrate for Investigating Chemical Toxicity
Hill, A. J., Teraoka, H., Heideman, W., & Peterson, R. E. (2005) · Toxicological Sciences · doi:10.1093/toxsci/kfi110 · Cited by 1,374
Self-citationZebrafish as tools for drug discovery
MacRae, C. A., & Peterson, R. T. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4627 · Cited by 1,204
Self-citationIncardona, J. P., Collier, T. K., & Scholz, N. L. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2003.11.026 · Cited by 833
Strähle, U., Scholz, S., Geisler, R., Greiner, P., Hollert, H., Rastegar, S., Schumacher, A., Selderslaghs, I., Weiss, C., Witters, H., et al. (2012) · Reproductive Toxicology · doi:10.1016/j.reprotox.2011.06.121 · Cited by 673
Genesis and Regulation of the Heart Automaticity
Mangoni, M. E., & Nargeot, J. (2008) · Physiological Reviews · doi:10.1152/physrev.00018.2007 · Cited by 600
Metadata
- Authors
- Milan, D. J., Peterson, T. A., Ruskin, J. N., Peterson, R. T., & MacRae, C. A.
- Venue
- Circulation
- Published
- 2003-03-18
- Volume
- 107
- Issue
- 10
- Pages
- 1355-1358
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2058207889
- Cited by
- 440
- References
- 19
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Milan, D. J., Peterson, T. A., Ruskin, J. N., Peterson, R. T., & MacRae, C. A. (2003). Drugs That Induce Repolarization Abnormalities Cause Bradycardia in Zebrafish. Circulation. https://doi.org/10.1161/01.cir.0000061912.88753.87
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