PUBLICATION
Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment
- Authors
- Cousin, M.A., Ebbert, J.O., Wiinamaki, A.R., Urban, M.D., Argue, D.P., Ekker, S.C., Klee, E.W.
- ID
- ZDB-PUB-140513-295
- Date
- 2014
- Source
- PLoS One 9: e90467 (Journal)
- Registered Authors
- Cousin, Margot, Ekker, Stephen C., Klee, Eric W., Urban, Mark
- Keywords
- none
- MeSH Terms
-
- Animals
- Benzazepines/chemistry
- Drug Repositioning*
- Models, Animal*
- Nicotine/pharmacology
- Quinoxalines/chemistry
- Tobacco Use Disorder*
- United States
- United States Food and Drug Administration
- Varenicline
- Zebrafish*
- PubMed
- 24658307 Full text @ PLoS One
Citation
Cousin, M.A., Ebbert, J.O., Wiinamaki, A.R., Urban, M.D., Argue, D.P., Ekker, S.C., Klee, E.W. (2014) Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment. PLoS One. 9:e90467.
Abstract
Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping