Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment

Margot A. Cousin, Jon Owen Ebbert, Amanda R. Wiinamaki, Mark D. Urban, David P. Argue, Stephen C Ekker, Eric W Klee

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 physicianvetted 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.

Original languageEnglish (US)
Article numbere90467
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 21 2014

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Drug Repositioning
Tobacco Use Disorder
Tobacco
nicotine
Zebrafish
United States Food and Drug Administration
Nicotine
Danio rerio
drug therapy
tobacco
drugs
Smoking Cessation
Pharmaceutical Preparations
Cause of Death
Ethanol
apomorphine
ethanol
death
health care costs
Phase II Clinical Trials

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment. / Cousin, Margot A.; Ebbert, Jon Owen; Wiinamaki, Amanda R.; Urban, Mark D.; Argue, David P.; Ekker, Stephen C; Klee, Eric W.

In: PLoS One, Vol. 9, No. 3, e90467, 21.03.2014.

Research output: Contribution to journalArticle

Cousin, Margot A. ; Ebbert, Jon Owen ; Wiinamaki, Amanda R. ; Urban, Mark D. ; Argue, David P. ; Ekker, Stephen C ; Klee, Eric W. / Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment. In: PLoS One. 2014 ; Vol. 9, No. 3.
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