Lack of effect of 5HT3 antagonist in mediating subjective and behavioral responses to cotinine

Dorothy K Hatsukami, Joni Jensen, Lisa H. Brauer, Marc Mooney, Susan Schulte, Mehmet Sofuoglu, Paul R. Pentel

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Previous studies have shown that cotinine, a metabolite of nicotine, may antagonize some of the therapeutic effects of nicotine. The mechanisms underlying cotinine's effects are unclear, but cotinine has been observed to increase serotonin levels in the brain. Thus, it is possible that blocking serotonin effects may antagonize the actions of cotinine, thereby reducing its impact on responses to nicotine. This study determined whether granisetron, a 5HT3 receptor antagonist, would enhance the efficacy of the nicotine patch. Subjects were randomly assigned to one of the three granisetron conditions (N=43 for 2 mg/day; N=43 for 1 mg/day; N=42 for 0 mg/day) and asked to take the assigned medication daily during 15 days of tobacco abstinence. Because we were interested in interactions between cotinine and serotonin, all groups were also treated with a 21-mg nicotine patch. Assessments of withdrawal symptoms were made for 1 week during baseline smoking and several times during the experimental period. There was a near but nonsignificant difference among groups on a measure of tobacco withdrawal and no significant differences on global measures of drug effects or physiological measures. The data do not strongly support the hypothesis that 5HT3 agonism is the mechanism by which cotinine offsets the effects of nicotine.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalPharmacology Biochemistry and Behavior
Issue number1
StatePublished - Apr 2003


  • 5HT antagonists
  • Cotinine
  • Nicotine patch
  • Nicotine withdrawal

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