Stimulating effects of the antihistamine fexofenadine: testing the dopamine transporter hypothesis

E.L. Theunissen*, M.J.P.H. van Kroonenburgh, J.A. van Deursen, C. Blom-Coenjaerts, J.G. Ramaekers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Rationale: First- and second-generation antihistamines are known to produce different degrees of sedation. However, a few studies have shown that the H1-antagonist fexofenadine produces mild stimulating effects. One hypothesis suggests that this is due to fexofenadine producing an increase in dopamine levels by blocking the dopamine transporter. Objective: In this study, it was investigated whether a high dose of fexofenadine blocks the dopamine transporter in the striatum. In addition, the effect of fexofenadine on cognitive performance and motor impulsivity was investigated. Methods: Sixteen healthy subjects were given either placebo or fexofenadine 360 mg. The binding potential of N-w-fluoropropyl-2 beta-carbomethoxy-3 beta-[4-iodophenyl] nortropane ([I-123]FP-CIT) was measured using single-photon emission computed tomography (SPECT). Cognitive performance was measured in 40 subjects (20 placebo, 20 fexofenadine) using a digit symbol substitution test (DSST) and a stop signal task. In addition, subjective and physiological effects of fexofenadine were observed. Results: The SPECT data demonstrated that there was no difference in the binding potential of FP-CIT at the dopamine transporter in the striatum between the placebo- and fexofenadine-treated subjects. The behavioral results showed that fexofenadine improved performance on the DSST at T (max) of the drug. Fexofenadine did not affect motor impulsivity, subjective experience, or physiological measures. Conclusions: No evidence was provided to support the hypothesis that fexofenadine stimulates performance by blocking the dopamine transporter. The behavioral data suggest that a high dose of fexofenadine can stimulate performance in cognitive tasks.
Original languageEnglish
Pages (from-to)95-102
Issue number1
Publication statusPublished - 1 Jan 2006

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