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

by
Theunissen EL, van Kroonenburgh MJ,
van Deursen JA, Blom-Coenjaerts C, Ramaekers JG.
Experimental Psychopharmacology Unit,
Department of Neurocognition,
Faculty of Psychology,
University of Maastricht,
P.O. Box 616, 6200 MD, Maastricht,
The Netherlands,
e.theunissen@psychology.unimaas.nl.
Psychopharmacology (Berl). 2006 May 23;


ABSTRACT

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-2beta-carbomethoxy-3beta-[4-iodophenyl] nortropane ([(123)I]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. CONCLUSION: 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.

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