Stimulating effects of the antihistamine fexofenadine: testing the dopamine transporter hypothesis.
BACKGROUND
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 ([123I]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.
Theunissen
Eef L
EL
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
van Kroonenburgh
Marinus J P G
MJ
van Deursen
Jeroen A
JA
Blom-Coenjaerts
Ciska
C
Ramaekers
Johannes G
JG
D000328:Adult; D003071:Cognition / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D006634:Histamine H1 Antagonists; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D016593:Terfenadine; C093230:fexofenadine