Stimulating effects of the antihistamine fexofenadine: testing the dopamine transporter hypothesis |
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Authors: | Eef L. Theunissen Marinus J. P. G. van Kroonenburgh Jeroen A. van Deursen Ciska Blom-Coenjaerts Johannes G. Ramaekers |
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Affiliation: | (1) Experimental Psychopharmacology Unit, Faculty of Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;(2) Department of Nuclear Medicine, University Hospital Maastricht, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands;(3) Experimental Psychopharmacology Unit, Department of Neurocognition, Faculty of Psychology, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands |
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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-2β-carbomethoxy-3β-[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.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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Keywords: | Antihistamine Fexofenadine Dopamine transporter Cognitive performance SPECT |
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