A combined neurophysiological and behavioural study into the stimulating effects of fexofenadine on performance.
ABSTRACT Antihistamines are known for their sedative effects. However, some studies suggested mild stimulant effects in the case of fexofenadine. The goals of this study are to examine whether fexofenadine possesses stimulating properties and to determine whether such stimulating effects are related to workload. Sixteen healthy volunteers received a single dose of 180 and 360 mg fexofenadine and placebo on separate test days. Drug effects were assessed using a divided attention task (DAT), continuous performance task (CPT) and motor choice reaction time test (MCRT). Sensitivity of the tasks was increased by manipulating the workload during task performance. Event Related brain Potentials (ERPs) were measured in the DAT and CPT to study the underlying neurophysiological processes. An interaction effect of Treatment and Workload was found on tracking performance in the DAT and on movement time in the MCRT. Performance on the DAT was less affected by increments in workload after fexofenadine as compared to placebo. P1 and P3 latency were affected by Treatment x Workload and Treatment respectively and indicated faster attentional and information processing latencies following fexofenadine treatment. Treatment did not influence performance in the CPT task or in the ERPs measured during this task. The MCRT demonstrated faster movement times following fexofenadine treatment. These results suggest that although the neurophysiological data indicate central nervous system (CNS) activation after fexofenadine treatment, the magnitude of the centrally activating effects is too small to produce relevant performance improvement at the behavioural level.
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ABSTRACT: Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two participants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.Journal of Psychopharmacology 11/2011; 25(11):1517-23. · 3.37 Impact Factor
- Journal of clinical psychopharmacology 04/2013; 33(2):276-9. · 5.09 Impact Factor
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ABSTRACT: RATIONALE: P-glycoprotein (P-gp) is a drug efflux pump expressed, amongst others, on the luminal surface of the cerebral endothelial cells forming the blood-brain barrier. Studies in rodents have demonstrated that antihistamines that are substrates of the P-gp transporter display no or minor central nervous system (CNS) effects as compared to antihistamines that are not P-gp transporter substrates. OBJECTIVES: The present study explored whether P-gp contributes in similar ways to the occurrence of sedative effects of antihistamines in humans. METHODS: An fMRI study was conducted according to a double-blind, randomized, placebo-controlled, cross-over design in 13 healthy volunteers. Participants received cetirizine 15 mg (an antihistamine), verapamil 120 mg (a P-gp blocker), a combination of cetirizine + verapamil, and a placebo. Brain activity was assessed while conducting the attention network test (ANT) in a 3T magnetic resonance scanner. The ANT measures three independent attention domains: i.e., alerting, orienting, and executive attention. It was expected that the combined treatment of cetirizine with verapamil would prevent efflux of cetirizine from the CNS, thus increasing attentional impairment, as compared to cetirizine administered alone. RESULTS: The present study provides evidence that the P-gp transporter is involved in central antihistamine effects in humans. Participants were less alert during the combined treatment of cetirizine and verapamil as indicated by longer reaction times and decreased blood oxygen level-dependent response in the right superior temporal gyrus. CONCLUSION: It is concluded that the affinity for the P-gp transporter may contribute to the lower incidence of CNS side effects of certain antihistamines.Psychopharmacology 04/2013; · 4.06 Impact Factor