Biomedical subjects

Eef L Theunissen

Publications and source records attributed to Eef L Theunissen.

6 recordsLinked to original sources

PubMed2006

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

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 ([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.

Adult↗

PubMed2006

High-potency marijuana impairs executive function and inhibitory motor control.

Human performance studies have usually relied on low-potency marijuana (4% THC) for determining THC-induced impairment. The present study was designed to assess the effects of high-potency marijuana (13% THC) on human performance. In all, 20 recreational users of marijuana participated in a double-blind, placebo controlled, three way cross-over study. The treatments consisted of single doses of 0, 250, and 500 microg/kg THC. Performance tests were conducted at regular intervals between 15 min and 6 h postsmoking and included measures of motor control (Critical tracking task), executive function (Tower of London) motor impulsivity (Stop signal task), and risk taking (Iowa gambling task). THC significantly impaired performance in the Critical tracking task and decreased the number of correct decisions in the Tower of London task. In addition, THC significantly increased stop reaction time and the proportions of commission and omission errors in the Stop signal task. THC-induced impairments lasted up to 6 h postsmoking as indicated by the absence of a THC x Time after smoking interaction. Effect sizes for performance impairments produced by THC 250 microg/kg were relatively low but generally increased by a factor of two in case of THC 500 microg/kg. These data suggest that high potency marijuana consistently impairs executive function and motor control. Use of higher doses of THC in controlled studies may offer a reliable indication of THC induced impairment as compared to lower doses of THC that have traditionally been used in performance studies.

Adult↗

PubMed2006

Repeated-dose effects of mequitazine, cetirizine and dexchlorpheniramine on driving and psychomotor performance.

AIMS: Previous studies have demonstrated that the antihistamines mequitazine, cetirizine and dexchlorpheniramine produce mild sedation after single doses. It is unknown, however, whether acute sedation persists after repeated dosing. Therefore, this study assessed the effects of repeated dosing of these antihistamines on driving and psychomotor performance. METHODS: Sixteen healthy volunteers were treated with mequitazine 10 mg q.a.m., cetirizine 10 mg q.a.m., dexchlorpheniramine Repetab 6 mg b.i.d. and placebo for four separate 8-day periods. Drug effects were assessed on days 1 and 8 using on-the-road driving tests (highway driving and car following), psychomotor tests (tracking and divided attention) and subjective questionnaires. RESULTS: Dexchlorpheniramine and mequitazine significantly impaired driving performance on the highway driving test on the first day; dexchlorpheniramine increased Standard Deviation of Lateral Position by 2 cm [95% confidence interval (CI) 0.5, 3.8] and mequitazine by 2.5 cm (CI 1.0, 4.3). These effects on driving performance disappeared after 8 days of treatment. No effect of treatment was found on car following, tracking and divided attention. Although subjective ratings confirmed that subjects knew their driving had been impaired in the mequitazine and dexchlorpheniramine condition after completion of the highway driving test on day 1, they did not expect their driving to be affected before the start of the test. Cetirizine did not impair performance on any of the tests. CONCLUSIONS: Single doses of mequitazine 10 mg and dexchlorpheniramine Repetab 6 mg cause mild driving impairment. However, when taken over several days, the impairing effect wears off, possibly as a result of tolerance.

Administration, Oral↗

PubMed2006

Stimulating effects of H1-antagonists.

Whereas antihistamines are generally known for their sedative side effects, this review shows that several studies also found mild stimulating effects on performance for the H1-antagonists terfenadine, ebastine, fexofenadine and desloratadine. These stimulating effects were mostly demonstrated in tasks involving high levels of attention, e.g. divided attention tasks, vigilance tasks and driving tasks. The stimulating effects of these antihistamines were often dependent of the given dose; however the relation was not always linear. The mechanism responsible for the stimulating effects of these four antihistamines is still unclear, though it is hypothesized that it involves other neurotransmitters like dopamine and GABA, or that it acts through the H3 histamine receptor. Further research is needed to clarify the ambiguous role of histamine in processes of arousal. In addition, it would be useful to determine whether terfenadine, ebastine, fexofenadine and desloratadine can return allergic patient's performance back to their preclinical level.

Animals↗

PubMed2005

A combined neurophysiological and behavioural study into the stimulating effects of fexofenadine on performance.

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.

Adult↗

PubMed2003

Developmental changes in distinguishing concurrent auditory objects.

Children have considerable difficulties in identifying speech in noise. In the present study, we examined age-related differences in central auditory functions that are crucial for parsing co-occurring auditory events using behavioral and event-related brain potential measures. Seventeen pre-adolescent children and 17 adults were presented with complex sounds containing multiple harmonics, one of which could be 'mistuned' so that it was no longer an integer multiple of the fundamental. Both children and adults were more likely to report hearing the mistuned harmonic as a separate sound with an increase in mistuning. However, children were less sensitive in detecting mistuning across all levels as revealed by lower d' scores than adults. The perception of two concurrent auditory events was accompanied by a negative wave that peaked at about 160 ms after sound onset. In both age groups, the negative wave, referred to as the 'object-related negativity' (ORN), increased in amplitude with mistuning. The ORN was larger in children than in adults despite a lower d' score. Together, the behavioral and electrophysiological results suggest that concurrent sound segregation is probably adult-like in pre-adolescent children, but that children are inefficient in processing the information following the detection of mistuning. These findings also suggest that processes involved in distinguishing concurrent auditory objects continue to mature during adolescence.

Acoustic Stimulation↗