It is known that sedation by H1 antihistaminic drugs can be reduced or avoided if slow release formulations are used for their administration, probably because of a slower increase of the
drug concentration in plasma and brain. The aim of this study was to compare two different formulations of
dimenhydrinate (CAS 523-87-5), a single fast release
tablet with three
chewing gums (divided dose principle), with regard to their efficacy in a
motion sickness model and their detrimental effect on vigilance and central nervous system (CNS) performance. Caloric stimulation of the eardrum (air at 44 degrees C) was used to induce the symptoms of
motion sickness in 24 symptomatic volunteers in a three-way cross-over design comparing three
chewing gums (
Superpep forte, chewed for 30 min each) containing 20 mg dimenthydrinate each with a 50 mg
dimenhydrinate tablet and placebo. During caloric stimulation the following parameters were measured in order to compare efficacy: Quantitative analysis of
sodium excretion by sweat (main target parameter), subjective well being (
vertigo) by visual analogue scales (VAS) and frequency of
binocular nystagmus by computer nystagmography. Unwanted effects on vigilance and CNS performance were measured by means of the N1-P2 peak to peak amplitudes of auditory evoked potentials (AEPs) as an objective, quantitative parameter of vigilance and the latency to correct responses and the number of correct responses (complex choice reaction task) in the oculodynamic test (ODT) as parameters of complex choice reaction ability. As a main efficacy result
sodium excretion by sweat was markedly reduced by the
chewing gums and by the
tablet. The differences to placebo were highly significant (
chewing gums vs. placebo p < 0.0001,
tablet vs. placebo p < 0.0001). There was no relevant and no significant difference between both medications (p = 0.308). The secondary efficacy parameters, frequency of
binocular nystagm and the VAS
vertigo were markedly reduced by both medications in comparison to placebo, i.e. both medications were markedly effective. In both cases, however, this result failed statistical significance. The unwanted depressing effects on vigilance and CNS performance of the
chewing gums were less pronounced than that of
tablets. The N1/P2 peak-to-peak amplitudes of the AEPs were significantly reduced by both the
chewing gums and the
tablets. The effect of the
tablets was, however, larger than that of the
chewing gums. This highly significant (
tablet vs.
chewing gums, p = 0.0003) difference shows that the
tablet had a larger depressing effect on vigilance (greater sedation). In line with this result, the number of correct responses in the ODT was markedly and significantly reduced by the
tablet (p = 0.0027) but not significantly by the
chewing gums (p = 0.8140). The difference between the
tablet and the
chewing gums was highly significant (p = 0.0052). The complex choice reaction time was markedly and nearly significantly (p = 0.0558) prolonged by the
tablet whereas the
chewing gums produced only a very small and insignificant prolongation. That the objective measurements of vigilance and CNS performance showed significantly larger detrimental effects of the
tablet than of the
chewing gums is probably a consequence of a faster increase of the
dimenhydrinate concentration in the CNS after administration of the
tablet in comparison to the divided dose principle of the
chewing gums.