Influence of an antivertiginous combination preparation of cinnarizine and dimenhydrinate on event-related potentials, reaction time and psychomotor performance--a randomized, double-blind, 3-way crossover study in healthy volunteers.

In the present comparative, double-blind, 3-way crossover study, possible effects of an antivertiginous combination preparation on event-related potentials (ERPs) and performance were investigated. Twenty-one healthy volunteers received 4 doses (within 24 h) of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevert, ARL), dimenhydrinate 50 mg, or a placebo, in randomized order at 1-week intervals. Auditory event-related potentials (ERPs), reaction time (RT) and psychometric tests were assessed before as well as 60 and 150 minutes after the intake of the 1st (Day 1) and the 4th (Day 2) dose of study medication. The evaluation was primarily based on the difference in the outcomes measured 150 min after the 4th dose (t5) and those before the start of medication intake (t0). None of the medications affected the latency and amplitude of the sensory ERP component N100, neither under passive listening nor under discrimination task conditions. The latency of P300 in response to the rare target tones (oddball paradigm and binary series), showed significant (p < 0.05) delays after 4 doses of dimenhydrinate (18-24 ms), and no significant differences between ARL (3-17 ms) and either dimenhydrinate or placebo (4-13 ms). Responses to nontarget tones remained almost unaffected after medication intake. The secondary analysis of the P300 amplitude showed the greatest decreases under DH in both active series, with no significant differences between ARL and either DH or placebo. The 3 medications did not significantly prolong RT nor did they impair the performance of psychometric tests, or cause significant shifts of current mood. The combination preparation ARL showed the lowest rate of adverse events (n = 1), followed by dimenhydrinate (n = 3) and placebo (n = 6). Two subjects withdrew because of adverse events, both after the intake of placebo. In conclusion, the results gave no evidence for an impairment of central information processing and psychomotor performance after multiple dosing with the fixed combination ARL in healthy volunteers, which might, when present, represent an adverse reaction limiting its use in antivertiginous therapy. No significant differences were found between ARL and placebo.

Influence of 3 antivertiginous medications on the vigilance of healthy volunteers.

In the present randomized, comparative, double-blind, 3-way crossover study, possible effects of 3 antivertiginous medications on vigilance were investigated. 30 healthy volunteers received single doses of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevert, ARL), dimenhydrinate 50 mg, or betahistine dimesylate 12 mg, in randomized order at 1-week intervals. Spontaneous brain electrical activity (EEG), acoustic late evoked potentials (ALEP) with P300, and reaction time were measured before and 90 (t90) and 180 minutes (t180) after drug intake. All 3 medications led to a delay of P300 (primary criterion) and a decrease of its amplitude. The maximum delay at t180 was found for dimenhydrinate (16.42 ms) and the lowest for betahistine (6.33 ms). Differences ARL vs dimenhydrinate and ARL vs betahistine were not statistically significant (p > 0.05). Spectral analysis of spontaneous EEG showed slight and similar decreases in the power in the a-band under dimenhydrinate and ARL (p = 0.07 and p = 0.03 with respect to baseline, respectively), but basically no change under betahistine. There was no effect on reaction time by either medication. None of the subjects reported drowsiness or any other adverse event. The findings confirm the reported suitability of P300 latency for measurement of drug effects on brain activity, but provide no indication of concomitant impairment of performance capacity by the tested drugs. Global assessment of the results suggests that the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg exerts only a minor effect on vigilance, not significantly different from betahistine, which is commonly regarded as a non-sedating antivertiginous drug