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.
Author(s): Philipova D, Tzenova B, Iwanowitsch A, Bognar-Steinberg I.
Affiliation(s): Institute of Physiology, Laboratory of Motor Control, Bulgarian Academy of
Sciences, Sofia, Bulgaria.
Publication date & source: 2004, Int J Clin Pharmacol Ther. , 42(4):218-31
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.
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