The mechanisms of action of calcium antagonists in the prophylactic treatment of migraine remain unclear. The most likely proposed mechanism seems to be via influence on the central nervous system, but the central effects of calcium entry blockers are insufficiently characterized. The aim of the present study was to investigate the central mechanisms behind the efficacy of cyclandelate in a double-blind placebo-controlled parallel-designed study using the contingent negative variation (CNV), an event-related slow potential for measuring cortical excitability and investigating preparation processes. The CNV recordings were performed in 25 females suffering from migraine without aura before treatment (baseline), after single dose administration of cyclandelate or placebo and after 8 weeks' treatment with cyclandelate (cyclandelate group, no.=15) or placebo (placebo group, no.=10). Cyclandelate reduced significantly the days with migraine and duration of migraine compared to placebo. In the cyclandelate group a significant reduction of all CNV components was observed and the changes in amplitudes compared to baseline were more pronounced after treatment. Placebo reduced the late CNV component only after single dose administration. There were no changes in the early and total CNV. Cyclandelate did not normalize the habituation of the slow negative potential. The results are discussed in terms of the influence of cyclandelate on cortical excitability and of the prevention of cortical spreading depression via antagonistic effect on calcium channels.