The effect of idebenone, an agent improving cerebral metabolism, on catecholamine secretion was examined using primary cultures of bovine adrenal chromaffin cells. Catecholamine secretion evoked by acetylcholine was markedly inhibited by idebenone, and this effect was concentration-dependent. In contrast, other cerebral metabolism-improving agents, such as hopantenate and propentofylline, failed to cause any significant effect on the secretion in the same concentration range. Furthermore, idebenone inhibited the secretion evoked by high K+, veratridine, and Ba2+, but failed to inhibit the secretion evoked by the Ca(2+)-ionophore A23187. Idebenone also inhibited the radioactive Ca2+ uptake stimulated by acetylcholine or high K+ under the conditions in which its inhibitory action on the secretion was observed. Nifedipine, a typical voltage-dependent Ca2+ channel blocker, inhibited the secretion evoked by high K+, and this inhibitory action on the secretion was markedly reduced by the presence of idebenone. The present results suggest that idebenone may inhibit the influx of extracellular Ca2+ into the cells presumably through its blocking action on the voltage-dependent Ca2+ channels, resulting in the inhibition of catecholamine secretion in the adrenal chromaffin cell.