Possible involvement of the activation of voltage-sensitive calcium channels in the ameliorating effects of nefiracetam on scopolamine-induced impairment of performance in a passive avoidance task

We investigated the effects of various types of calcium channel antagonists on the amelioration by nefiracetam [N-(2,6-dimethylphenyl)-2-(2- oxo-1-pyrrolidinyl) acetamide, DM-9384] of scopolamine-induced impairment of performance in a passive avoidance task in mice. The reversal of the scopolamine-induced impairment of performance by nefiracetam showed a bell- shaped plot. Both i.p. and i.c.v. injection of L-type calcium channel antagonists such as nifedipine and flunarizine attenuated the ameliorating effects of nefiracetam, although diltiazem had no effect. Neomycin, an N- type calcium channel antagonist, also attenuated these effects of nefiracetam in a dose-dependent manner. Further, LaCl₃ but not NiCl₂ showed inhibitory effects on the amelioration by nefiracetam. These results suggest that the activation of high-voltage-activated, but not low-voltage-activated, calcium channels is involved in the ameliorating effects of nefiracetam on scopolamine-induced impairment of performance in a passive avoidance task.