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.
Yamada
K
K
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Nakayama
S
S
Shiotani
T
T
Hasegawa
T
T
Nabeshima
T
T
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009355:Neomycin / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002491:Central Nervous System Agents; D011760:Pyrrolidinones; C058876:nefiracetam; D012601:Scopolamine; D009355:Neomycin