M. Yoshii et al., Cellular mechanism of action of cognitive enhancers: Effects of nefiracetam on neuronal Ca2+ channels, ALZ DIS A D, 14, 2000, pp. S95-S102
Cellular mechanisms underlying the cognition-enhancing actions of piracetam
-like nootropics were studied by recording Ca2+ channel currents from neuro
blastoma x glioma hybrid (NG108-15) cells and Xenopus oocytes expressing Ca
2+ channels. In NG108-15 cells, nefiracetam (1 mu M) produced a twofold inc
rease in L-type Ca2+ channel currents. A similar. but slightly less potent
effect was observed with aniracetam. whereas piracetam and oxiracetam exert
ed no such effects. Cyclic AMP analogs mimicked the nefiracetam action. N-t
ype Ca2+ channel currents inhibited by leucine (Leu)-enkephalin by means of
inhibitory G proteins (Go/Gi) were recovered promptly by nefiracetam, wher
eas those inhibited by prostaglandin E1 via stimulatory G proteins were not
affected by nefiracetam. Cells treated with pertussis toxin (500 ng/mL, >
20 hours) were insensitive to nefiracetam. In Xenopus oocytes functionally
expressing N-type (alpha(1B)) Ca2+ channels and delta-opioid receptors, nef
iracetam was also effective in facilitating the recovery from Leu-enkephali
n-induced inhibition. These results suggest that nefiracetam, and possibly
aniracetam, may activate N- and L-type Ca2+ channels in a differential way
depending on how they recover from Go/Gi-mediated inhibition.