Vincamine and vincanol are potent blockers of voltage-gated Na+ channels

The effects of three vinca derivatives on [H-3]batrachotoxin binding in rat cortical synaptosomes, on the inhibition of whole-cell Na+ currents evoked in voltage-clamped cortical neurones of the rat, on the protection against veratridine-induced cell death in cortical cultures and on the maximal electroshock-induced seizures in mice were compared. Vinpocetine, vincamine and vincanol reduced [H-3]batrachotoxin binding with IC50 values of 0.34, 1.9 and 10.7 mu M, blocked Na+ currents with IC50 values of 44, 72 and 30 mu M, and protected cortical cultures against veratridine-induced cell death with IC50 values of 0.49, 26 and 33 mu M, respectively. Upon i.p. administration, vinpocetine, vincamine and vincanol attenuated maximal electric shock-induced convulsions in a dose-dependent manner with ED(50) values of 27, 15.4 and 14.6 mg/kg, respectively. The present findings indicate that the three vinca derivatives are potent blockers of voltage-gated Na+ channels, a mechanism that may contribute at least in part to the pharmacological/therapeutic benefit of these drugs.