Vincamine and vincanol are potent blockers of voltage-gated Na+ channels.
The effects of three vinca derivatives on [3H]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 [3H]batrachotoxin binding with IC50 values of 0.34, 1.9 and 10.7 microM, blocked Na+ currents with IC50 values of 44.72 and 40 microM, and protected cortical against veratridine-induced cell death with IC50 values of 0.49, 26 and 33 microM, respectively. Upon i.p. administration, vinpocetine, vincamine and vincanol attenuated maximal electric shock-induced convulsions in a dose-dependent manner with ED50 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.
Erdo
S A
SA
Laboratory of CNS Pharmacology, Chinoin Co., Budapest, Hungary.
Molnár
P
P
Lakics
V
V
Bence
J Z
JZ
Tömösközi
Z
Z
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects*; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000633:toxicity; D014748:Vinca Alkaloids / Q000494:pharmacology*; D014749:Vincamine / Q000494:pharmacology*
D000959:Antihypertensive Agents; D015222:Sodium Channels; D014748:Vinca Alkaloids; C013983:vinpocetine; D014701:Veratridine; D014749:Vincamine