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

Abstract

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.

• Authors: S A Erdo, P Molnár, V Lakics, J Z Bence, Z Tömösközi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 314 Issue 1-2 Pg. 69-73 (Oct 24 1996) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8957220 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antihypertensive Agents
• Sodium Channels
• Vinca Alkaloids
• vinpocetine
• Veratridine
• Vincamine

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Brain (drug effects, metabolism)
• Cell Death (drug effects)
• Cells, Cultured
• Ion Channel Gating (drug effects)
• Male
• Mice
• Patch-Clamp Techniques
• Rats
• Rats, Sprague-Dawley
• Sodium Channels (drug effects)
• Veratridine (antagonists & inhibitors, toxicity)
• Vinca Alkaloids (pharmacology)
• Vincamine (pharmacology)