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)
|