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Research ArticleNEUROPHARMACOLOGY

Vinpocetine Is a Potent Blocker of Rat NaV1.8 Tetrodotoxin-Resistant Sodium Channels

Xiaoping Zhou, Xiao-Wei Dong, James Crona, Maureen Maguire and Tony Priestley
Journal of Pharmacology and Experimental Therapeutics August 2003, 306 (2) 498-504; DOI: https://doi.org/10.1124/jpet.103.051086
Xiaoping Zhou
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Xiao-Wei Dong
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James Crona
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Maureen Maguire
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Tony Priestley
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Abstract

Vinpocetine is a clinically used synthetic vincamine derivative with a diverse pharmacological profile that includes action at several ion channels, principally “generic” populations of sodium channels that give rise to tetrodotoxin-sensitive conductances. A number of cell types are known to express tetrodotoxin-resistant (TTXr) sodium conductances, the molecular bases of which have remained elusive until recently. One such TTXr channel, termed NaV1.8, is of particular interest because of its prominent and selective expression in peripheral afferent nerves. The effects of vinpocetine on TTXr channels specifically, are unknown. We have assessed the effects of the drug on cloned rat NaV1.8 channels expressed in a dorsal root ganglion-derived cell line, ND7/23. Vinpocetine produced a concentration- and state-dependent inhibition of NaV1.8 sodium channel activity. Voltage-clamp experiments revealed an ∼3-fold increase in vinpocetine potency when whole-cell NaV1.8 conductances were elicited from relatively depolarized potentials (–35 mV; IC50 = 3.5 μM) compared with hyperpolarized holding potentials (–90 mV; IC50 = 10.4 μM). Vinpocetine also produced an ∼22 mV leftward shift in the voltage dependence of NaV1.8 channel inactivation but did not affect the voltage range of channel activation. These properties are reminiscent of several other known sodium channel blockers and suggested that vinpocetine may exhibit frequency-dependent block. Accordingly, tonic block of NaV1.8 channels by vinpocetine (3 μM) increased proportionally with increasing depolarizing commands over the frequency range 0.1 to 1Hz. In summary, the present data demonstrate that vinpocetine is capable of blocking NaV1.8 sodium channel activity and suggest a potential additional utility in various sensory abnormalities arising from abnormal peripheral nerve activity.

Footnotes

  • DOI: 10.1124/jpet.103.051086.

  • ABBREVIATIONS: TTX, tetrodotoxin; GFP, green fluorescent protein; DMEM, Dulbecco's modified Eagle's medium; TTXs, tetrodotoxin sensitive; TTXr, tetrodotoxin resistant, wt, wild-type.

    • Received February 28, 2003.
    • Accepted April 22, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 306 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 306, Issue 2
1 Aug 2003
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Research ArticleNEUROPHARMACOLOGY

Vinpocetine Is a Potent Blocker of Rat NaV1.8 Tetrodotoxin-Resistant Sodium Channels

Xiaoping Zhou, Xiao-Wei Dong, James Crona, Maureen Maguire and Tony Priestley
Journal of Pharmacology and Experimental Therapeutics August 1, 2003, 306 (2) 498-504; DOI: https://doi.org/10.1124/jpet.103.051086

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Research ArticleNEUROPHARMACOLOGY

Vinpocetine Is a Potent Blocker of Rat NaV1.8 Tetrodotoxin-Resistant Sodium Channels

Xiaoping Zhou, Xiao-Wei Dong, James Crona, Maureen Maguire and Tony Priestley
Journal of Pharmacology and Experimental Therapeutics August 1, 2003, 306 (2) 498-504; DOI: https://doi.org/10.1124/jpet.103.051086
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