The Role of Sodium Channels in the Mechanism of Action of Antidepressants and Mood Stabilizers

Author(s): Michel Bourin, Franck Chenu, Martine Hascoet

Journal Name: Current Drug Targets

Volume 10 , Issue 11 , 2009


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Abstract:

Antidepressant drugs modify in different ways the activity of neurons, by increasing monoamines levels and by modulating ion channels. Sodium channels are molecular targets for antiepileptic drugs, which can also be mood stabilizers (i.e. lamotrigine, topiramate, phenytoin, carbamazepine, valproic acid). After a short overview on the sodium channels and the interaction with antidepressants and mood stabilizers, a comparison of the activity of both antidepressants and mood stabilizers with the addition of veratrine (sodium channel opener) on the forced swimming test (FST) in mice was presented. By comparing the antidepressant-like effect of the antidepressants (paroxetine, imipramine and desipramine) with the one of anticonvulsants (lamotrigine, phenytoin and topiramate) on the FST, it seems that the mechanism of action of anticonvulsants and antidepressants is different, because veratrine limits the activity of anticonvulsants but not of antidepressants. The anticonvulsants topiramate and phenytoin reduce the immobility time in the FST in a range of time similar to that induced by antidepressants, suggesting that the FST could be sensitive to both drugs. The magnitude of antidepressant- like effect of the lamotrigine (acting through an increase in monoaminergic neurotransmission and a blockade of sodium channels) in the FST is greater than what is obtained after administration of the other drugs, suggesting that this dual activity could be used as an augmentation strategy. Authors conclude that the development of new drugs acting on sodium channels could potentially be of interest as antidepressants, but also as augmentation strategies for classical antidepressants.

Keywords: Forced swim test (FST)

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Article Details

VOLUME: 10
ISSUE: 11
Year: 2009
Page: [1052 - 1060]
Pages: 9
DOI: 10.2174/138945009789735138
Price: $65

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