Differential Modulation of Nav1.7 and Nav1.8 channels by antidepressant drugs.

Differential Modulation of Nav1.7 and Nav1.8 channels by antidepressant drugs. Eur J Pharmacol. 2015 Jul 14; Authors: Thériault O, Poulin H, Beaulieu JM, Chahine M Abstract Antidepressant drugs of the SSRI family are used as a third-line treatment for neuropathic pain. In contrast MAOi antidepressants, that also increase extracellular serotonin bioavailability have little or no effects on this condition. In addition to their action of the serotonin transporter, some SSRI have been shown to inhibit voltage gated sodium channels. Here we investigated the potential inhibition of SSRIs and MAOi antidepressants on Nav1.7 or Nav1.8, which are expressed in sensory neurons and play an important role in pain sensation. We used the whole-cell patch-clamp technique on HEK293 cells expressing either Nav1.7 or Nav1.8, and evaluated the effects of the SSRIs fluoxetine, paroxetine, and citalopram as well as one MAOi antidepressants on the electrophysiological properties of the Na(+) channels. Paroxetine exhibited the greatest affinity for Na(+) channels. In ascending order of affinity for Nav1.7 were paroxetine (IC50=10µM), followed by fluoxetine (IC50=66µM), then citalopram (IC50=174µM). In ascending order of affinity for Nav1.8 were paroxetine (IC50=9µM), followed by fluoxetine (IC50=49µM), then citalopram (IC50=100µM). Paroxetine and fluoxetine accelerated the onset of slow-inactivation and delayed the time-course of recovery from inactiv...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research