Differences in the antinociceptive effects of serotonin–noradrenaline reuptake inhibitors via sodium channel blockade using the veratrine test in mice

Abstract

Antidepressants exert their analgesic effects by inhibiting the reuptake of noradrenaline. Several antidepressants have been shown to block the sodium channels, which might contribute to their analgesic potency. The aim of this study was to determine whether serotonin-noradrenaline reuptake inhibitors (SNRIs) could produce antinociceptive effects via sodium channel blockade using the veratrine test in mice. Furthermore, the effects of these agents on the veratrine test were examined to elucidate the effects of several antidepressants and tramadol on sodium channels. The administration of duloxetine (10 mg/kg) and venlafaxine (30 mg/kg) suppressed cuff-induced mechanical allodynia; however, these antinociceptive effects were only partially suppressed by atipamezole. Furthermore, duloxetine and venlafaxine demonstrated antinociceptive effects via sodium channel blockade, as assayed by the veratrine test. In addition, several antidepressants, including amitriptyline, paroxetine and mirtazapine, reduced veratrine-induced nociception.In contrast, milnacipran and tramadol did not alter the veratrine-induced nociception. These results indicated that, in addition to the primary action of SNRIs on monoamine transporters, sodium channel blockade might be involved in the antinociceptive activities of duloxetine and venlafaxine, but not milnacipran.

Fentanyl Analogs Exert Antinociceptive Effects <i>via</i> Sodium Channel Blockade in Mice

“…These types of behaviors, such as licking, biting, and scratching, were similar to those observed with injections of formalin, 10) and glutamate 7) in mice. We have shown that not only the sodium channel blockers mexiletine and carbamazepine 9) but also the antidepressants with the potential to inhibit sodium channels duloxetine and venlafaxine 11) suppressed veratrine-induced nociceptive responses. However, the calcium channel alpha-2-delta subunit ligands gabapentin and the T-type calcium channel blocker ethosuximide did not affect veratrine-induced nociception.…”

Systemic and Brain Pharmacokinetics of Milnacipran in Mice: Comparison of Intraperitoneal and Intravenous Administration

“…While milnacipran continues to be an active subject of experimental and clinical studies focusing on chronic pain and major depression [ 9 , 10 , 11 ], it is also being evaluated for other disorders, including cognitive impairment after traumatic brain injury [ 12 ], apnea during Rett syndrome [ 13 ], attention-deficit/hyperactivity disorder [ 14 ] and autism spectrum disorder [ 15 ]. Curiously, there is a paucity of published studies reporting systemic and brain pharmacokinetics of milnacipran in rodents.…”