Vortioksetin'in antinosiseptif etkinliğinin ve altta yatan olası mekanizmaların değerlendirilmesi

Vortioxetine is a relatively new antidepressant with a multimodal mechanism of action. The mechanism of antidepressant action of this drug is not known, but it is thought to be related to direct modulation of serotonergic receptor activity and inhibition of serotonin transporter. The antinociceptive efficacy of vortioxetine was investigated in this study based on the knowledge that drugs that enhance monoaminergic neurotransmission in the central nervous system have potential for analgesic activity. The antinociceptive efficacy of vortioxetine was evaluated by tail-clip and hot-plate tests. The findings showed that the drug, at doses of 5 and 10 mg/kg, has central antinociceptive activity in mice, against mechanical and thermal nociceptive stimuli induced acute pain. Naloxone, a non-selective opioid receptor antagonist, p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, and alpha-methyl-para-tyrosine (AMPT), an inhibitor of catecholamine synthesis were used to elucidate the possible involvement of opiodergic, serotonergic and catecholaminergic mechanisms to the mentioned antinociceptive effect of vortioxetine, respectively. Data from the mechanistic studies indicated that naloxone, PCPA and AMPT pre-treatments abolished the acute antinociceptive effect induced by 5 mg/kg dose of vortioxetine. Based on these findings, it was concluded that the acute antinociceptive activity of vortioxetine was mediated by opioidergic, serotonergic and catecholaminergic systems. Comprehensive studies with specific receptor subtype blockers are needed to fully elucidate the antinociceptive mechanism of action of vortioxetine.