5-HT1A Serotonergic, α-Adrenergic and Opioidergic Receptors Mediate the Analgesic Efficacy of Vortioxetine in Mice.

Nazlı Turan Yücel,Ümide Demir Özkay,Özgür Devrim Can,Ümmühan Kandemir

doi:10.3390/molecules26113242

Nazlı Turan Yücel, Ümide Demir Özkay + Show 2 more

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https://doi.org/10.3390/molecules26113242

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Abstract

Vortioxetine is a multimodal antidepressant drug that affects several brain neurochemicals and has the potential to induce various pharmacological effects on the central nervous system. Therefore, we investigated the centrally mediated analgesic efficacy of this drug and the mechanisms underlying this effect. Analgesic activity of vortioxetine (5, 10 and 20 mg/kg, p.o.) was examined by tail-clip, tail-immersion and hot-plate tests. Motor performance of animals was evaluated using Rota-rod device. Time course measurements (30–180 min) showed that vortioxetine (10 and 20 mg/kg) administrations significantly increased the response latency, percent maximum possible effect and area under the curve values in all of the nociceptive tests. These data pointed out the analgesic effect of vortioxetine on central pathways carrying acute thermal and mechanical nociceptive stimuli. Vortioxetine did not alter the motor coordination of mice indicating that the analgesic activity of this drug was specific. In mechanistic studies, pre-treatments with p-chlorophenylalanine (serotonin-synthesis inhibitor), NAN-190 (serotonin 5-HT1A receptor antagonist), α-methyl-para-tyrosine (catecholamine-synthesis inhibitor), phentolamine (non-selective α-adrenoceptor blocker), and naloxone (non-selective opioid receptor blocker) antagonised the vortioxetine-induced analgesia. Obtained findings indicated that vortioxetine-induced analgesia is mediated by 5-HT1A serotonergic, α-adrenergic and opioidergic receptors, and contributions of central serotonergic and catecholaminergic neurotransmissions are critical for this effect.

Highlights

Vortioxetine, an antidepressant drug, was licensed by the Food and Drug Administration (FDA) in September 2013 and the European Medicines Agency (EMA) in October2013
We investigated analgesic efficacy of disrupt vortioxetine based on its multimodal activity profile inthe thepotential
Findings of this research exhibited that vortioxetine exerts centrally mediated analgesic activity against acute mechanical and thermal nociceptive stimuli

Summary

Introduction

Vortioxetine, an antidepressant drug, was licensed by the Food and Drug Administration (FDA) in September 2013 and the European Medicines Agency (EMA) in October2013. Vortioxetine is a serotonergic modulator with antagonistic effects on serotonergic 5-HT3 , 5-HT7 , and 5-HT1D , agonistic effects on serotonergic 5-HT1A , and partial agonistic effects on serotonergic 5-HT1B receptor subtypes. It has a potent inhibitory effect on serotonin transporters [2]. The vortioxetine-induced increase in neurotransmitter levels is associated with the 5-HT3 receptor antagonistic and 5-HT1A agonistic activities of this drug because these receptors are involved in regulating neurotransmitter release in multiple brain regions [5]. In addition to the serotonergic and catecholaminergic systems, vortioxetine affects some other neurotransmitter systems in the brain This drug has been suggested to increase extracellular acetylcholine and histamine levels in the rat medial

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