Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
Department of Pharmacology, Institute of Health Sciences, Anadolu University, Eskişehir 26470, Turkey.
Molecules. 2021 May 28;26(11):3242. doi: 10.3390/molecules26113242.
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, ) 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 -chlorophenylalanine (serotonin-synthesis inhibitor), NAN-190 (serotonin 5-HT 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-HT serotonergic, α-adrenergic and opioidergic receptors, and contributions of central serotonergic and catecholaminergic neurotransmissions are critical for this effect.
文拉法辛是一种多模式抗抑郁药，影响多种脑神经化学物质，有可能对中枢神经系统产生各种药理作用。因此，我们研究了这种药物的中枢介导的镇痛功效及其作用机制。通过尾部夹、尾部浸入和热板试验来检查文拉法辛（5、10 和 20mg/kg）的镇痛活性。使用转棒装置评估动物的运动性能。时程测量（30-180min）表明，文拉法辛（10 和 20mg/kg）给药显著增加了所有伤害感受测试中的反应潜伏期、最大可能效应百分比和曲线下面积值。这些数据表明文拉法辛对携带急性热和机械伤害感受刺激的中枢途径具有镇痛作用。文拉法辛不改变小鼠的运动协调能力，表明该药物的镇痛活性是特异性的。在机制研究中，预先用-氯苯丙氨酸（血清素合成抑制剂）、NAN-190（5-羟色胺 5-HT 受体拮抗剂）、α-甲基-对酪氨酸（儿茶酚胺合成抑制剂）、苯氧胺（非选择性α-肾上腺素受体阻滞剂）和纳洛酮（非选择性阿片受体阻滞剂）预处理拮抗了文拉法辛引起的镇痛作用。研究结果表明，文拉法辛引起的镇痛作用是通过 5-HT 血清素能、α-肾上腺素能和阿片能受体介导的，中枢血清素能和儿茶酚胺能神经传递的贡献对这种作用至关重要。
