Hacısüleyman Levent, Saraç Bülent, Joha Ziad
Sivas Cumhuriyet University, Faculty of Medicine, Department of Pharmacology, Sivas, Türkiye.
Turk J Pharm Sci. 2022 Jun 27;19(3):336-342. doi: 10.4274/tjps.galenos.2021.41514.
Drugs that inhibit the reuptake of serotonin, norepinephrine, and/or dopamine are widely used for treating depressive disorders and have emerged as effective drugs for neuropathic pain. They have no substantial anti-nociceptive effects but are considered, with gabapentin/pregabalin, first-line drugs for neuropathic pain.
In this study, three different antidepressant agents were used in different doses to investigate their anti-hyperalgesic effects in rat models of neuropathic pain using hot plate and tail flick methods. They have different mechanisms of action; vilazodone hydrochloride is a selective serotonin inhibitor and a 5-HT partial agonist; talsupram hydrochloride is a selective noradrenaline inhibitor, and it has a high affinity for noradrenaline transporter (NET), whereas indatraline hydrochloride is a triple reuptake inhibitor that inhibits transporters for 5-HT (SERT), dopamine (DAT), and NET.
All the drugs used in the experiment were found to have an anti-hyperalgesic effect in both tests compared to the sham group. When anti-hyperalgesic effects of the three agents were compared to each other, it was found that talsupram hydrochloride was significantly more effective than the two other drugs in hot plate test. However, there was no statistically significant difference in the tail flick test. Indatraline hydrochloride was more effective than vilazodone hydrochloride at the same doses in the tail flick test.
Our data suggest that three drugs are effective analgesics in rat models of neuropathic pain and inhibition of noradrenaline reuptake represents the cornerstone of analgesic mechanisms of effective antidepressants.
抑制5-羟色胺、去甲肾上腺素和/或多巴胺再摄取的药物被广泛用于治疗抑郁症,并且已成为治疗神经性疼痛的有效药物。它们没有实质性的抗伤害感受作用,但与加巴喷丁/普瑞巴林一起被视为神经性疼痛的一线药物。
在本研究中,使用三种不同剂量的抗抑郁药,通过热板法和甩尾法,研究它们在神经性疼痛大鼠模型中的抗痛觉过敏作用。它们具有不同的作用机制;盐酸维拉唑酮是一种选择性5-羟色胺抑制剂和5-羟色胺部分激动剂;盐酸他索普明是一种选择性去甲肾上腺素抑制剂,对去甲肾上腺素转运体(NET)具有高亲和力,而盐酸茚达曲林是一种三重再摄取抑制剂,可抑制5-羟色胺(SERT)、多巴胺(DAT)和NET的转运体。
与假手术组相比,实验中使用的所有药物在两种测试中均具有抗痛觉过敏作用。当比较三种药物的抗痛觉过敏作用时,发现盐酸他索普明在热板试验中比其他两种药物明显更有效。然而,在甩尾试验中没有统计学上的显著差异。在甩尾试验中,相同剂量下盐酸茚达曲林比盐酸维拉唑酮更有效。
我们的数据表明,三种药物在神经性疼痛大鼠模型中是有效的镇痛药,抑制去甲肾上腺素再摄取是有效抗抑郁药镇痛机制的基石。