Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Neurobiotechnology Research Group, Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center for Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), Pelotas, RS, 96010-900, Brazil.
Nucleus of Synthesis, Application, and Analysis of Organic and Inorganic Compounds (NUSAACOI), Federal University of Fronteira Sul (UFFS), Cerro Largo, RS, Brazil.
Chem Biol Interact. 2022 May 25;359:109918. doi: 10.1016/j.cbi.2022.109918. Epub 2022 Mar 26.
Pain strongly affects public health, both because of the patient suffering and the socioeconomic impact. The available drugs for pain treatment are not fully effective and have many adverse effects. Therefore, there is a need to obtain new analgesic compounds. This study evaluated the antinociceptive effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), an organoselenium compound containing the benzamide moiety, through time (15-120 min) and dose-response (1-50 mg/kg) curves in thermal and chemical mice models of nociception, as well as the involvement of the serotonergic system in this effect. The open-field test (OFT) was carried out to assess locomotor activity. SePB (10 mg/kg) induced an increase in the latency to nociception response in the tail immersion test from 30 min. In the dose-response curves, SePB at different doses reduced latency time to nociceptive response in the tail immersion and hot plate tests, and reduced the licking time in the glutamate test, demonstrating antinociceptive effect, without altering the locomotor activity of mice. WAY100635 (0.5 mg/kg, subcutaneously, a 5-HT receptor antagonist), ketanserin (0.3 mg/kg, intraperitoneally, a 5-HT receptor antagonist), but not ondansetron (0.5 mg/kg, intraperitoneally, a 5-HT receptor antagonist), administered 15 min before SePB, prevented the increased latency to nociceptive response induced by SePB in the tail immersion test, demonstrating that 5-HT and 5-HT receptors are involved in the antinociceptive effect of SePB. Upon more studies evaluating SePB antinociceptive effects in chronic pain models and its toxicity, this compound could be indicated as an interesting molecule to treat pain.
疼痛强烈影响公众健康，不仅因为患者的痛苦，还因为其对社会经济的影响。现有的疼痛治疗药物并非完全有效，且具有许多不良反应。因此，有必要获得新的镇痛化合物。本研究通过热和化学刺激诱导的疼痛模型（时间和剂量-反应）曲线，以及 5-羟色胺系统在该效应中的参与，评估了含有苯甲酰胺部分的有机硒化合物 N-(3-(苯硒基)丙-2-炔-1-基)苯甲酰胺 (SePB) 的镇痛作用。旷场试验 (OFT) 用于评估运动活性。SePB（10mg/kg）在尾浸入试验中使疼痛反应潜伏期从 30 分钟开始增加。在剂量-反应曲线中，不同剂量的 SePB 缩短了尾浸入和热板试验中疼痛反应的潜伏期时间，并减少了谷氨酸试验中的舔舐时间，表明具有镇痛作用，而不改变小鼠的运动活性。WAY100635（0.5mg/kg，皮下注射，5-HT 受体拮抗剂）、酮色林（0.3mg/kg，腹腔注射，5-HT 受体拮抗剂），但不是昂丹司琼（0.5mg/kg，腹腔注射，5-HT 受体拮抗剂），在 SePB 给药前 15 分钟给药，可防止 SePB 在尾浸入试验中引起的疼痛反应潜伏期增加，表明 5-HT 和 5-HT 受体参与了 SePB 的镇痛作用。在更多的研究评估了 SePB 在慢性疼痛模型中的镇痛作用及其毒性后，这种化合物可能被认为是一种治疗疼痛的有趣分子。
