Analgesic and Anti-inflammatory Potential of the New Tetrahydropyran Derivative (2s,6s)-6-ethyl-tetrahydro-2h-pyran-2-yl) Methanol.

Gustavo Nunes de Santana Castro, Raquel do Nascimento de Souza, Alba Cenélia Matos da Silva, Roberto Laureano-Melo, Wellington da Silva Côrtes, Saulo Luis Capim, Mário Luiz Araujo de Almeida Vasconcellos, Bruno Guimarães Marinho
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Abstract

Background: The development of analgesic and anti-inflammatory drugs plays a crucial role in modern medicine, aiming to alleviate pain and reduce inflammation in patients. Opioids and nonsteroidal anti-inflammatory drugs are groups of drugs conventionally used to treat pain and inflammation, but a wide range of adverse effects and ineffectiveness in some pathological conditions leads us to search for new drugs with analgesic and anti-inflammatory properties.

Objectives: In this regard, the authors intend to investigate the ((2s,6s)-6-ethyl-tetrahydro-2h-pyran- 2-yl) methanol compound (LS20) on pain and acute inflammation.

Methods: Male Swiss mice were evaluated using acetic acid-induced abdominal writhing, formalin, and tail-flick as models of nociceptive evaluation and edema paw, air pouch and cell culture as models of inflammatory evaluation besides the rotarod test for assessment of motor impairment.

Results: The compound showed an effect on the acetic acid-induced abdominal writhing, formalin and tail-flick tests. Studying the mechanism of action, reversion of the antinociceptive effect of the compound was observed from previous intraperitoneal administration of selective and non-selective opioid antagonists on the tail flick test. In addition, the compound induced an antiedematogenic effect and reduced leukocyte migration and the production of pro-inflammatory cytokines in the air pouch model. LS20 was able to maintain cell viability, in addition to reducing cell production of TNF-α and IL-6.

Conclusion: In summary, the LS20 compound presented an antinociceptive effect, demonstrating the participation of the opioid system and an anti-inflammatory effect related to the inhibition of pro-inflammatory cytokine production. The compound also demonstrated safety at the cellular level.

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新型四氢吡喃衍生物 (2s,6s)-6-ethyl-tetrahydro-2h-pyran-2-yl) 甲醇的镇痛和抗炎潜力。
背景:镇痛和抗炎药物的开发在现代医学中起着至关重要的作用,其目的是减轻患者的疼痛和炎症反应。阿片类药物和非甾体类抗炎药物是传统上用于治疗疼痛和炎症的药物类别,但它们的不良反应广泛,对某些病理情况无效,这促使我们寻找具有镇痛和抗炎特性的新药物:为此,作者打算研究((2s,6s)-6-乙基-四氢-2h-吡喃-2-基)甲醇化合物(LS20)对疼痛和急性炎症的影响:雄性瑞士小鼠以醋酸诱导的腹部蠕动、福尔马林和尾搔作为痛觉评估模型,以水肿爪、气囊和细胞培养作为炎症评估模型,并用转体试验评估运动障碍:结果:该化合物对醋酸诱导的腹部蠕动、福尔马林试验和尾搔试验均有影响。在研究其作用机制时,观察到该化合物的抗痛觉作用与之前腹腔注射选择性和非选择性阿片类拮抗剂对尾弹试验的抗痛觉作用发生了逆转。此外,在气囊模型中,该化合物还具有抗致畸作用,并能减少白细胞迁移和促炎细胞因子的产生。LS20 除了能减少细胞产生 TNF-α 和 IL-6 外,还能维持细胞活力:总之,LS20 复合物具有抗痛觉作用,表明阿片系统参与其中,并具有与抑制促炎细胞因子产生有关的抗炎作用。该化合物在细胞水平上也表现出安全性。
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