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

Antiinflamm Antiallergy Agents Med Chem. 2024 Feb 21. doi: 10.2174/0118715230282982240202052127. Online ahead of print.

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.

Objective: 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 proinflammatory cytokine production. The compound also demonstrated safety at the cellular level.

Keywords: Tetrahydropyran derivative; antinociceptive effect; cytokines; inflammation.; mice; opioid system.