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柳氮磺胺吡啶:一种新型抗炎设计药物候选物。

Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

机构信息

Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil.

Pharmaceutic Chemical Laboratory, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil.

出版信息

Inflammation. 2018 Aug;41(4):1349-1360. doi: 10.1007/s10753-018-0783-x.

DOI:10.1007/s10753-018-0783-x
PMID:29654432
Abstract

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

摘要

柳胺酚是一种通过分子模拟和合理药物设计,由对乙酰氨基酚和水杨酸分子结合而成的新药。本研究旨在评估柳胺酚的急性口服毒性、镇痛和抗水肿作用。急性毒性试验依据 OECD 423 指南进行。在瑞士小鼠中,通过扭体、热板和福尔马林试验研究了镇痛作用。采用角叉菜胶诱导的足肿胀模型和蓖麻油诱导的 Wistar 大鼠皮炎评估抗水肿作用。在急性口服毒性评价过程中,柳胺酚未引起行为改变或动物死亡。此外,柳胺酚表现出外周镇痛活性,表现为扭体行为减少(ED50=4.95mg/kg)和福尔马林试验炎症期舔足时间延长。同时,柳胺酚在热板试验和福尔马林试验的神经源性期均表现出中枢镇痛活性。此外,柳胺酚对角叉菜胶或蓖麻油诱导的水肿形成具有抑制作用。总之,我们表明,柳胺酚作为一种新型 NSAID 候选药物,不会引起口服急性毒性,并具有外周镇痛作用(在扭体试验中比其前体强 10-25 倍)和抗水肿作用。柳胺酚还具有中枢镇痛活性,这似乎是通过阿片受体非依赖性机制介导的。这些发现表明柳胺酚是一种有前途的镇痛/抗水肿药物候选物。

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Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation.
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