4-Methylbenzocarbothioamide 是一种硫化氢供体，可抑制肿瘤坏死因子-α 和 CXCL1 的产生，并在疼痛和炎症模型中表现出活性。,European Journal of Pharmacology

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4-Methylbenzocarbothioamide 是一种硫化氢供体，可抑制肿瘤坏死因子-α 和 CXCL1 的产生，并在疼痛和炎症模型中表现出活性。
European Journal of Pharmacology ( IF 4.2 ) Pub Date : 2019-05-24 , DOI: 10.1016/j.ejphar.2019.172404
Ivo S F Melo ₁ , Felipe F Rodrigues ₁ , Sarah O A M Costa ₁ , Alysson Vinícius Braga ₁ , Marcela Ísis Morais ₁ , Jéssica A Vaz ₁ , Leonardo S Neto ₂ , Izabela Galvão ₃ , Luzia V Modolo ₄ , Flávio A Amaral ₃ , Renata B Oliveira ₁ , Ângelo de Fátima ₂ , Márcio M Coelho ₁ , Renes R Machado ₁

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已知气体传输剂硫化氢 (H2S) 可调节许多病理生理过程。临床前试验表明 H2S 供体具有抗炎和镇痛活性，其特征是减少炎症介质的产生、白细胞募集、水肿和机械性异常性疼痛。在本研究中，评估了 4-甲基苯硫代酰胺 (4-MBC) 在小鼠疼痛和炎症模型中的作用、介导这些作用的机制以及该化合物的 H2S 释放特性。在没有有机硫醇的情况下，4-MBC 在体外自发释放 H2S。腹膜内 (ip) 施用 4-MBC（100 或 150 mg/kg）可减少由甲醛诱导的第二阶段伤害性反应，并诱导对角叉菜胶机械性异常性疼痛的长期抑制作用。4-MBC 抗异常性疼痛作用不受先前给予纳曲酮或格列本脲的影响。4-MBC（50、100 或 150 mg/kg，腹腔注射）对角叉菜胶引起的爪水肿具有持久的抑制作用。4-MBC 的最高剂量 (150 mg/kg, ip) 抑制了角叉菜胶诱导的肿瘤坏死因子-α 和 CXCL1 的产生以及髓过氧化物酶的活性。由角叉菜胶引起的机械性异常性疼痛和爪子水肿不受 4-MBC 氧代类似物（对甲苯甲酰胺）的抑制。总之，4-MBC 是一种释放 H2S 的硫代苯甲酰胺，具有镇痛和抗炎活性。这些活动可能是由于细胞因子和趋化因子的产生和中性粒细胞募集减少。H2S 释放特性可能对 4-MBC 活动至关重要。

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4-Methylbenzenecarbothioamide, a hydrogen sulfide donor, inhibits tumor necrosis factor-α and CXCL1 production and exhibits activity in models of pain and inflammation.

The gasotransmitter hydrogen sulfide (H2S) is known to regulate many pathophysiological processes. Preclinical assays have demonstrated that H2S donors exhibit anti-inflammatory and antinociceptive activities, characterized by reduction of inflammatory mediators production, leukocytes recruitment, edema and mechanical allodynia. In the present study, the effects induced by 4-methylbenzenecarbothioamide (4-MBC) in models of pain and inflammation in mice, the mechanisms mediating such effects and the H2S-releasing property of this compound were evaluated. 4-MBC spontaneously released H2S in vitro in the absence of organic thiols. Intraperitoneal (i.p.) administration of 4-MBC (100 or 150 mg/kg) reduced the second phase of the nociceptive response induced by formaldehyde and induced a long lasting inhibitory effect on carrageenan mechanical allodynia. 4-MBC antiallodynic effect was not affected by previous administration of naltrexone or glibenclamide. 4-MBC (50, 100 or 150 mg/kg, i.p.) induced a long lasting inhibitory effect on paw edema induced by carrageenan. The highest dose (150 mg/kg, i.p.) of 4-MBC inhibited tumor necrosis factor-α and CXCL1 production and myeloperoxidase activity induced by carrageenan. Mechanical allodynia and paw edema induced by carrageenan were not inhibited by the 4-MBC oxo analogue (p-toluamide). In summary, 4-MBC, an H2S releasing thiobenzamide, exhibits antinociceptive and anti-inflammatory activities. These activities may be due to reduced cytokine and chemokine production and neutrophil recruitment. The H2S releasing property is likely essential for 4-MBC activity. Our results indicate that 4-MBC may represent a useful pharmacological tool to investigate the biological roles of H2S.

更新日期：2019-11-01

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