A novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline inhibits nociception and oedema in mice
A novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline inhibits nociception and oedema in mice
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DOI：
10.1038/bjp.2008.303
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发表时间：
2008-11-01
影响因子：
7.3
通讯作者：
Coelho, M. M.
中科院分区：
文献类型：
--
作者：
Bastos, L. F. S.;Angusti, A.;Coelho, M. M.
背景和目的：许多体外研究和较少的体内研究表明四环素类药物具有抗炎活性。我们研究了一种新的非抗菌，非螯合羟基吡唑啉衍生物的米诺环素，12 S-羟基-1，12-吡唑啉米诺环素（PMIN），也诱导抗伤害和抗炎作用。实验方法：对米诺环素敏感的金黄色葡萄球菌菌株的抗菌作用进行了评估，通过应用圆筒板琼脂扩散技术。还评价了来自用米诺环素或PMIN预处理的小鼠的稀释血清的抗菌效果。用分光光度法测定Ca 2+结合活性。在小鼠中评价福尔马林诱导的伤害性反应和角叉菜胶诱导的爪水肿。旋转杆装置被用来评估运动coordination.Key结果：米诺环素，而不是PMIN，抑制细菌的生长。用二甲胺四环素处理而不用PMIN处理的小鼠的血清也诱导了这种效应。二甲胺四环素溶液的紫外吸收光谱，但不是那些PMIN，显着改变的Ca 2+的存在下。米诺环素或PMIN抑制福尔马林诱导的伤害性感受和角叉菜胶诱导的爪水肿的两个阶段。这是不太可能的，antinociception导致缺乏运动协调，四环素没有损害小鼠的性能上的旋转road.Conclusions和影响：这些结果表明，抑制伤害性和水肿四环素类既不一定与抗菌也不钙螯合活性。这项研究支持评估PMIN在治疗疼痛和炎症性疾病中的潜在有用性，因为其缺乏抗菌和Ca 2+螯合活性可能比传统四环素类药物具有更大的安全性。
Background and purpose: Many in vitro and fewer in vivo studies have shown that tetracyclines present anti-inflammatory activity. We investigated if a novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline, 12S-hydroxy-1,12- pyrazolinominocycline (PMIN), also induced antinociceptive and anti-inflammatory effects.Experimental approach: Antibacterial effects against a minocycline-sensitive Staphylococcus aureus strain were evaluated by applying a cylinder-plate agar diffusion technique. Antibacterial effects of diluted serum from mice pre-treated with minocycline or PMIN were also evaluated. Ca2+ binding activity was assessed by spectrophotometry. Formalin-induced nociceptive responses and carrageenan-induced paw oedema were evaluated in mice. The rota-rod apparatus was used to evaluate motor coordination.Key results: Minocycline, but not PMIN, inhibited bacterial growth. Serum from mice treated with minocycline, but not with PMIN, also induced such an effect. The UV absorption spectrum of solutions of minocycline, but not those of PMIN, was markedly changed in the presence of Ca2+. Minocycline or PMIN inhibited both phases of formalin-induced nociception and carrageenan-induced paw oedema. It is unlikely that antinociception resulted from lack of motor coordination, as tetracycline did not impair the performance of mice on the rotating rod.Conclusions and implications: These results indicate that inhibition of nociception and oedema by tetracyclines is neither necessarily linked to antibacterial nor to Ca2+ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the treatment of painful and inflammatory diseases, as its lack of antibacterial and Ca2+ chelating activities might confer greater safety over conventional tetracyclines.