Role of L-, N- and T-type Calcium Channels in Achieving Maximum Analgesic and Minimum Toxic Effect of Tramadol

M. Yilmaz, B. Suleyman, R. Mammadov, D. Altuner, T. Coban, S. Bulut, H. Suleyman, Resid Coskun
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Abstract

The aim of the study was to investigate the effects of lacidipine, amlodipine and benidipine on the analgesic activity and toxicity of tramadol. Rats (n=6/each group) were divided into five groups as control(CG), tramadol(TRD), lacidipine+tramadol(LTRD), amlodipine+tramadol(ATRD) and benidipine+tramadol(BTRD). Tramadol was administered once at a dose of 50 mg/kg and lacidipine, amlodipin, benidipin were administered at a dose of 4 mg/kg orally, once a day for 10 days. After the animals were sacrificed malondialdehyde(MDA) and total glutathione(tGSH) levels were measured in brain, heart, liver and kidney tissues. Troponin I(Tp I), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), and creatinine levels were determined in serum. Paw pain thresholds were measured 1 hour before and after drug administration. Analgesic effect of tramadol was increased the most by benidipine, while amlodipine and lacidipine increased it equally. Lacidipine failed to suppress MDA increase and tGSH decrease in brain tissue. Benidipine suppressed MDA increase and tGSH decrease in brain tissue better than amlodipine. All three drugs suppressed cardiac tissue oxidative stress and the release of TP I into the circulation. Lacidipine and amlodipine could not prevent tramadol-induced oxidative stress in liver and kidney tissues, whereas benidipine prevented excessive MDA increase and tGSH decrease. Benidipine significantly suppressed the increase of ALT, AST, BUN, and creatinine. Analgesic activity was 35.1% in TRD, 43.7% in LTRD 50.4% in ATRD and 67,5% in BTRD. Study results show that benidipine and tramadol co-treatment is better than co-treatment with lacidipine or amlodipine in achieving minimal toxic effects and maximum analgesia.
L、N 和 T 型钙通道在实现曲马多最大镇痛作用和最小毒性作用中的作用
该研究旨在探讨拉西地平、氨氯地平和贝尼地平对曲马多镇痛活性和毒性的影响。将大鼠(n=6/每组)分为对照组(CG)、曲马多组(TRD)、拉西地平+曲马多组(LTRD)、氨氯地平+曲马多组(ATRD)和贝尼地平+曲马多组(BTRD)五组。曲马多的剂量为 50 毫克/千克,拉西地平、氨氯地平和贝尼地平的剂量为 4 毫克/千克,每天口服一次,连续 10 天。动物被处死后,测量脑、心、肝和肾组织中丙二醛(MDA)和总谷胱甘肽(tGSH)的水平。测定血清中肌钙蛋白 I(Tp I)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血尿素氮(BUN)和肌酐水平。用药前后 1 小时测量爪痛阈值。贝尼地平对曲马多镇痛作用的增加最大,而氨氯地平和拉西地平对其镇痛作用的增加相同。拉西地平未能抑制脑组织中 MDA 的增加和 tGSH 的减少。与氨氯地平相比,贝尼地平能更好地抑制脑组织中 MDA 的增加和 tGSH 的减少。这三种药物都能抑制心脏组织的氧化应激和 TP I 在血液循环中的释放。拉西地平和氨氯地平不能阻止曲马多诱导的肝脏和肾脏组织氧化应激,而贝尼地平能阻止过量的 MDA 增加和 tGSH 减少。贝尼地平能明显抑制谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素氮(BUN)和肌酐(Creatinine)的升高。镇痛活性在 TRD 中为 35.1%,在 LTRD 中为 43.7%,在 ATRD 中为 50.4%,在 BTRD 中为 67.5%。研究结果表明,贝尼地平与曲马多联合治疗比与拉西地平或氨氯地平联合治疗更能达到最小的毒性反应和最大的镇痛效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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