Bishnoi Mahendra, Patil Chandrashekar S, Kumar Anil, Kulkarni Shrinivas K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Chandigarh, India.
Indian J Exp Biol. 2006 Feb;44(2):128-32.
The present study was aimed to assess the combined effects of cyclooxygenase and 5-lipoxygenase (COX/5-LOX) inhibitors in different animal models of nociception. Naproxen, nimesulide and rofecoxib are well-established antinociceptive agents acting via COX inhibition. AKBA (acetyl-keto-beta-boswellic acid) is a 5-LOX inhibitor. AKBA (50-200 mg/kg) produced a dose dependent and significant antinociceptive effect in different animal models of nociception. Based on the earlier reports from our laboratory, sub effective doses of all the three COX Inhibitors were selected and they were administered (naproxen, 5 mg/kg; nimesulide, 1 mg/kg; and rofecoxib, 1 mg/kg) with AKBA (100 mg/kg). This produced a more significant antinociceptive effect as compared to per se effect observed in all the three models of nociception. However, the effect of combination of nimesulide with AKBA was more pronounced as compared to naproxen and rofecoxib and their combination with AKBA. The present finding provided an evidence for the potentiation of antinociceptive effect of NSAIDs with AKBA. Such a combination may help to reduce the therapeutic doses of conventional NSAIDs and also reduce side effects (gastric, cardiac and renal) that are popularly associated with the NSAIDs.
本研究旨在评估环氧化酶和5-脂氧合酶（COX/5-LOX）抑制剂在不同动物痛觉模型中的联合作用。萘普生、尼美舒利和罗非昔布是通过抑制COX发挥作用的成熟的抗痛觉药物。AKBA（乙酰基酮-β-乳香酸）是一种5-脂氧合酶抑制剂。AKBA（50-200毫克/千克）在不同动物痛觉模型中产生剂量依赖性且显著的抗痛觉作用。根据我们实验室早期的报告，选择了三种COX抑制剂的亚有效剂量，并将它们（萘普生，5毫克/千克；尼美舒利，1毫克/千克；罗非昔布，1毫克/千克）与AKBA（100毫克/千克）一起给药。与在所有三种痛觉模型中观察到的自身作用相比，这产生了更显著的抗痛觉作用。然而，与萘普生和罗非昔布及其与AKBA的组合相比，尼美舒利与AKBA组合的效果更明显。本研究结果为NSAIDs与AKBA联合增强抗痛觉作用提供了证据。这样的组合可能有助于降低传统NSAIDs的治疗剂量，并减少与NSAIDs普遍相关的副作用（胃部、心脏和肾脏方面的）。
