Christie M J, Vaughan C W, Ingram S L
Department of Pharmacology, University of Sydney, NSW, Australia.
Inflamm Res. 1999 Jan;48(1):1-4. doi: 10.1007/s000110050367.
We have established that mu-opioid receptor activation causes a presynaptic inhibition of neurotransmitter release that is mediated by 12-lipoxygenase metabolites of arachidonic acid in midbrain neurons [1]. We further demonstrated that the efficacy of opioids was enhanced synergistically by treatment of brain neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism; cyclooxygenase (COX-1) and 5-lipoxygenase. These findings explain a mechanism of analgesic action of NSAIDs in the central nervous system that is both independent of prostanoid release and inhibited by opioid antagonists, as well as the synergistic interaction of opioids with NSAIDs. These findings also suggest new avenues for development of centrally active medications involving combinations of lowered doses of opioids and specific 5-lipoxygenase inhibitors.
我们已经证实，μ-阿片受体激活会导致中脑神经元中神经递质释放的突触前抑制，这是由花生四烯酸的12-脂氧合酶代谢产物介导的[1]。我们进一步证明，通过用负责花生四烯酸代谢的其他主要酶（环氧化酶（COX-1）和5-脂氧合酶）的抑制剂处理脑神经元，阿片类药物的功效会协同增强。这些发现解释了非甾体抗炎药在中枢神经系统中的镇痛作用机制，该机制既独立于前列腺素释放，又受到阿片类拮抗剂的抑制，以及阿片类药物与非甾体抗炎药的协同相互作用。这些发现还为开发涉及低剂量阿片类药物和特定5-脂氧合酶抑制剂组合的中枢活性药物提供了新途径。
