Department of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland.
Mini Rev Med Chem. 2013 Mar;13(3):335-52.
Numerous lines of evidence suggest that heterocyclic compounds used as analgesic, anti-inflammatory and anti-migraine agents can be potent regulators of the nitroxidative stress and targeting free nitrogen and oxygen radicals is a very promising strategy for future pain management. Both classical analgesics (nonsteroidal anti-inflammatory drugs, opioid drugs) and many analgesic adjuvants, including desipramine, duloxetine, fluoxetine, paroxetine, escitalopram, phenytoin or carbamazepine and α-lipoic acid can modulate the balance between pro-oxidant and antioxidant processes in the mammalian tissues and these properties of drugs such as indomethacin, meloxicam, tenoxicam, valdecoxib or some metabolites of analgesic drugs formed by the activity of tissue peroxidases may contribute to their clinical efficacy and drug-related toxic effects, including gastrointestinal ulcers, hepatic failure, agranulocytosis, aplastic anemia, neutropenia, opiate-induced hyperalgesia and tolerance. The antioxidant capacities of novel heterocyclic compounds, including the compounds acting either by prevention of formation or catalyzed decomposition of peroxynitrite anion (ONOO-), namely the peroxynitrite decomposition catalysts or as superoxide (O2 •-)-scavengers which are the functional mimetics of superoxide dismutase (SOD) enzymes (SODm), as well as the derivatives of 6-nitro-3,4-methylenedioxyphenyl-Nacylhydrazone (LASSBio-881) or γ-butyrolactone (LPP1, BM113, BM113A, BM138 and BM138A) are also discussed as potent and promising future heterocyclic analgesics.
大量证据表明，用作镇痛药、抗炎药和偏头痛治疗药物的杂环化合物可以有效调节氧化应激，靶向游离氮和氧自由基是未来疼痛管理的一个很有前途的策略。经典的镇痛药（非甾体抗炎药、阿片类药物）和许多镇痛药佐剂，包括去甲丙咪嗪、度洛西汀、氟西汀、帕罗西汀、依地普仑、苯妥英或卡马西平以及α-硫辛酸，都可以调节哺乳动物组织中促氧化剂和抗氧化剂之间的平衡，这些药物的特性，如吲哚美辛、美洛昔康、替诺昔康、伐地昔布或一些组织过氧化物酶活性形成的镇痛药代谢物，可能有助于它们的临床疗效和与药物相关的毒性作用，包括胃肠道溃疡、肝衰竭、粒细胞缺乏症、再生障碍性贫血、中性粒细胞减少症、阿片类药物引起的痛觉过敏和耐受。新型杂环化合物的抗氧化能力，包括通过预防过氧亚硝酸盐阴离子（ONOO-）的形成或催化其分解的化合物（过氧亚硝酸盐分解催化剂），或作为超氧化物（O2•-）清除剂的化合物，它们是超氧化物歧化酶（SOD）酶的功能模拟物（SODm），以及 6-硝基-3,4-亚甲二氧基苯基-N-酰基腙（LASSBio-881）或γ-丁内酯（LPP1、BM113、BM113A、BM138 和 BM138A）的衍生物，也被认为是有潜力和有前途的新型杂环类镇痛药。
