Toljan Karlo, Vrooman Bruce
Department of Pathophysiology, University of Zagreb School of Medicine, Kispaticeva 12, 10 000 Zagreb, Croatia.
Section of Pain Medicine, Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03756, USA.
Med Sci (Basel). 2018 Sep 21;6(4):82. doi: 10.3390/medsci6040082.
Naltrexone and naloxone are classical opioid antagonists. In substantially lower than standard doses, they exert different pharmacodynamics. Low-dose naltrexone (LDN), considered in a daily dose of 1 to 5 mg, has been shown to reduce glial inflammatory response by modulating Toll-like receptor 4 signaling in addition to systemically upregulating endogenous opioid signaling by transient opioid-receptor blockade. Clinical reports of LDN have demonstrated possible benefits in diseases such as fibromyalgia, Crohn's disease, multiple sclerosis, complex-regional pain syndrome, Hailey-Hailey disease, and cancer. In a dosing range at less than 1 μg per day, oral naltrexone or intravenous naloxone potentiate opioid analgesia by acting on filamin A, a scaffolding protein involved in μ-opioid receptor signaling. This dose is termed ultra low-dose naltrexone/naloxone (ULDN). It has been of use in postoperative control of analgesia by reducing the need for the total amount of opioids following surgery, as well as ameliorating certain side-effects of opioid-related treatment. A dosing range between 1 μg and 1 mg comprises very low-dose naltrexone (VLDN), which has primarily been used as an experimental adjunct treatment for boosting tolerability of opioid-weaning methadone taper. In general, all of the low-dose features regarding naltrexone and naloxone have been only recently and still scarcely scientifically evaluated. This review aims to present an overview of the current knowledge on these topics and summarize the key findings published in peer-review sources. The existing potential of LDN, VLDN, and ULDN for various areas of biomedicine has still not been thoroughly and comprehensively addressed.
纳曲酮和纳洛酮是经典的阿片类拮抗剂。在远低于标准剂量时，它们具有不同的药效学作用。低剂量纳曲酮（LDN），每日剂量为1至5毫克，已被证明除了通过短暂阻断阿片受体系统上调内源性阿片信号外，还可通过调节Toll样受体4信号来减少胶质细胞炎症反应。LDN的临床报告表明，它在纤维肌痛、克罗恩病、多发性硬化症、复杂性区域疼痛综合征、黑利-黑利病和癌症等疾病中可能具有益处。在每天低于1微克的剂量范围内，口服纳曲酮或静脉注射纳洛酮通过作用于细丝蛋白A（一种参与μ阿片受体信号传导的支架蛋白）来增强阿片类镇痛作用。这个剂量被称为超低剂量纳曲酮/纳洛酮（ULDN）。它已被用于术后镇痛控制，减少术后阿片类药物的总量需求，并改善阿片类相关治疗的某些副作用。1微克至1毫克的剂量范围包括极低剂量纳曲酮（VLDN），其主要用作增强阿片类药物脱毒美沙酮逐渐减量耐受性的实验性辅助治疗。一般来说，关于纳曲酮和纳洛酮的所有低剂量特性直到最近才得到科学评估，而且仍然很少。本综述旨在概述这些主题的当前知识，并总结同行评审来源中发表的关键发现。LDN、VLDN和ULDN在生物医学各个领域的现有潜力仍未得到全面和深入的探讨。
