Goucke Roger C, Hackett Peter L, Ilett Kenneth F
Department of Pain Management, Sir Charles Gairdner Hospital, Nedlands 6009 Australia Combined Unit in Clinical Pharmacology and Toxicology, State Health Laboratories/University of Western Australia, Nedlands 6009 Australia.
Pain. 1994 Feb;56(2):145-149. doi: 10.1016/0304-3959(94)90088-4.
Recent studies have suggested that morphine-3-glucuronide (M3G) may antagonize the analgesic effects of morphine and morphine-6-glucuronide (M6G). To investigate this hypothesis, steady-state concentrations of morphine, M6G and M3G in serum and cerebrospinal fluid (CSF) were measured in 11 patients receiving chronic morphine therapy (9 orally and 2 subcutaneously) for treatment of cancer-related pain. All patients appeared to have morphine-resistant pain and had elected to proceed to intrathecal bupivacaine or percutaneous cordotomy. Morphine, M6G and M3G concentrations were measured by high-performance liquid chromatography. The concentrations (median and range) for morphine, M6G and M3G in serum were 193 (14-1086) nmol/l, 847 (210-4113) nmol/l and 4553 (1324-24035) nmol/l, respectively, while in CSF concentrations of morphine, M6G and M3G were 200 (21-1461) nmol/l, 115 (30-427) nmol/l and 719 (249-3252) nmol/l, respectively. Median molar ratios of M6G/morphine and M3G/morphine in serum were 3.79 and 22.1, respectively, while in CSF the same ratios were 0.42 and 2.39, respectively. Median molar ratios of M3G/M6G in serum and CSF were 5.84 and 6.61, respectively. The median molar ratios for CSF/serum distribution of morphine, M6G and M3G were 1.23, 0.12 and 0.14, respectively. Thus, despite their relatively poor ability to penetrate into the CSF, the high serum concentrations of M6G and M3G resulted in substantial concentrations of these metabolites in the CSF. Nevertheless, M3G/M6G ratios in our morphine-resistant patients were similar to published values in patients with well-controlled pain, suggesting that the hypothesis that M3G plays a major role in morphine-resistance is not correct.
近期研究表明，吗啡-3-葡萄糖醛酸苷（M3G）可能会拮抗吗啡及吗啡-6-葡萄糖醛酸苷（M6G）的镇痛作用。为验证这一假说，对11例接受慢性吗啡治疗（9例口服，2例皮下注射）以缓解癌症相关疼痛的患者，测定了其血清和脑脊液（CSF）中吗啡、M6G及M3G的稳态浓度。所有患者似乎都存在吗啡抵抗性疼痛，且已选择进行鞘内布比卡因注射或经皮脊髓切开术。吗啡、M6G及M3G的浓度通过高效液相色谱法测定。血清中吗啡、M6G及M3G的浓度（中位数及范围）分别为193（14 - 1086）nmol/L、847（210 - 4113）nmol/L及4553（1324 - 24035）nmol/L，而脑脊液中吗啡、M6G及M3G的浓度分别为200（21 - 1461）nmol/L、115（30 - 427）nmol/L及719（249 - 3252）nmol/L。血清中M6G/吗啡及M3G/吗啡的摩尔比中位数分别为3.79和22.1，而在脑脊液中，相同的比值分别为0.42和2.39。血清和脑脊液中M3G/M6G的摩尔比中位数分别为5.84和6.61。吗啡、M6G及M3G的脑脊液/血清分布摩尔比中位数分别为1.23、0.12和0.14。因此，尽管M6G和M3G穿透进入脑脊液的能力相对较差，但血清中高浓度的M6G和M3G导致这些代谢产物在脑脊液中也有相当的浓度。然而，我们这些吗啡抵抗患者的M3G/M6G比值与疼痛控制良好患者的已发表值相似，这表明M3G在吗啡抵抗中起主要作用这一假说是不正确的。
