Srinivasan V, Wielbo D, Simpkins J, Karlix J, Sloan K, Tebbett I
Department of Pharmaceutics, University of Florida, Gainesville 32610, USA.
Pharm Res. 1996 Feb;13(2):296-300. doi: 10.1023/a:1016059618633.
The antinociceptive and immunosuppressive effects of codeine and codeine 6-glucuronide were determined in rats after intracerebroventricular administration.
Codeine 6-glucuronide was synthesized using a modification of the Koenigs-Knorr reaction. A lipophilic intermediate formed during synthesis, methyl [codein-6-yl-2,3,4-tri-O-acetyl-beta-D-glucopyranosid] uronate, was also tested. Morphine was used as a positive control to compare antinociceptive potencies of these compounds.
All compounds tested produced significant analgesic responses, as assessed by the tail flick model. Additionally, codeine 6-glucuronide showed significantly less immunosuppressive effects than codeine in vitro.
We conclude that codeine 6-glucuronide and related compounds may have clinical benefit in the treatment of pain in immune compromised patients.
测定脑室内注射后可待因和可待因6-葡萄糖醛酸苷在大鼠体内的抗伤害感受和免疫抑制作用。
采用改进的柯尼希斯-克诺尔反应合成可待因6-葡萄糖醛酸苷。合成过程中形成的亲脂性中间体，即[可待因-6-基-2,3,4-三-O-乙酰基-β-D-吡喃葡萄糖苷]尿酸甲酯，也进行了测试。吗啡用作阳性对照，以比较这些化合物的抗伤害感受效力。
通过甩尾模型评估，所有测试化合物均产生显著的镇痛反应。此外，可待因6-葡萄糖醛酸苷在体外显示出比可待因明显更少的免疫抑制作用。
我们得出结论，可待因6-葡萄糖醛酸苷及相关化合物可能对免疫功能受损患者的疼痛治疗具有临床益处。
