Zuckerman A, Bolan E, de Paulis T, Schmidt D, Spector S, Pasternak G W
The Cotzias Laboratory of Neuro-Oncology, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Brain Res. 1999 Sep 18;842(1):1-5. doi: 10.1016/s0006-8993(99)01766-7.
Morphine-6-sulfate (M6S) and codeine-6-sulfate (C6S) are mu-selective opiates which have been isolated from brain. M6S is an effective analgesic, with a 30-fold greater potency than morphine in the mouse radiant heat tailflick assay and similar to the active morphine metabolite morphine-6beta-glucuronide (M6G). M6S analgesia is reversed by 3-methoxynaltrexone at low antagonist doses which are inactive against morphine, suggesting that M6S may be acting through the same mechanisms as M6G. Consistent with this possibility, antisense mapping of the MOR-1 clone revealed that M6S analgesia was lowered by probes targeting exon 2 and not by targeting exon 1, a sensitivity profile similar to that of M6G and not morphine. C6S also has analgesic activity at doses approximately 10-fold greater than M6S. However, its characterization was impeded by the appearance of seizures at doses below full analgesic activity. Thus, M6S is a potent analgesic with pharmacological properties similar to M6G. C6S has limited utility due to its high level of toxicity.
吗啡 - 6 - 硫酸盐（M6S）和可待因 - 6 - 硫酸盐（C6S）是已从大脑中分离出来的μ - 选择性阿片类药物。M6S是一种有效的镇痛药，在小鼠辐射热甩尾试验中其效力比吗啡高30倍，且与活性吗啡代谢物吗啡 - 6β - 葡萄糖醛酸苷（M6G）相似。低剂量的3 - 甲氧基纳曲酮可逆转M6S的镇痛作用，而该剂量对吗啡无拮抗作用，这表明M6S可能通过与M6G相同的机制发挥作用。与此可能性相符的是，对MOR - 1克隆进行反义图谱分析发现，靶向第2外显子的探针可降低M6S的镇痛作用，而靶向第1外显子的探针则无此作用，这种敏感性特征与M6G相似，与吗啡不同。C6S在剂量比M6S大约高10倍时也具有镇痛活性。然而，在低于完全镇痛活性的剂量下会出现癫痫发作，这妨碍了对其特性的研究。因此，M6S是一种强效镇痛药，其药理特性与M6G相似。由于C6S毒性水平高，其用途有限。
