McCarthy Robert J, Kroin Jeffrey S, Lubenow Timothy R, Penn Richard D, Ivankovich Anthony D
Dept. of Anesthesiology, Rush Medical College, Chicago, IL 60612 U.S.A. Dept. of Neurosurgery, Rush Medical College, Chicago, IL 60612 U.S.A.
Pain. 1990 Mar;40(3):333-338. doi: 10.1016/0304-3959(90)91130-B.
Experiments were performed in rats to determine if the alpha 2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure. Rats were chronically implanted with catheters in the lumbar subarachnoid space. Antinociception was evaluated in conscious rats with the tail-flick test. Increasing tizanidine doses produced increases in analgesic efficacy, with 25 micrograms producing a significant long-lasting antinociception. This tail-flick analgesia was very similar to that produced by clonidine (25 micrograms) and morphine (8 micrograms) in peak effect and duration. Doses as high as 250 micrograms produced only a transient hind limb motor dysfunction in 43% of the animals. Daily injections of 25 micrograms tizanidine over 5 days produced a decrease in antinociception, with the peak effect at day 5 at 59% of that at day 1. Blood pressure, in rats lightly anesthetized with halothane, was not affected by tizanidine injections up to 250 micrograms. Tizanidine appears to be a promising non-opiate analgesic for intrathecal usage.
在大鼠身上进行了实验，以确定α2-肾上腺素能激动剂替扎尼定鞘内注射时是否具有抗伤害感受作用，以及这种镇痛作用是否伴随着血压变化。大鼠被长期植入腰蛛网膜下腔导管。采用甩尾试验对清醒大鼠的抗伤害感受进行评估。增加替扎尼定剂量可提高镇痛效果，25微克时可产生显著的长效抗伤害感受作用。这种甩尾镇痛在峰值效应和持续时间上与可乐定（25微克）和吗啡（8微克）产生的镇痛非常相似。高达250微克的剂量仅在43%的动物中产生短暂的后肢运动功能障碍。连续5天每天注射25微克替扎尼定导致抗伤害感受作用降低，第5天的峰值效应为第1天的59%。在轻度氟烷麻醉的大鼠中，注射高达250微克的替扎尼定对血压没有影响。替扎尼定似乎是一种有前景的用于鞘内给药的非阿片类镇痛药。
