Non-competitive antagonism of N-methyl-D-aspartate receptor inhibits tolerance to the analgesic action of U-50,488H, a kappa-opiate receptor agonist in the rat.
Non-competitive antagonism of N-methyl-D-aspartate receptor inhibits tolerance to the analgesic action of U-50,488H, a kappa-opiate receptor agonist in the rat.
复制标题
N-甲基-D-天冬氨酸受体的非竞争性拮抗作用抑制大鼠对 U-50,488H（一种 κ 阿片受体激动剂）镇痛作用的耐受性。
DOI：
10.1016/0306-3623(94)00265-o
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Bhargava,HN
中科院分区：
文献类型：
--
作者：
Bhargava,HN
1. 研究了n-甲基- d -天冬氨酸（NMDA）受体非竞争性抑制剂二唑西平（MK-801）对高选择性阿片受体激动剂U-50,488 H的镇痛和降体温作用的影响。2. 通过连续4天每天两次腹腔注射U-50,488 H (25 mg/kg)，使雄性Sprague-Dawley大鼠对U-50,488 H的药理作用产生耐受。3. 多次注射U-50,488 H导致大鼠对其镇痛和降体温作用产生耐受。MK-801在每次注射U-50,488 H前10 min注射，剂量依赖性地抑制了对镇痛作用的耐受性，但对U-50,488 H的低温作用耐受性不受影响。4. 多次注射U-50,488 H可降低体增重。MK-801剂量依赖性地进一步减少体重增加。5. 结果表明，MK-801对NMDA受体的非竞争性拮抗作用可以选择性地抑制大鼠对U-50,488 H镇痛作用的耐受性，但这种作用与正常体重增加的显著降低有关。
1. The effect of dizocilpine (MK-801), a non-competitive inhibitor of N-methyl-D-aspartate (NMDA) receptor on the development of tolerance to the analgesic and hypothermic actions of U-50,488 H, a highly selective kappa-opiate receptor agonist, was determined in the rat. 2. Male Sprague-Dawley rats were made tolerant to the pharmacological actions of U-50,488 H by twice daily intraperitoneal (ip) injections of the drug (25 mg/kg) for 4 days. 3. Multiple injections of U-50,488 H resulted in the development of tolerance to its analgesic and hypothermic actions in the rat. MK-801 injected 10 min before each injection of U-50,488 H, dose-dependently inhibited the development of tolerance to the analgesic action but the tolerance to the hypothermic action of U-50,488 H was unaffected. 4. Multiple injections of U-50,488 H decreased the body weight gain. MK-801 dose-dependently decreased the gain in body weight further. 5. The results indicate that non-competitive antagonism of the NMDA receptor by MK-801 can selectively inhibit the tolerance to the analgesic action of U-50,488 H in the rat, however, such an effect was associated with significant decreases in normal gain in body weight.