SUPRASPINAL MU-2-OPIOID RECEPTORS MEDIATE SPINAL SUPRASPINAL MORPHINE SYNERGY

被引:22
作者
PICK, CG
ROQUES, B
GACEL, G
PASTERNAK, GW
机构
[1] MEM SLOAN KETTERING CANC CTR,COTZIAS LAB NEUROONCOL,1275 YORK AVE,NEW YORK,NY 10021
[2] CNRS,INSERM,CHIM ORGAN LAB,F-75270 PARIS 06,FRANCE
[3] CORNELL UNIV,MED CTR,COLL MED,DEPT NEUROL,NEW YORK,NY 10021
[4] CORNELL UNIV,MED CTR,COLL MED,DEPT NEUROSCI,NEW YORK,NY 10021
[5] CORNELL UNIV,MED CTR,COLL MED,DEPT PHARMACOL,NEW YORK,NY 10021
关键词
MORPHINE; ANALGESIA; MU-OPIOID RECEPTORS;
D O I
10.1016/0014-2999(92)90761-R
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
TRIMU-5 (Tyr-D-Ala-Gly-NHC2H4CH(CH3)2) is a potent mu2-opioid agonist/mu1-opioid antagonist. A supraspinal dose (0.5 mug i.c.v.) of TRIMU-5 which is not analgesic when given alone antagonizes the analgesia produced by intracerebroventricular (i.c.v.) morphine, a mu1 action. In contrast, in a synergy model consisting of the simultaneous administration of intrathecal morphine (0.1 mug) with multiple doses of i.c.v. morphine, the same supraspinal TRIMU-5 dose (0.5 mug i.c.v.) enhances analgesia. Supraspinal TRIMU-5 also potentiates spinal morphine directly, shifting its dose-response to the left. These results imply that within the brainstem mu1 receptors mediate supraspinal analgesia while mu2 receptors mediate the synergy with spinal mu systems.
引用
收藏
页码:275 / 277
页数:3
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