Supraspinal mu 2-opioid receptors mediate spinal/supraspinal morphine synergy

Eur J Pharmacol. 1992 Sep 22;220(2-3):275-7. doi: 10.1016/0014-2999(92)90761-r.


TRIMU-5 (Tyr-D-Ala-Gly-NHC2H4CH(CH3)2) is a potent mu 2-opioid agonist/mu 1-opioid antagonist. A supraspinal dose (0.5 micrograms i.c.v.) of TRIMU-5 which is not analgesic when given alone antagonizes the analgesia produced by intracerebroventricular (i.c.v.) morphine, a mu 1 action. In contrast, in a synergy model consisting of the simultaneous administration of intrathecal morphine (0.1 micrograms) with multiple doses of i.c.v. morphine, the same supraspinal TRIMU-5 dose (0.5 micrograms 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 mu 1 receptors mediate supraspinal analgesia while mu 2 receptors mediate the synergy with spinal mu systems.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesia
  • Animals
  • Brain Stem / physiology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Injections, Intraventricular
  • Injections, Spinal
  • Male
  • Mice
  • Morphine / administration & dosage
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology*
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacology*
  • Receptors, Opioid, mu / physiology*


  • Oligopeptides
  • Receptors, Opioid, mu
  • Morphine
  • TRIMU 5