Pick C G, Roques B, Gacel G, Pasternak G W
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
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.
TRIMU-5（酪氨酰-D-丙氨酰-甘氨酰-NHC2H4CH(CH3)2）是一种强效的μ2阿片受体激动剂/μ1阿片受体拮抗剂。单独给药时无镇痛作用的脊髓上剂量（0.5微克，脑室内注射）的TRIMU-5可拮抗脑室内（i.c.v.）吗啡产生的镇痛作用，这是一种μ1作用。相比之下，在由鞘内注射吗啡（0.1微克）与多剂量脑室内吗啡同时给药组成的协同模型中，相同的脊髓上TRIMU-5剂量（0.5微克，脑室内注射）可增强镇痛作用。脊髓上的TRIMU-5还可直接增强脊髓吗啡的作用，使其剂量反应向左移动。这些结果表明，在脑干内，μ1受体介导脊髓上镇痛，而μ2受体介导与脊髓μ系统的协同作用。
