Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA treatment.

ABSTRACT: Previously, we reported that H-2',6'-dimethyltyrosine [Dmt(1)]-d-Arg-Phe-Lys-NH(2) (DALDA), an analogue of the naturally occurring opioid peptide dermorphin, is a highly potent and selective mu receptor agonist with low cross-tolerance to morphine. In the present study, we investigated the effect of treating mice chronically with [Dmt(1)]DALDA. The AD(50) of [Dmt(1)]DALDA (s.c.) increased eight-fold in animals given this drug chronically; in contrast, the AD(50) increased two-fold in mice chronically treated with morphine. The AD(50) of morphine (s.c.) in these [Dmt(1)]DALDA-treated animals was increased more than 120 times, while that of the more selective mu agonist [d-Ala(2)-MePhe(4)-Gly-ol(5)]enkephalin (DAMGO) given intrathecally was increased more than 240 times. However, the AD(50)

SUBMITTER: Ben Y 

PROVIDER: S-EPMC1575960 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature