TY - JOUR
T1 - Nor-binaltorphimine, a highly selective kappa-opioid antagonist in analgesic and receptor binding assays
AU - Takemori, A. E.
AU - Ho, G. Y.
AU - Naeseth, J. S.
AU - Portoghese, P. S.
PY - 1988/1/1
Y1 - 1988/1/1
N2 - Previously, we reported on an opioid antagonist, nor-binaltorphimine (nor-BNI), that had high selectivity for kappa opioid receptors in smooth muscle preparations. In this study, nor-BNI administered either s.c. or i.c.v. was shown to antagonize significantly the antinociceptive effects of the kappa opioid agonists, ethylketazocine and U-50,488H at doses that had no effect on the antinociceptive effect of mu agonists, morphine and [D-Ala3, MePhe4, Gly-ol5]enkephalin and the delta agonist, [D-Pen3, D-Pen5]enkephalin. Nor-BNI and U-50,488H were used to demonstrate that kappa opioid receptors in the spinal cord were more important than those located supraspinally for kappa-mediated analgesia. Nor-BNI also possessed high affinity and high selectivity for kappa opioid receptors in the receptor binding assay. However, the comparatively low selectivity of BNI in receptor binding studies did not correlatet with the high pharmacologic selectivity for kappa receptors.
AB - Previously, we reported on an opioid antagonist, nor-binaltorphimine (nor-BNI), that had high selectivity for kappa opioid receptors in smooth muscle preparations. In this study, nor-BNI administered either s.c. or i.c.v. was shown to antagonize significantly the antinociceptive effects of the kappa opioid agonists, ethylketazocine and U-50,488H at doses that had no effect on the antinociceptive effect of mu agonists, morphine and [D-Ala3, MePhe4, Gly-ol5]enkephalin and the delta agonist, [D-Pen3, D-Pen5]enkephalin. Nor-BNI and U-50,488H were used to demonstrate that kappa opioid receptors in the spinal cord were more important than those located supraspinally for kappa-mediated analgesia. Nor-BNI also possessed high affinity and high selectivity for kappa opioid receptors in the receptor binding assay. However, the comparatively low selectivity of BNI in receptor binding studies did not correlatet with the high pharmacologic selectivity for kappa receptors.
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M3 - Article
C2 - 2839664
AN - SCOPUS:0023812719
SN - 0022-3565
VL - 246
SP - 255
EP - 258
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -