Opioid receptor binding and in vivo antinociceptive activity of position 3-substituted morphiceptin analogs

Analogs of morphiceptin (Tyr-Pro-Phe-Pro-NH 2), a μ-selective opioid receptor ligand, with position 3-modifications, including altered size, lipophilicity, and electronic character, while maintaining aromaticity were synthesized. The activity of the new analogs in in vitro assays and in in vivo hot-...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-07, Vol.320 (2), p.531-536
Main Authors: Fichna, Jakub, do-Rego, Jean-Claude, Costentin, Jean, Chung, Nga N, Schiller, Peter W, Kosson, Piotr, Janecka, Anna
Format: Article
Language:English
Subjects:
Analgesics, Opioid - metabolism
Analgesics, Opioid - pharmacology
Animals
Antinociception
Endorphins - chemistry
Endorphins - metabolism
Endorphins - pharmacology
Hot plate
Mice
Morphiceptin
Opioid peptide
Protein Binding
Rats
Rats, Wistar
Receptors, Opioid - metabolism
Structure-Activity Relationship
μ-Opioid receptor
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Summary:Analogs of morphiceptin (Tyr-Pro-Phe-Pro-NH 2), a μ-selective opioid receptor ligand, with position 3-modifications, including altered size, lipophilicity, and electronic character, while maintaining aromaticity were synthesized. The activity of the new analogs in in vitro assays and in in vivo hot-plate test of analgesia was compared and the results were consistent. [ d-1-Nal 3]Morphiceptin was the most potent analog of this series with a 26-fold increase in μ-opioid receptor affinity, a 15-fold potency increase in the GPI assay, and a significant potency increase in the hot-plate analgesic test, as compared with morphiceptin. [ d-Qal 3]Morphiceptin was found to be a weak antagonist in the GPI assay.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2004.05.202