DPDPE mechanism

In conclusion, the in vivo activity of available delta opioids is complex. DPDPE, or even Delt, administered ICV seems to recruit mu receptors and, from all the data, it appears that delta agonists often have mixed mu/ delta activities. More selective delta agonists need to be produced to explore delta receptor pharmacology. The examination of nonanalgesic activities of delta ligands in opioid receptor knockout mice has been very informative while the convulsive effect of SNC 80 seems indeed delta receptor mediated, the addictive activity of Delt most probably results from mu receptor activation and the immunosuppressive action of NTI is mediated by a nonopioid mechanism. 

Conformational analyses of JOM-13 and [L-Ala3]DPDPE have proven to be critical for the determination of the bioactive conformation of enkephalin-like peptides at the delta receptor. H-NMR studies of JOM-13 in aqueous solution revealed that this tetrapeptide exists in two distinct conformations on the NMR time scale as evidenced by two sets of resonances [63]. Large differences in the observed chemical shifts and coupling constants for the D-Cys2 residue in the two conformers suggested that the major differences between the two NMR conformers reside in the disulfide portion of the molecule however, a paucity of conformationally informative nuclear Overhauser enhancement (NOE) interactions precluded the development of a detailed structural model from the NMR studies. In order to develop such a model a thorough conformational analysis of JOM-13 was undertaken, in which the NMR data were complemented by x-ray diffraction results and by molecular mechanics calculations [64]. The results indicate that the 11-... 

There is considerable evidence that 5r and 2-opioid receptors act at supraspinal sites to modulate nociceptive responses. Direct ICV injection of the putative 5-opioid agonists DPDPE or DPLPE in the mouse produced dose-dependent antinociception that was blocked by ICI 174,864 but not by (5-FNA [87,88]. Furthermore, 5-opioid selective doses of DPDPE given ICV blocked nociception, but not gastrointestinal transit, in mice [99].The ICV administration of DPDPE has been shown to produce dose-dependent antinociception against mechanical nociception (Randall-Selitto paw with-... 

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