DPDPE, selective ligand

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. 

As reported in Table 2, the observed ligand selectivity pattern for the lysed-P2-deltancx (delta) and lysed-P2-deltacx (mu) sites were as expected. Compounds such as DPDPE were potent at the lysed-P2-deltancx site and... 

It is of particular interest that another 8 opioid selective nonpeptidic piperazine derivative agonist, SL-3111 (l-(4-/ert-butyl-3 -hydroxy)benzhydryl-4-benzylpiper-azine), was designed and synthesized based on the identification of the essential pharmacophores for peptide ligands to interact with 8 receptors, and on a model of the proposed bioactive conformation of the potent, conformationally constrained 8-opioid peptide ligand [(25,3/ )-TMT1]DPDPE [47]. This new series used the... 

Early efforts to convert enkephalin into a selective 6-opioid ligand were successful in the development of c[D-Pen, D-Pen ]enkephalin (21 l)(DPDPE)and its analogs, which eventually led to analogs that were essentially specific for 8-opioid receptors as agonists, such as (2S,3i )j3-methyl-2, 6 -dimethyl tyrosine-c[D-Pen, u-Pen ]enkephalin (212, 213). The earlier aspects of this work have been thoroughly reviewed (214) and a selective update has recently appeared (215). A different kind of lead to 6-opioid ligands came from the discovery of the deltorphins (216, 217) such as H-Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 that are found in amphibian skins and have intrinsically highly delta opioid receptor selectivity. 

Adequate modifications and alterations in the amino-acid sequence and composition of the enkephalins (pentapeptides produced in the brain) give rise to sueh eompoimds that signifieantly demonstrate both high poteney and distinet selectivity for the delta opioid receptors. James et. al. (1984) introdueed [D-Ala, D-Leu ] enkephalin, also termed as DADLE whereas, Mosberg et al. (1983) introdueed the eyelie peptide [D-Pen, D-Pen ] enkephalin, also known as DPDPE, whieh enjoyed the reputation of being the peptides invariably and frequently employed as selective delta receptor ligands. 

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