Selective delta receptor ligand

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. 

TABLE 1 Binding Affinities for Selective Opioid Receptor Ligands to Membrane Preparations from COS-7 Cells, Transiently Transfected with the Cloned Human Delta Opioid Receptor... 

Delorme D, Berthelette C, Lavoie R, Roberts E (1998) Asymmetric synthesis of diarylmethy-lamines preparation of selective opioid delta receptor ligands. Tetrahedron Asymmetry 9 3963-3966... 

Today, we know that there are three types of opioid receptors—mu, delta, and kappa receptors [see review 3]. Proenkephalin contains six copies of Met-enkephalins and one copy of Leu-enkephalin. Enkephalins, especially Leu-enkephalin, are believed to be selective to delta receptors. Opiomelano-cortin contains (3-endorphin that has the Met-enkephalin at its amino terminus. (3-Endorphin is a nonselective ligand for mu and delta receptors. 

Although above mentioned delta and mu receptor selective peptides and opiates were observed and useful for the identification of distinctive delta receptor from other opioid receptors, they suffered from the low selectivity and cross-actions at high doses or concentrations of these ligands, especially in in vivo pharmacological studies. The needs of having highly selective ligands for all types of opioid receptors were clear. In addition to the above... 

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. 

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