Enkephalin analogs delta receptors

Mosberg, H.I., Hurst, R., Hruby, V.J., Gee, K., Akiyama. K., Yamamura, H.I., Galligan, J.J., Burks, T.F. Cyclic penicillamine containing enkephalin analogs display profound delta receptor selectivities, Life Sci 1983, 33 Suppl. 1, 447-50. 

This hypothesis of delta receptors in the mouse vas deferens was later further substantiated by the observation of the lack of cross-tolerance between a stable enkephalin analog [D-Ala2, D-leu5]enkephalin (DADLE, see below) and sulphentanyl (a mu agonist) in this tissue after chronic administration in vivo [8]. 

K. and Yamamura, H.I. (1983) Conformationally constrained cyclic enkephalin analogs with pronounced delta opioid receptor agonist selectivity. Life Sci. 32 2565-2569. 

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. 

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