Hexahydro derivative of (D-Met2, Pro-NH2(5)]-enkephalin gives rise to physical dependence.
Filippi et al. (1979) have claimed that substitution of cyclohexylalanine for phenylalanine in leucine-enkephalin and its L-Ser3 derivative resulted in synthetic analogs which were non-addicting. We have examined the hexahydro derivative of [D-Met2, Pro-NH2(5)]-enkephalin, a potent analgesic agent, to determine if dependence liability can be separated from short-term opiate actions after hydrogenation of the phenylalanine residue. In contrast to Filippi et al.'s observations, we found that the hexahydro derivative of [D-Met2, Pro-NH2(5)]-enkephalin gives rise to physical dependence and that its short-term potencies generally paralleled its long-term ability to produce physical dependence.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001681:Biological Assay; D004723:Endorphins / Q000138:chemical synthesis*; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D007202:Indicators and Reagents; D008722:Methods; D051379:Mice; D051381:Rats; D019966:Substance-Related Disorders
D004723:Endorphins; D004745:Enkephalins; D007202:Indicators and Reagents