Analogues of beta-LPH61-64 possessing selective agonist activity at mu-opiate receptors.
Peptides based in the stabilised tetrapeptide HTyr-D-Ala-Gly-MePheOH have been synthesised and shown to have substantial opioid activity both in vitro and in vivo. The selectivity of these compounds of different receptor populations has been investigated using both isolated tissue assays and binding studies. Results suggest that the compounds are potent agonists at mu-receptors with little or no affinity for the delta-receptor population. One of the compounds, RX783006 (HTyr-D-Ala-Gly-MePhe-NH(CH2)2OH), has been tritiated to high specific radioactivity and may prove to be a useful probe in the elucidation of the function of the heterogenous opiate receptor population.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects; D008083:beta-Lipotropin / Q000378:metabolism*
D004745:Enkephalins; D010446:Peptide Fragments; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D008083:beta-Lipotropin