Opioid peptides: simultaneous delta agonism and mu antagonism in somatostatin analogues

Abstract

Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were made with beta-MePhe in position 1 and assayed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. The analogues displayed varying potencies and biological activities including: simultaneous delta receptor agonism/mu receptor antagonism, mu receptor antagonism, and delta receptor agonism. These analogues demonstrated that the N-terminal residue is important for receptor potency/selectivity and signal transduction. These analogues my represent leads to therapeutic agents that yield analgesia via delta agonist effects, yet lack side effects associated with mu activity.