OPIOID-PEPTIDES - SIMULTANEOUS DELTA-AGONISM AND MU-ANTAGONISM IN SOMATOSTATIN ANALOGS

Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Th r-Pen-Thr-NH2 (CTAP) were made with beta-MePhe in position 1 and assay ed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. These 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 pot ency/selectivity and signal transduction. These analogues may represen t leads to therapeutic agents that yield analgesia via delta agonist e ffects, yet lack side effects associated with mu activity. (C) 1997 El sevier Science Inc.