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The presence of pairs of basic amino acids within the sequence of orphanin FQ/nociceptin (OFQ/N) peptide, the endogenous ligand for the ORL₁KOR-3 receptor, has raised the possibility that processing might generate pharmacologically important truncated peptides, including OFQ/N(1–11). OFQ/N(1–11) is pharmacologically active in vivo with a potency comparable to OFQ/N. Several tyrosine-containing analogs of OFQ/N(1–11) have been synthesized and examined for antinociceptive activity. Like OFQ/N(1–11), [Tyr¹]OFQ/N(1–11), [Tyr¹⁰]OFQ/N(1–11) and [IodoTyr¹⁰]OFQ/N(1–11) given supraspinally in mice were antinociceptive in the tailflick assay in mice. The tyrosine analogs showed similar potencies as OFQ/N(1–11) but longer durations of action. This response was readily reversed by the opioid antagonist naloxone despite poor affinities for these analogs at opioid receptors. Another compound, [Tyr¹¹ …