Antinociceptive analogs of orphanin FQ/nociceptin(1-11) Journal Article
| Authors: | Mathis, J. P.; Goldberg, I. E.; Rossi, G. C.; Leventhal, L.; Pasternak, G. W. |
| Article Title: | Antinociceptive analogs of orphanin FQ/nociceptin(1-11) |
| Abstract: | The presence of pairs of basic amino acids within the sequence of orphanin FQ/nociceptin (OFQ/N) peptide, the endogenous ligand for the ORL1/KOR-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]OFQ/N(1-11) was highly epileptogenic, inducing naloxone-sensitive seizures in greater than 50% of the mice tested at doses comparable to those examined with the other analogs. These results indicate that it is possible to make analgesic OFQ/N(1-11) analogs. The activity of [IodoTyr10]OFQ/N(1-11) suggests that it may prove useful as a radioligand in exploring potential OFQ/N(1-11) binding sites. |
| Keywords: | unclassified drug; dose response; nonhuman; mouse; animals; mice; animal experiment; drug potency; drug synthesis; drug receptor binding; mice, inbred strains; molecular cloning; amino acid sequence; drug mechanism; peptide fragments; seizure; opioid; tail flick test; naloxone; nociceptors; opioid peptides; analgesic; antinociception; kappa opiate receptor; nociceptin; kappa3 receptor; subcutaneous drug administration; receptors, opioid; intracerebroventricular drug administration; male; article; orl1; nociceptin derivative; kor-3; nociceptin[1-11][1 tyrosine]; nociceptin[1-11][10 iodotyrosine]; nociceptin[1-11][10 tyrosine] |
| Journal Title: | Life Sciences |
| Volume: | 63 |
| Issue: | 11 |
| ISSN: | 0024-3205 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1998-08-07 |
| Start Page: | PL-161 |
| End Page: | PL-166 |
| Language: | English |
| PUBMED: | 9747901 |
| PROVIDER: | scopus |
| DOI: | 10.1016/S0024-3205(98)00358-0 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work