Opioid antagonists and methods of their use

Details Opioid antagonists and methods of their use Opioid antagonists and methods of their use

1995-11-03

1998-10-13

Walsh, Stephen

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

530350, A61K 3803, G07K 14575

Patent

active

058212191

ABSTRACT:
The present invention relates to a novel mammalian anti-opioid receptor protein (OFQR), peptide ligands (such as OFQ) that bind to OFQR, and methods of using the OFQ peptide and analogues to reverse the physiologic effects of opiates such as morphine. The isolation, characterization and pharmacological use of the endogenous peptide ligand is described. A particular embodiment of the OFQ peptide is a heptadecapeptide having an FGGF aminoterminal motif. The peptide specifically binds to an OFQ receptor protein heterologously expressed in mammalian cells. The peptide does not bind with high affinity to .mu., .delta. or .kappa. receptors, but it antagonizes opioid mediated effects (such as analgesia and hypothermia) without increasing nociceptive sensitivity. Tyrosine substitution variants of the peptide ligand specifically bind to the opioid receptor and can be radioiodinated. Also provided are methods of making such peptide ligands and OFQR antagonists, and methods of using the ligands for diagnostic and therapeutic uses and for the identification of other naturally-occurring or synthetic opioid receptor ligands.

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