Pharmacological Characterization of Nociceptin/Orphanin FQ Receptors, a Novel Opioid Receptor Family, in the Midbrain Periaqueductal Gray
Chiou LC, Fan SH, Chuang KC, Liao YY, Lee SZ.
Department of Pharmacology,
College of Medicine,
National Taiwan University,
No. 1, Jen-Ai Rd., Section 1,
Taipei 100, Taiwan.
Ann N Y Acad Sci. 2004 Nov;1025:398-403


A fourth opioid receptor family was cloned and named after its endogenous ligand as nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor. We have characterized several NOP receptor ligands pharmacologically at native NOP receptors of ventrolateral periaqueductal gray (vlPAG) neurons by investigating their interactions with N/OFQ in activating G protein-coupled inwardly rectifying K(+) (GIRK) channels. They are listed here: (1) [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)NH(2), which was claimed to be the first selective antagonist of NOP receptors, is a partial agonist of NOP receptors in vlPAG neurons. (2) [Nphe(1)]N/OFQ(1-13)NH(2) is a pure, selective, and competitive peptide antagonist of NOP receptors (pA2 value = 6.6). (3) CompB (J-113397) is a potent and selective nonpeptide antagonist of NOP receptors (pA2 = 8.4). (4) Naloxone benzoylhydrazone is a competitive NOP receptor antagonist but also a noncompetitive mu-opioid receptor antagonist. (5) Ro 64-6198, though being developed as a potent nonpeptide NOP receptor agonist, affected only part of vlPAG neurons and acted as a weak NOP receptor agonist. In Ro 64-6198-unresponsive neurons, N/OFQ activated GIRK channels through NOP receptors. (6) Nocistatin, a functional antagonist of N/OFQ in the spinal cord, did not affect the effect of N/OFQ in most of the recorded neurons. Our functional studies of NOP receptor ligands at native brain NOP receptors reveal that some of them act differently from those at expressed receptors of cell cultures.
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Orphanin/nociceptin: history
Nociceptin/orphanin and dopamine
Nociceptin antagonists: aminoquinolones
Nociceptin antagonists as antidepressants

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