CompB (J-113397), selectively and competitively antagonizes nociceptin activation of inwardly rectifying K+ channels in rat periaqueductal gray slices

Chiou, Lih‐Chu; Fan, Shu-Huai

doi:10.1016/s0028-3908(02)00051-5

Cited by 20 publications

(6 citation statements)

References 36 publications

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“…The Banyu Company renamed this chiral compound as CompB, which was shown to be more potent than the racemic mixture 21. In vlPAG neurons, we have demonstrated that CompB is a pure, selective, and competitive NOP receptor antagonist with a pA 2 value of 8.37 22…”

Section: Compb (J‐113397)mentioning

confidence: 79%

Pharmacological Characterization of Nociceptin/Orphanin FQ Receptors, a Novel Opioid Receptor Family, in the Midbrain Periaqueductal Gray

Chiou

Fan

Chuang

et al. 2004

Annals of the New York Academy of Sciences

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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) [Phe1Psi(CH2-NH)Gly2]N/OFQ(1-13)NH2, which was claimed to be the first selective antagonist of NOP receptors, is a partial agonist of NOP receptors in vlPAG neurons. (2) [Nphe1]N/OFQ(1-13)NH2 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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Section: Compb (J‐113397)mentioning

confidence: 79%

Pharmacological Characterization of Nociceptin/Orphanin FQ Receptors, a Novel Opioid Receptor Family, in the Midbrain Periaqueductal Gray

Chiou

Fan

Chuang

et al. 2004

Annals of the New York Academy of Sciences

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“…In the current study, we blocked endogenous N/OFQ signals with ( 8 )-J 113397, a nonpeptidic NOP antagonist. The role of this drug has been confirmed in both in vitro [28] and in vivo [29] assays.…”

mentioning

confidence: 86%

The Functional Antiopioid Action of the Ventrolateral Periaqueductal Gray Nociceptin/Orphanin FQ and Nociceptin Receptor System Underlies DAMGO Analgesic Tolerance

Parenti

Scoto²

2010

Pharmacology

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Nociceptin/Orphanin FQ (N/OFQ) counteracts supraspinal opioid effects and plays a role in antinociceptive morphine tolerance. Therefore, in the present study, the selective µ-opioid agonist [D-Ala²-NMe-Phe⁴-Gly-ol⁵]-enkephalin (DAMGO) was used. Repeated injection of DAMGO (1 µg/ 1 µl) into the ventrolateral periaqueductal gray (vlPAG), a key site for the development of opioid tolerance, induced analgesia that lasted up to 3 days. In DAMGO-tolerant rats, injection of the N/OFQ antagonist (±)-J 113397 (4 µg/1 µl), into the same site, restored the antinociceptive effect of DAMGO. If (±)-J 113397 treatment preceded each DAMGO injection, tolerance did not develop. Inhibition of N/OFQ signaling can reverse and prevent the development of DAMGO tolerance in the vlPAG. The results confirm that N/OFQ acts as a functional opioid antagonist.

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“…Quantitative studies indicated that it is a competitive antagonist of cloned NOP receptors and native NOP receptors in brain tissues with pA2 values of 8.2 ~ 8.9 [68][69][70] (Table 2). Banyu Company renamed this chiral isomer as CompB, which is more potent than the racemic mixture [71].…”

Section: Non-peptide Antagonistsmentioning

confidence: 99%

Relaxin Receptors - New Drug Targets for Multiple Disease States

Westhuizen

Summers²,

Halls

et al. 2007

CDT

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Relaxin was discovered more than 75 years prior to the identification of the receptors that mediate its actions. There has been a slow emergence in understanding the role of relaxin, with it being denoted initially as a hormone of pregnancy due to its observed effects to relax pubic ligaments and soften the cervix of guinea pigs to facilitate parturition. However, many other physiological roles have been identified for relaxin, including cardiovascular and neuropeptide functions and an ability to induce the matrix metalloproteinases, so it is clear that relaxin is not exclusively a hormone of pregnancy but has a much wider role in vivo. The recent de-orphanisation of four receptors LGR7, LGR8, GPCR135 (SALPR) and GPCR142 (GPR100) that respond to and bind at least one of the three forms of relaxin identified to date, allows dissection of this system to determine the precise role of each receptor and enable the identification of new targets for treatment of numerous disease states. Relaxin has the potential to be useful for the treatment of scleroderma, fibrosis, in orthodontics and to facilitate embryo implantation in humans. Relaxin antagonists may act as contraceptives or prevent the development of breast cancer metastases. Recent research has added considerable knowledge to the signalling pathways activated by relaxin, which will aid our understanding of how relaxin produces its effects. The focus of this review is to bring together recent developments in the relaxin receptor field and to highlight their potential as drug targets.

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CompB (J-113397), selectively and competitively antagonizes nociceptin activation of inwardly rectifying K+ channels in rat periaqueductal gray slices

Cited by 20 publications

References 36 publications

Pharmacological Characterization of Nociceptin/Orphanin FQ Receptors, a Novel Opioid Receptor Family, in the Midbrain Periaqueductal Gray

Pharmacological Characterization of Nociceptin/Orphanin FQ Receptors, a Novel Opioid Receptor Family, in the Midbrain Periaqueductal Gray

The Functional Antiopioid Action of the Ventrolateral Periaqueductal Gray Nociceptin/Orphanin FQ and Nociceptin Receptor System Underlies DAMGO Analgesic Tolerance

Relaxin Receptors - New Drug Targets for Multiple Disease States

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