Pharmacological profiles of a novel opioid receptor-like1 (ORL(1)) receptor antagonist, JTC-801

Br J Pharmacol. 2002 Jan;135(2):323-32. doi: 10.1038/sj.bjp.0704478.


Pharmacological effects of a novel opioid receptor-like1 (ORL(1)) receptor antagonist, [N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride] (JTC-801), were examined in in vitro and in vivo. JTC-801 inhibited the binding of [(3)H]-nociceptin to human ORL(1) receptors expressed in HeLa cells with a K(i) value of 44.5 nM. JTC-801 completely antagonized the suppression of nociceptin on forskolin-induced accumulation of cyclic AMP (IC(50) : 2.58 microM) using ORL(1) receptor expressing HeLa cells in vitro. In in vivo, when given intravenously at dosages of 0.01 mg kg(-1) and above, or orally at dosages 1 mg kg(-1) and above, JTC-801 antagonized the nociceptin-induced allodynia in mice. Effects of JTC-801 on various nociceptive models were examined. In mouse hot-plate test, JTC-801 prolonged escape response latency (ERL) to exposed heat stimulus with minimum effective doses (MED) of 0.01 mg kg(-1) by i.v. or 1 mg kg(-1) by p.o. In the rat formalin test, JTC-801 reduced both the first and second phases of the nociceptive response with MED of 0.01 mg kg(-1) by i.v. administration or 1 mg kg(-1) by p.o. administration. This anti-nociceptive action of JTC-801 was not inhibited by naloxone (10 mg kg(-1), s.c.). We have demonstrated that JTC-801 antagonizes the ORL(1) receptor response, and that JTC-801 has efficacious and potent anti-nociceptive effects in acute pain animal models not only by intravenous injection but also oral administration. These results suggest that JTC-801 may represent a new class of analgesics.

MeSH terms

  • Aminoquinolines / metabolism*
  • Aminoquinolines / pharmacology*
  • Animals
  • Benzamides / metabolism*
  • Benzamides / pharmacology*
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred ICR
  • Narcotic Antagonists* / metabolism*
  • Narcotic Antagonists* / pharmacology*
  • Opioid Peptides / metabolism
  • Pain Measurement / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / metabolism*


  • Aminoquinolines
  • Benzamides
  • N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide
  • Narcotic Antagonists
  • Opioid Peptides
  • Receptors, Opioid
  • nociceptin
  • nociceptin receptor
  • Cyclic AMP