Characterization of the antinociceptive effects of TRK-820 in the rat

Eur J Pharmacol. 2000 Jan 10;387(2):133-40. doi: 10.1016/s0014-2999(99)00815-8.


We have already reported that TRK-820, (-)-17-cyclopropylmethyl-3, 14b-dihydroxy-4, 5a-epoxy-6b-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan hydrochloride, a new selective kappa-opioid receptor agonist, has affinity for kappa-subtype opioid receptors other than the kappa(1)-opioid receptor. It would be of interest to examine whether the different kappa-opioid receptor subtype properties of TRK-820 participate in its antinociceptive action in the inflamed paw test and the formalin test. TRK-820 produced a potent antinociceptive effect, which was inhibited by the selective kappa-opioid receptor antagonist nor-binaltorphimine, but not by the mu-opioid receptor antagonist naloxone in the mechanical paw pressure test. TRK-820 also produced a potent antinociceptive effect in rats with adjuvant-induced arthritis. TRK-820 and morphine, a prototype mu-opioid receptor agonist, were equally effective in inhibiting the nociceptive responses in the arthritic rats and in the normal rats, while ICI-199441, 2-(3, 4-dichlorophenyl)-N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]- acetamide, a kappa-opioid receptor agonist, was about 5-fold less potent in the arthritic rats than in the normal rats. In the formalin test TRK-820 had a very similar antinociceptive potency to that of ICI-199441, unlike in the arthritic rats in which TRK-820 was 2.5 times more potent than ICI-199441. It is concluded that TRK-820 produced a potent antinociceptive action via the stimulation of kappa-opioid receptors in rats. TRK-820 has a unique antinociceptive profile different from that of the other kappa-opioid receptor agonists such as ICI-199441 in arthritic rats.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Hyperalgesia / drug therapy
  • Male
  • Morphinans / pharmacology*
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, kappa / agonists*
  • Spiro Compounds / pharmacology*


  • Analgesics, Opioid
  • Morphinans
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • Spiro Compounds
  • ICI 199441
  • TRK 820