title: Characterization of the antinociceptive effects of TRK-820 in the rat.
abstract: 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.
authors.affiliation: Basic Research Laboratories, Toray Industries, 1111, Tebiro, Kamakura, Japan. takashi_endo@nts.toray.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Endoh
authors.forename: A
authors.initials: A
authors.lastname: Tajima
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Kamei
authors.forename: M
authors.initials: M
authors.lastname: Narita
authors.forename: L
authors.initials: L
authors.lastname: Tseng
authors.forename: H
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D009019:Morphinans; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C058468:ICI 199441; C111212:TRK 820