title: Antipruritic activity of the kappa-opioid receptor agonist, TRK-820.
abstract: The effects of the kappa-opioid receptor agonist, TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, on the itch sensation were compared with those of histamine H1 receptor antagonists, using the mouse pruritogen-induced scratching model. Peroral administration of TRK-820 reduced the numbers of substance P- or histamine-induced scratches dose dependently. No obvious suppression of the spontaneous locomotor activity was observed at the doses used for the experiments, indicating that the inhibition of scratches was not due to the effect on general behavior. Furthermore, the scratching inhibitory activity of TRK-820 was dose dependently antagonized by the specific kappa-opioid receptor antagonist, nor-binaltorphimine, suggesting that the inhibitory activity was mediated via kappa-opioid receptors. Histamine H1 receptor antagonists, chlorpheniramine and ketotifen, did not inhibit substance P-induced scratches, or did so only partially. Both antihistamines inhibited the histamine-induced scratches completely. These results suggest that TRK-820 has antipruritic activity which is mediated by kappa-opioid receptors, and is effective in both antihistamine-sensitive and -resistant pruritus.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 1111 Tebiro Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Togashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Umeuchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okano
authors.forename: Naoki
authors.initials: N
authors.lastname: Ando
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoshizawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Honda
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Kawamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Endoh
authors.forename: Jun
authors.initials: J
authors.lastname: Utsumi
authors.forename: Junzo
authors.initials: J
authors.lastname: Kamei
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000627:therapeutic use*; D002744:Chlorpheniramine / Q000627:therapeutic use; D004195:Disease Models, Animal; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D007665:Ketotifen / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009019:Morphinans / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy*; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D013141:Spiro Compounds / Q000627:therapeutic use*; D013373:Substance P / Q000494:pharmacology
chemical_list: D000982:Antipruritics; D006634:Histamine H1 Antagonists; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820; D013373:Substance P; C051844:norbinaltorphimine; D002744:Chlorpheniramine; D009271:Naltrexone; D006632:Histamine; D007665:Ketotifen