Antipruritic activity of the kappa-opioid receptor agonist, TRK-820.
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.
Togashi
Yuko
Y
Pharmaceutical Research Laboratories, Toray Industries, Inc., 1111 Tebiro Kamakura, Kanagawa 248-8555, Japan.
Umeuchi
Hideo
H
Okano
Kiyoshi
K
Ando
Naoki
N
Yoshizawa
Yoshitaka
Y
Honda
Toshiyuki
T
Kawamura
Kuniaki
K
Endoh
Takashi
T
Utsumi
Jun
J
Kamei
Junzo
J
Tanaka
Toshiaki
T
Nagase
Hiroshi
H
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
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