title: S-777469, a novel cannabinoid type 2 receptor agonist, suppresses itch-associated scratching behavior in rodents through inhibition of itch signal transmission.
abstract: We have previously reported that S-777469 [1-([6-ethyl-1-(4-fluorobenzyl)-5-methyl-2-oxo-1,2-dihydropyridine-3-carbonyl]amino)-cyclohexanecarboxylic acid], a novel cannabinoid type 2 receptor (CB2) agonist, significantly suppressed compound 48/80-induced scratching behavior in mice in a dose-dependent manner when it was administered orally. Here, we demonstrated that the inhibitory effects of S-777469 on compound 48/80-induced scratching behavior are reversed by pretreatment with SR144528, a CB2-selective antagonist. In addition, we investigated the effects of S-777469 on itch-associated scratching behavior induced by several pruritogenic agents in mice and rats. S-777469 significantly suppressed scratching behavior induced by histamine or substance P in mice or by serotonin in rats. In contrast, the H1-antihistamine fexofenadine clearly inhibited histamine-induced scratching behavior but did not affect scratching behavior induced by substance P or serotonin. Moreover, S-777469 significantly inhibited histamine-induced peripheral nerve firing in mice. In conclusion, these results suggest that S-777469 produces its antipruritic effects by inhibiting itch signal transmission through CB2 agonism.
authors.forename: Takayo
authors.initials: T
authors.lastname: Haruna
authors.forename: Masahiko
authors.initials: M
authors.lastname: Soga
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Morioka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hikita
authors.forename: Kinichi
authors.initials: K
authors.lastname: Imura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furue
authors.forename: Mina
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Chihiro
authors.initials: C
authors.lastname: Imura
authors.forename: Minoru
authors.initials: M
authors.lastname: Ikeda
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Deguchi
authors.forename: Michitaka
authors.initials: M
authors.lastname: Shichijo
authors.forename: Akinori
authors.initials: A
authors.lastname: Arimura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yasui
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006632:Histamine; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011728:Pyridones / Q000494:pharmacology* / Q000627:therapeutic use*; D011916:Rats, Inbred F344; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D012701:Serotonin; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine
chemical_list: D011728:Pyridones; D043885:Receptor, Cannabinoid, CB2; C574957:S-777469; D012701:Serotonin; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine