The cannabinoid CB2 receptor inverse agonist JTE-907 suppresses spontaneous itch-associated responses of NC mice, a model of atopic dermatitis.
JTE-907, N-(benzo[1,3]dioxol-5-ylmethyl)-7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxamide, is a selective cannabinoid CB2 receptor antagonist/inverse agonist. The anti-pruritic activity of JTE-907 was studied in NC mice with chronic dermatitis, a model of atopic dermatitis. The oral dose of JTE-907 (1 and 10 mg/kg/day), an immunosuppressant agent tacrolimus (1 mg/kg/day) and a glucocorticoid betamethasone 17-valerate (1 mg/kg/day) for 20 days suppressed the spontaneous scratching and cutaneous nerve activity of NC mice. JTE-907 (10, but not 1, mg/kg) and tacrolimus, but not betamethasone, tended to alleviate the dermatitis. Betamethasone inhibited the body weight gain. These results suggest that JTE-907 suppresses spontaneous itch-associated responses of NC mice without adverse effects such as weight loss.
Maekawa
Tatsuya
T
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Nojima
Hiroshi
H
Kuraishi
Yasushi
Y
Aisaka
Kazuo
K
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011537:Pruritus / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D012720:Severity of Illness Index; D012867:Skin / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology
D004149:Dioxoles; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C422645:JTE 907; D015363:Quinolones; D043885:Receptor, Cannabinoid, CB2; D001624:Betamethasone Valerate; D016559:Tacrolimus