[Effect of TRK-820, a selective kappa opioid receptor agonist, on scratching behavior in an animal model of atopic dermatitis].
In atopic dermatitis patients, pruritus is a severe symptom that is difficult to treat. It is previously reported that TRK-820, a kappa-opioid receptor agonist, reduces murine scratching behavior induced by an intradermal injection of histamine or substance P or an intracisternal injection of morphine. It is also reported that TRK-820 ameliorates the intractable pruritus in hemodialysis patients. However, it is still unclear whether TRK-820 possesses antipruritic effects on the pruritus in dermatitis patients. Therefore, the effect of TRK-820 on scratching behavior in NC/Nga mice maintained in a conventional environment, an animal model of atopic dermatitis, was examined. Oral TRK-820 (10-100 microg/kg) inhibited the scratching behavior but did not affect the locomotor activity. On the other hand, ketotifen (3-30 mg/kg, po), an antihistamine, did not attenuate the scratching behavior. TRK-820 showed the highest selectivity and activity for kappa-opioid receptor among all human opioid receptors. Release of various inflammatory mediators from a variety of cells and activity of nitric oxide synthase were not altered by TRK-820. This compound showed much lower affinities for other receptors than that for opioid receptors. These results suggest that TRK-820 is effective against antihistamine-resistant pruritus in atopic dermatitis patients via the kappa opioid receptor.
Nakao
Kaoru
K
Pharmaceutical Research Laboratories, Toray Industry, Inc., 10-1 Tebiro 6-chome, Kamakura, 248-8555 Japan. Kaoru_Nakao@nts.toray.co.jp
Ikeda
Ken
K
Kurokawa
Takahiro
T
Togashi
Yuko
Y
Umeuchi
Hideo
H
Honda
Toshiyuki
T
Okano
Kiyoshi
K
Mochizuki
Hidenori
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003876:Dermatitis, Atopic / Q000150:complications* / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009019:Morphinans / Q000494:pharmacology* / Q000627:therapeutic use*; D011537:Pruritus / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013141:Spiro Compounds / Q000494:pharmacology* / Q000627:therapeutic use*
D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820