Involvement of substance P in scratching behaviour in an atopic dermatitis model.
Substance P is speculated to be a key mediator of itching in atopic dermatitis, possibly acting via the tachykinin NK1 receptor. Thus, we examined the effect of a tachykinin NK1 antagonist, BIIF 1149 CL, on scratching behaviour in a picrylchloride-induced dermatitis model in NC/Nga mice. BIIF 1149 CL ((S)-N-[2-[3,5-bis(trifluoromethyl) phenyl]ethyl]-4-(cyclopropylmethyl)-N-methyl-alpha-phenyl-1-piperazineacetamide, monohydrochloride, monohydrate) at a dose of 100 mg/kg, p.o., significantly inhibited scratching behaviour immediately after administration, and the effect continued up to 6 h. The results suggest that clinical trials of tachykinin NK1 antagonists for the treatment of itching in atopic dermatitis patients would be warranted.
Ohmura
Tsuyoshi
T
Department of Pharmacology, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim, Co., Ltd., 3-10-1 Yato, Kawanishi, 666-0193, Japan. ohmura@boehringer-ingelheim.co.jp
Hayashi
Toshihiro
T
Satoh
Yayoi
Y
Konomi
Ayako
A
Jung
Birgit
B
Satoh
Hisashi
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy*; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000633:toxicity; D015320:Tachykinins / Q000494:pharmacology / Q000627:therapeutic use
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; D013373:Substance P