title: Histamine H(4) receptor antagonist reduces dermal inflammation and pruritus in a hapten-induced experimental model.
abstract: Effects of the histamine H(4) receptor antagonist 1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine (JNJ7777120) were examined for 99 days in a long-term experimental model of pruritic dermatitis induced by repeated challenge with 2,4,6-trinitrochlorobenzene (TNCB) in HR-1 mice. Repeated application of TNCB to the back skin of mice elicited frequent scratching behavior and skin lesions at 24 h after challenge and beyond. JNJ7777120 (10 and 30 mg/kg) reduced this scratching behavior and ameliorated the skin lesions in a dose-dependent manner, whereas the histamine H(1) receptor antagonist fexofenadine had no such effect and did not reduce the inflammation score, even though dexamethasone reduced the scratching bouts. Each of the three agents reduced the increase in the serum IgE concentration induced by TNCB, but only JNJ7777120 reduced the number of mast cells in the skin lesions elicited by repeated application of TNCB. These results indicate that treatment with a H(4) receptor antagonist may be effective for amelioration of both skin inflammation and pruritus in patients with allergic dermatitis such as atopic dermatitis.
authors.affiliation: Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Suwa
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yamaura
authors.forename: Manabu
authors.initials: M
authors.lastname: Oda
authors.forename: Takao
authors.initials: T
authors.lastname: Namiki
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueno
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006633:Histamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000097:blood; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D015847:Interleukin-4 / Q000235:genetics; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless; D010853:Picryl Chloride / Q000009:adverse effects*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011537:Pruritus / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D012867:Skin / Q000187:drug effects
chemical_list: D006633:Histamine Antagonists; C498829:Hrh4 protein, mouse; D007074:Immunoglobulin G; D007211:Indoles; D010879:Piperazines; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D015847:Interleukin-4; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D010853:Picryl Chloride