thiourea and Pruritus

The potential for itch production in human skin of the synthetic analogues of histamine, 2-methyl histamine (an H1-receptor agonist) and 4-methyl histamine and dimaprit (H2-receptor agonists) has been studied in vivo and compared with histamine. Itch thresholds for 2-methyl histamine were consistently much higher than for histamine (P < 0.001). The H1-receptor antagonist chlorpheniramine raised the itch thresholds to 2-methyl histamine and histamine significantly (P < 0.001). Pruritus was not obtained with either 4-methyl histamine or dimaprit. No evidence of synergism between 2-methyl histamine and either 4-methyl histamine or dimaprit was found. The results suggest that histamine-induced pruritus is mediated in part through the H1-receptor and in part via an additional (but probably non-H2) mechanism.

Topics: Adult; Chlorpheniramine; Dimaprit; Female; Histamine; Humans; Male; Methylhistamines; Pruritus; Receptors, Histamine H1; Receptors, Histamine H2; Skin; Thiourea

Effects of the histamine H(4) receptor antagonist JNJ 7777120 (1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine) were tested in two models of allergic contact dermatitis. Dermatitis was induced by 2,4-dinitrochlorobenzene and toluene-2,4-diisocyanate, which differ in their Th1-Th2 profile in that way that 2,4-dinitrochlorobenzene is a classical contact allergen with a pronounced Th1-mediated inflammation, while the respiratory chemical allergen toluene-2,4-diisocyanate induces a Th2-dominated inflammation. JNJ 7777120 (15 mg/kg) administered 2 h and 30 min before and 1 h after challenge did not reduce the hapten-induced ear swelling determined 24 h after challenge. This was confirmed by histological evaluation of the ear skin. A repeated administration of the haptens to the rostral part of the back of sensitized animals resulted in a frequent scratching behaviour. An administration of JNJ 7777120 (15 mg/kg) 30 min before challenge reduced this hapten-induced scratching significantly. The H(1) receptor antagonist cetirizine also reduced the scratching bouts in sensitized mice. A combination of H(1) and H(4) receptor antagonists resulted in the strongest inhibition of scratching behaviour associated with allergic dermatitis. These results indicate that H(4) receptor antagonism fails to reduce the allergic inflammatory response but strongly inhibits allergen-induced itch. Thus, a combination of H(4) and H(1) receptor antagonism might be a new strategy to treat pruritus related to allergic diseases like atopic dermatitis.

Topics: Animals; Dermatitis, Atopic; Dose-Response Relationship, Drug; Female; Haptens; Histamine H1 Antagonists; Imidazoles; Indoles; Inflammation; Mice; Mice, Inbred BALB C; Piperazines; Pruritus; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4; Th2 Cells; Thiourea; Time Factors

The present study was performed to study the participation of histamine H(3) receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H(3) receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H(3)-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H(1)-receptor antagonist, cetirizine. Furthermore, simultaneous use of H(3)-receptor agonists, Sch 50971 or imetit, and an H(1)-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy.

Topics: Animals; Anti-Allergic Agents; Cetirizine; Chemotaxis, Leukocyte; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Eosinophils; Female; Histamine Agonists; Histamine H1 Antagonists, Non-Sedating; Imidazoles; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Pruritus; Pyrrolidines; Receptors, Histamine H3; Rhinitis, Allergic, Perennial; Sneezing; Thiourea; Time Factors