Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus

Histamine is a potent mediator of itch in humans, yet histamine H(1) receptor antagonists have been shown to be of limited use in the treatment of certain chronic pruritic diseases. The histamine H(4) receptor is a recently described histamine receptor, expressed on hematopoietic cells, linked to the pathology of allergy and asthma.The contribution of the novel histamine H(4) receptor to histaminergic and allergic pruritus was investigated.Histamine and a selective histamine H(4) receptor agonist caused scratching responses in mice, which were almost completely attenuated in histamine H(4) receptor knockout mice or by pretreatment with the selective histamine H(4) receptor antagonist, JNJ 7777120. Pruritus induced by allergic mechanisms was also potently inhibited with histamine H(4) receptor antagonist treatment or in histamine H(4) receptor knockout mice. In all cases, the inhibitory effect of histamine H(4) receptor antagonist was greater than those observed with histamine H(1) receptor antagonists. The histamine H(4) receptor-mediated pruritus was shown to be independent of mast cells or other hematopoietic cells and may result from actions on peripheral neurons.These results demonstrate that the histamine H(4) receptor is involved in pruritic responses in mice to a greater extent than the histamine H(1) receptor.Histamine H(4) receptor antagonists may have therapeutic utility for treating chronic pruritic diseases in humans where histamine H(1) receptor antagonists are not effective.