The role of histamine H1, H2, H3 and H4 receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and ‘itch’ assessed by quantifying the scratching evoked. Histamine (0.03–80 μmol), histamine‐trifluoromethyl‐toluidine (HTMT, H1 agonist, 0.002–2 μmol), clobenpropit (H4 agonist, H3 antagonist, 0.002–0.6 μmol) and to a lesser extent imetit (H3/H4 agonist, 0.03–3 μmol) all induced dose‐dependent scratching. Dimaprit (H2 agonist, 0.04–40 μmol) did not cause scratching. Mepyramine (H1 antagonist, 20 mg kg−1, i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H3 or H4 agonists. Thioperamide (H3/H4 antagonist, 20 mg kg−1, i.p.) reduced scratching induced by histamine, H3 and H4 agonists, but not that caused by HTMT. The non‐sedating H1 antagonist, terfenadine, also significantly reduced the scratching induced by the H1 agonist, HTMT. Cimetidine (H2 antagonist, 20 mg kg−1, i.p.) did not affect histamine‐induced scratching. These results indicate that activation of histamine H4 receptors causes itch in mice, in addition to the previously recognised role for H1 receptors in evoking itch. Histamine H4 receptor antagonists therefore merit investigation as antipruritic agents. British Journal of Pharmacology (2004) 142, 374–380. doi:

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