Pruritus Scratching Model
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Melior has evaluated several agents associated with either histamine-dependent or histamine-independent pruritus (scratching; pruritus dermatitis).
Examples of non-histamine dependent pruritus-inducing agents include chloroquine, oxazolone, DNFB, imiquimod, and MC903. Each is associated with characteristic differences and work through different mechanisms.
Examples of histamine dependent itch include mast cell degranulating agents such as the polymer 48/80. Although histamine dependent pruritus is effectively served with diphenhydramine (Benadryl®), there remains an unmet medical need for agents to treat non-histamine dependent itch.
Chloroquine (an anti-malarial) induces an itching response that is mediated via non-histaminergic mechanisms. Direct injection of chloroquine into the back induces itch and a scratching response in mice. When itching elicits the need to scratch, the tissue gets damaged which initiates the release of inflammatory markers, perpetuating the itch and creating a cycle.
This study validates the anti-itch effects of U-50,488 in a murine chloroquine-induced itch model.
Depending upon the pruritus-inducing agent used, these studies can range from 1 day to 3 weeks. While the chloroquine model described above is a one-day model, other agents such as oxazolone, DNFB, imiquimod, and MC903 require 7 days and longer for pruritus to be established.