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The NK 1 receptor antagonist aprepitant attenuates NK 1 agonist‐induced scratching behaviour in the gerbil after intra‐dermal, topical or oral administration
Author(s) -
Costantini Vivian J. A.,
Corsi Mauro,
Dünstl Georg,
Bettelini Letizia,
Zonzini Laura,
Gerrard Philip
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12656
Subject(s) - aprepitant , gerbil , scratching , agonist , pharmacology , nk1 receptor antagonist , antagonist , receptor antagonist , medicine , systemic administration , receptor , in vivo , substance p , antiemetic , vomiting , biology , neuropeptide , physics , microbiology and biotechnology , ischemia , acoustics
Abstract Experiments were conducted to develop a model to study the effect of oral and topical administration of the NK 1 receptor antagonist aprepitant, on scratching behaviour in gerbils. The gerbil was selected due to its relevance for human NK 1 receptor pharmacology. Intradermal injection of a specific NK 1 receptor agonist GR 73632 (100 nmol/100 µl) at the rostral back of gerbils produced scratching of the injection site. This could be attenuated by intradermal co‐administration of a selective NK 1 receptor antagonist aprepitant (30–100–300 nmol), demonstrating the role of dermal NK 1 receptor in elicitation of scratching behaviour. Likewise, scratching was attenuated by oral (0.3–3–30 mg/kg) or topical application (0.01–0.1–1% w/v) of aprepitant and pharmacokinetic analysis of aprepitant levels in brain, blood and skin supported that efficacy of topically applied aprepitant was due to dermal rather than central target engagement. In conclusion, we showed that NK 1 agonist‐induced scratching in the gerbil can be reversed by systemic and topical administration of aprepitant. This test system may provide a useful model for the in vivo assessment of putative antipruritic agents.