title: The NK1 receptor antagonist aprepitant attenuates NK1 agonist-induced scratching behaviour in the gerbil after intra-dermal, topical or oral administration.
abstract: Experiments were conducted to develop a model to study the effect of oral and topical administration of the NK1 receptor antagonist aprepitant, on scratching behaviour in gerbils. The gerbil was selected due to its relevance for human NK1 receptor pharmacology. Intradermal injection of a specific NK1 receptor agonist GR73632 (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 NK1 receptor antagonist aprepitant (30-100-300 nmol), demonstrating the role of dermal NK1 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 NK1 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.
authors: Center of Drug Design & Discovery, Aptuit s.r.l., Verona, Italy.
authors: Vivian J A
authors: VJ
authors: Costantini
authors: Mauro
authors: M
authors: Corsi
authors: Georg
authors: G
authors: Dünstl
authors: Letizia
authors: L
authors: Bettelini
authors: Laura
authors: L
authors: Zonzini
authors: Philip
authors: P
authors: Gerrard
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000982:Antipruritics / Q000008:administration & dosage*; D000077608:Aprepitant; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005849:Gerbillinae; D006801:Humans; D007271:Injections, Intradermal; D009025:Morpholines / Q000008:administration & dosage*; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000982:Antipruritics; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; C068032:GR 73632; D000077608:Aprepitant; D013373:Substance P
keywords: Itch; NK1 receptor; aprepitant; gerbil; scratching behaviour