title: Neurokinin-1 receptor antagonist orvepitant is an effective inhibitor of itch-associated response in a Mongolian gerbil model of scratching behaviour.
abstract: Data suggest that substance P could play an important role in pruritus, and therefore, blockade of the neurokinin (NK)-1 receptor might be antipruritic. Thus, we explored in the Mongolian gerbil the effect on scratching behaviour, induced by intra-dermal injection of the NK-1 receptor-specific agonist GR73632, of oral administration of the NK-1 receptor antagonist orvepitant. Orvepitant at all doses tested (0.1-10 mg/kg p.o.) produced a profound inhibition of GR73632 (30 nmol i.d.) induced hindlimb scratching; the minimum effective dose of orvepitant in this model was identified as ≤0.1 mg/kg. The data generated supported the proposition that the antipruritic potential of orvepitant should be evaluated in clinical trials.
authors: NeRRe Therapeutics Ltd, Stevenage Bioscience Catalyst, Stevenage, UK.
authors: Michael K
authors: MK
authors: Trower
authors: Amy
authors: A
authors: Fisher
authors: Neil
authors: N
authors: Upton
authors: Emiliangelo
authors: E
authors: Ratti
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000982:Antipruritics / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy*; D013373:Substance P / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000982:Antipruritics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; C068032:GR 73632; D013373:Substance P; C584555:orvepitant
keywords: GR73632; gerbil; itch; neurokinin-1; orvepitant; pruritogen; pruritus; scratch; substance P; tachykinin