title: Characterization and Validation of a Canine Pruritic Model.
abstract: Preclinical Research The mechanisms mediating canine pruritus are poorly understood with few models due to limited methods for inducing pruritus in dogs. Chloroquine (CQ) is a widely used antimalarial drug that causes pruritus in humans and mice. We have developed a canine model of pruritus where CQ reliably induced pruritus in all dogs tested following intravenous administration. This model is presently being used to test antipruritic activity of drug candidate molecules. This publication has been validated in a blinded cross-over study in eight beagle dogs using the reference standards, oclacitinib and prednisolone, and has been used to test a new compound, norketotifen. All compounds reduced CQ-induced pruritus in the dog. The sensitivity of the model was demonstrated using norketotifen, which at three dose levels, dose-dependently, inhibited scratching events compared with placebo.
authors.affiliation: Bridge Pharma Inc., 902 Contento Street, Sarasota, FL, USA.
authors.forename: Gunnar A K
authors.initials: GA
authors.lastname: Aberg
authors.affiliation: Nucro-Technics, Department of Toxicology, 2000 Ellesmere Road, Scarborough, ON, Canada.
authors.forename: Nada
authors.initials: N
authors.lastname: Arulnesan
authors.affiliation: Nucro-Technics, Department of Toxicology, 2000 Ellesmere Road, Scarborough, ON, Canada.
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Bolger
authors.affiliation: Bridge Pharma Inc., 902 Contento Street, Sarasota, FL, USA.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Ciofalo
authors.affiliation: CroToxPath Consulting Inc., 1920 Ellesmere Rd, Scarborough, ON, Canada.
authors.forename: Kresimir
authors.initials: K
authors.lastname: Pucaj
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects*; D000982:Antipruritics / Q000008:administration & dosage* / Q000627:therapeutic use; D002738:Chloroquine / Q000009:adverse effects*; D018592:Cross-Over Studies; D004283:Dog Diseases / Q000188:drug therapy* / Q000209:etiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007665:Ketotifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000378:metabolism; D011537:Pruritus / Q000188:drug therapy* / Q000209:etiology / Q000662:veterinary; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D000982:Antipruritics; D011743:Pyrimidines; D013449:Sulfonamides; C578473:norketotifen; D002738:Chloroquine; C588062:oclacitinib; D011239:Prednisolone; D007665:Ketotifen
keywords: antipruritic drugs; canine; pruritis; testing