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Drug Dev Res ; 76(5): 246-50, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26220424

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.


Subject(s)
Antimalarials/adverse effects , Antipruritics/administration & dosage , Chloroquine/adverse effects , Dog Diseases/drug therapy , Ketotifen/analogs & derivatives , Pruritus/drug therapy , Animals , Antipruritics/therapeutic use , Cross-Over Studies , Dog Diseases/etiology , Dogs , Dose-Response Relationship, Drug , Female , Ketotifen/administration & dosage , Ketotifen/therapeutic use , Male , Prednisolone/administration & dosage , Prednisolone/metabolism , Pruritus/etiology , Pruritus/veterinary , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use
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