Abstract
Chemotherapy of malaria fever with chloroquine is often associated with generalized pruritus of unknown pathogenesis. This adverse side effect leads to diminished compliance. We report that chloroquine (1.25–40 mg/kg, s.c.) elicits dose-related, compulsive, and vigorous scratching in mice. This frenzied behavior is essentially abolished when the mice are pretreated s.c. or orally with nalfurafine (TRK-820), a centrally penetrating kappa opioid agonist. Peripheral kappa receptors are involved because chloroquine-induced scratching is also antagonized by the peripherally restricted kappa agonist, ICI 204,448: R, S- N-[2-( N-methyl-3,4-dichlorophenylacetamido)-2-(3-carboxyphenyl) ethyl]pyrrolidine. We propose that combination therapy for malaria with chloroquine and a kappa agonist (probably one targeting peripheral receptors) will lead to better treatment compliance because of a reduced incidence of pruritus.
Published Version
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