Kappa opioid agonists suppress chloroquine-induced scratching in mice.
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.
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA. sinan@temple.edu
Saadet
S
Inan
Alan
A
Cowan
D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002738:Chloroquine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D011537:Pruritus / Q000139:chemically induced / Q000517:prevention & control*; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology
D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa; D002738:Chloroquine