期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 502, 期 3, 页码 233-237出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2004.09.010
关键词
chloroquine; malaria; pruritus; kappa opioid receptors
资金
- NIDA NIH HHS [T32DA07237, DA13429] Funding Source: Medline
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. (C) 2004 Elsevier B.V. All rights reserved.
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