title: Structure activity relationships in the pruritogenicity of chloroquine and amodiaquine metabolites in a dog model.
abstract: Using a presumptive animal model of the pruritus produced by chloroquine or amodiaquine in patients with malaria, the ability of mono de-ethylated chloroquine, chloroquine, mono de-ethylated amodiaquine, bi-de-ethylated amodiaquine and normal saline (placebo) to be differentiated in their pruritogenic potentials were determined. The six-hour totals of the visually-monitored pruritic activity showed that the mono de-ethylated chloroquine was no more pruritogenic than placebo (normal saline) and sedated the animals, unlike the mono-de-ethylated and the bi-de-ethylated amodiaquine metabolites which retained the known pruritogenic activity of their parent compound. It is concluded that 4-aminoquinolines with a simple aliphatic side group, like chloroquine, on losing an ethyl group (de-alkylation) have a significant reduction in the pruritogenic effect, but with a more complex aromatic side group, like amodiaquine, even the loss of both ethyl groups does not appreciably decrease their pruritogenic qualities. Thus, the dog model is apparently sensitive enough to be used as a biological animal screen for pruritogenic potentials among quinoline antimalarial drug candidates, and for structure-activity relationship studies in pruritus research.
authors.affiliation: Department of Pharmacology and Toxicology, College of Medical Sciences, University of Benin, Nigeria.
authors.forename: N G
authors.initials: NG
authors.lastname: Osifo
mesh_terms: D000655:Amodiaquine / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002738:Chloroquine / Q000737:chemistry; D003640:Dealkylation; D004285:Dogs; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D011537:Pruritus / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D000655:Amodiaquine; D002738:Chloroquine