title: Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo.
abstract: Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical application of the reversal phenomenon.
authors.affiliation: Department of Pharmacology and Therapeutics, Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria. akinsowunmi@hotmail.com
authors.forename: Akintunde
authors.initials: A
authors.lastname: Sowunmi
authors.forename: Grace O
authors.initials: GO
authors.lastname: Gbotosho
authors.forename: Christian T
authors.initials: CT
authors.lastname: Happi
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Adedeji
authors.forename: Olayinka M
authors.initials: OM
authors.lastname: Bolaji
authors.forename: Fatai A
authors.initials: FA
authors.lastname: Fehintola
authors.forename: Babasola A
authors.initials: BA
authors.lastname: Fateye
authors.forename: Ayoade M J
authors.initials: AM
authors.lastname: Oduola
mesh_terms: D000293:Adolescent; D000655:Amodiaquine / Q000008:administration & dosage*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage*; D002744:Chlorpheniramine / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics
chemical_list: D000962:Antimalarials; D006634:Histamine H1 Antagonists; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D000655:Amodiaquine; D002744:Chlorpheniramine; D002738:Chloroquine