Modulation of halofantrine resistance after coadministration of halofantrine with diverse pharmacological agents in a rodent malaria model

The declining efficacy of antimalarial drugs against Plasmodium falciparum strains has been reported from several endemic regions of the world. Strate gic evaluation of several pharmacological agents in combination with chloro quine to enhance the sensitivity of the latter against resistant parasites has been documented in several studies. However no attempts have been direc ted to monitor the efficacy of such biological response modifiers for rever sing the resistance to halofantrine. In the present study the comparative e fficacy of a total of 22 pharmacological agents representing diverse catego ries including antihistamines, antidepressants, calcium channel blockers, n euroleptics etc, has been determined in combination with halofantrine again st halofantrine resistant Plasmodium yoelii nigeriensis, Results show signi ficant potentiation of the efficacy of halofantrine when administered concu rrently with histamine H-1 receptor antagonists cyproheptadine and ketotife n, Combination with pheniramine, amitriptyline, verapamil and penfluridol a lso produced moderate degree of potentiation which was well marked during t he early phase of progression of parasitaemia. (C) 2000 Elsevier Science In c. All rights reserved.