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. Strategic evaluation of several pharmacological agents in combination with chloroquine to enhance the sensitivity of the latter against resistant parasites has been documented in several studies. However no attempts have been directed to monitor the efficacy of such biological response modifiers for reversing the resistance to halofantrine. In the present study the comparative efficacy of a total of 22 pharmacological agents representing diverse categories including antihistamines, antidepressants, calcium channel blockers, neuroleptics etc. has been determined in combination with halofantrine against halofantrine resistant Plasmodium yoelii nigeriensis. Results show significant potentiation of the efficacy of halofantrine when administered concurrently with histamine H1 receptor antagonists cyproheptadine and ketotifen. Combination with pheniramine, amitriptyline, verapamil and penfluridol also produced moderate degree of potentiation which was well marked during the early phase of progression of parasitaemia.