Interaction between chloroquine and diverse pharmacological agents in chloroquine resistant Plasmodium yoelii nigeriensis?

The effect of a number of pharmacological agents on the enhancement of anti malarial activity of chloroquine was evaluated against chloroquine resistan t line of Plasmodium yoelii nigeriensis (N-67). The response after combinat ion therapy was monitored on the basis of alteration in the course of paras itaemia, the extension of mean survival time and the percent cure rate in d ifferent groups. The study was designed to compare the in vivo efficacy of a number of resistance modulating agents found effective in several in vitr o studies against chloroquine resistant P. falciparum isolates. Based on th eir efficacy in this rodent model, the response of combination of chloroqui ne with agents representing diverse chemical moieties has been categorised as curative, moderately active and inactive. Out of the 22 agents evaluated , only cyproheptadine-chloroquine combination produced curative response. K etotifen, azatadine, pheniramine. amitriptyline, fluoxetine, verapamil. pen fluridol and trifluoperazine demonstrated moderate activity while loratadin e, terfenadine, promethazine, ranitidine, nifedipine, diltiazem, chlorproma zine, amiodarone, tamoxifen, dipyridamol, propranolol. acyclovir and amanti dine were inactive. The study advocates the suitability of proposed rodent model to shortlist potential resistance reversal agents. (C) 2000 Elsevier Science B.V. All rights reserved.