Comparative Drug Response of Sensitive and Resistant Strains of Malarial Parasites Using in vitro Bioassays and Animal Models.
Interim rept. 1 Feb 93-1 Feb 97
CENTRAL DRUG RESEARCH INST LUCKNOW (INDIA)
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No escalation of curative doses of reference drugs chloroquine and primaquine in the simian radical curative models has been recorded over the last 14 years. A shorter 3- dose regimen of WR 238605 for anti-relapse activity has been established which would be operationally more acceptable. In addition this compound as exhibited significant blood-schizontocidal, prophylactic and gametocytocidal activities which can be exploited. A new anti-relapse regimen comprising of WR 238605 plus halofantrine or mefloquine as companion blood schizontocides has been developed for management of chloroquine resistant P. vivax in the field. Cyproheptadine has shown antimalarial action against multidrug resistant P. yoelii nigeriensis. Cyproheptadine also exerts mefloquine resistance reversal action against P. knowlesi. This finding will be useful for treatment of mefloquine resistant cases. In vitro bioassay for evaluation of antimalarials using synchronized P. knowlesi and in vitro model for screening of tissue schizontocidal drugs using P. cynomolgi have been established. An in vitro test for methemoglobin toxicity using mastomys erythrocytes to evaluate toxicity of 8 aminoquinoline agents has been developed.
- Medicine and Medical Research