EVALUATION OF EXTRACTS OF MORINDA LUCIDA AND OTHER DRUGS FOR ANTIMALARIA ACTIVITY
Abstract
The impact of the problem of drug resistance on the capacity to provide adequate treatment for malaria is becoming more marked as more countries try to provide treatment facilities for their entire population. The need for research to discover new drugs with novel mechanisms of action and to find ways of preventing or delaying the development of drug resistance has become increasingly urgent (WHO,1984). Thus, this study was undertaken: to evaluate extracts of M.lucida leaves, stem bark and root bark for antimalarial activity, to monitor the sensitivity of Plasmodium Falciparum (which is the most lethal malarial parasite in humans) to chloroquine, amodiaquine, quine and mefloquine/sulfadoxine/pyrimethamine, and to compare the antimalarial activities of quine, cinchonine, quinidine and their combination, LA 40221. This was done by studying the effect of M.lucida on P.berghei in mice and P.falciparum in humans. Sensitivity studies were done using both in vivo and in vitro methods (WHO,1986a) which were also used for comparing the cinchona alkaloids against P.berghei and P.falciparum. The extracts of the leaf and stem bark of M.lucida were found to have antimalarial activity. Except for a small subpopulation of chloroquine resistance parasites, P.falciparum was observed to be sensitive to chloroquine, amodiaquine quine and MSPs, but resistant to mefloquine in vitro even though this drug has not yet been released in Nigeria. However, intrinsic resistance of malaria parasites to drugs has been accepted as possible (WHO, 1986b). Studies on the cinchona alkaloids showed that the combinations LA 40221 is more active than quinidine and cinchonine and much more so than quinidine and cinchonine and much more so than quinine against P.berghei in vitro, but changed places with quinidine against P.falciparum in vitro. It was also more active than quinine against P.falciparum in vivo and is therefore a drug combination that is potentially useful as is quinidine in malaria chemotherapy. It is concluded that the full dose of chloroquine should be administered in malaria to delay resistance: and that M.lucida and LA 40221 merit further study.
Description
A Thesis in the Department of Pharmacology and Therapeutics, submitted to the College of Medicine, in partial fulfillment of the requirements for the degree of Doctor of Philosophy of the University of Ibadan.