Studies on the Genotoxic and Mutagenic Potentials of Mefloquine

Purpose: The detection of mefloquine mutagenicity has not been achieved by the use of Salmonella typhimurium his TA1535, TA1537 as tester strains. With the introduction of improved and more sensitive strains, it is of interest to evaluate the current mutagenic and genotoxic status of the drug. This study presents data on the in-vitro mutagenic and genotoxic potentials of mefloquine hydrochloride clinically used as an antimalarial agent. Method: The mutagenicity potentials was investigated in the Escherichia coli WP2 trp and WP2 uvrA trp tester strains containing the plasmids, pEB017 and pKM101, and the Salmonella typhimurium TA97 containing pKM101. The genotoxicity potential was determined using the microscreen phage-induction assay. Results: The presence of plasmids pEBO17 and pKM101 enhanced the detection of mutagenicity of mefloquine. Microsomal-activated mefloquine unequivocally elicited base-pair substitution mutagenicity. The genotoxicity test indicated that mefloquine was generally not genotoxic but was of the same potential mutagenicity as chloroquine phosphate. Conclusion: Melfloquine hydrochloride exhibits base pair substitution mutagenesis, but not potentially genotoxic, even though it showed concentration dependent cytotoxicity. Its use as a last line antimalarial agent should still be encouraged.