Studies on the genotoxic and mutagenic potentials of mefloquine

ABSTRACT

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 WP[2] trp and WP[2] 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