Drug Resistance in Trypanosomes; Selective Interference With Trypanocidal Action

Abstract

Selective reversal of the trypanocidal action of carboxylated arsenicals by p-aminobenzoic acid and of melaminyl arsenicals and diamidines by melamine has been demonstrated in vivo and in vitro. The structural specificity of these reversal phenomena is high, and suggests preferential adsorption of the antagonist during a reversible primary drug fixation stage. Thiols antagonize neutral, carboxylated and melaminyl aromatic arsenicals equally, but not diamidines; p-aminobenzoic acid antagonism is specific for carboxylated arsenicals, and melamine antagonizes only the melaminyl arsenicals and the diamidines. These reversals reflect the pattern of crossresistance behaviour and suggest that cellular structures associated with a reversible stereospecific drug adsorption phase are modified during the development of resistance.