Studies with enterotoxigenic microorganisms: effects of candidate antidiarrhoeals in experimental animals in vivo.

Chlorpromazine or aspirin alone, when given to rats parenterally, reduced intestinal fluid secretion induced by cell-free preparations of enterotoxigenic organisms including Escherichia coli, Aeromonas hydrophila, Staphylococcus pyogenes, and Salmonella typhimurium. A combination of chlorpromazine-aspirin given parenterally caused much more marked reduction of fluid secretion. Indomethacin also had significant antisecretory effects against a range of bacterial enterotoxins, while loperamide was effective against heat-labile toxin (LT)-positive E. coli and A. hydrophila. Nicotinamide increased net fluid absorption in the presence of E. coli LT, A. hydrophila, and S. typhimurium. Of the adsorbents tested, aluminum hydroxide showed a positive effect only with E. coli LT and A. hydrophila, while cholestyramine affected net fluid flux only with E. coli ST (heat-stable toxin). Charcoal was effective against all microorganisms tested but only when premixed with the perfusate before the experiments. Aspirin and chlorpromazine probably act at multiple sites to decrease intestinal secretion, and the combination of low doses of these drugs with possibly different sites of action may have advantages over a single agent used in high dosage.