Reversal of Enterotoxic Diarrhoea by Anaesthetic and Membrane‐stabilizing Agents

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Abstract
The effect of membrane-stabilizing and sedative drugs on enterotoxic diarrhea was studied in mice. Fluid secretion was induced in ligated loops of the small intestine by challenge with cholera toxin (CT), heat-labile enterotoxin (LT) from Escherichia coli or dibuturyl-cAMP (dB-cAMP). Chlorpromazine, melperone, diazepram, mebumal, ketamine and ethanol all inhibited CT-induced hypersecretion, ED50 being 1.5, 4, 4, 35, 70 and 1500 mg/kg, respectively. The drugs also blocked CT-stimulation of adenylate cyclase, which mediates the action of CT. Concomitant with the antisecretory effect, a sedative effect was induced, as judged by the motility and righting reflex of the animals. Hypersecretion by E. coli LT was also totally blocked by chlorpromazine, diazepam, ketamine and ethanol. The secretion by dB-cAMP, which bypasses adenylate cyclase in its action, was not affected by diazepam and was only partly reversed by chlorpromazine, ketamine and ethanol. The reversal of dB-cAMP-secretion is probably due to enhanced absorption, rather than inhibition of adenylate cyclase. The use of membrane-stabilizing drugs may represent a new principle for pharmacological treatment of diarrhea.