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Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy
Authors:Willem S. Lexmond  Paul A. Rufo  Edda Fiebiger  Wayne I. Lencer
Affiliation:Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, ; University of California San Diego School of Medicine, UNITED STATES,
Abstract:ResultsTreatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca2+-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90).ConclusionTreatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca2+-dependent agonists as expected, but did not affect Na+-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.
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