A novel compound that might lead to an inexpensive, easy-to-take treatment for diarrhea has been discovered by scientists in the laboratory of Ferid Murad, M.D., Ph.D., at The University of Texas Health Science Center at Houston. The compound, a pyridopyrimidine derivative, targets acute secretory diarrhea caused by E. coli and other enterotoxigenic strains of bacteria, which produce toxins that stimulate the linings of the intestines, causing them to secrete excessive fluid, thereby producing diarrhea.
During preclinical tests, the compound was associated with a significant reduction in intestinal fluid secretion in an animal model of bacterial diarrhea. It was also linked to reduced fluid build up during laboratory tests on human colon cells. It caused significant decrease in fluid secretion without apparent toxicity.
This approach to the treatment of enterotoxigenic diarrhea works by interrupting the diarrhea-causing chain of events that occur when bacterial toxins enter the intestinal tract. The compound slows the transmission of information in the epithelial cells lining the intestines. Consequently, the molecular mediators regulating the secretion of salt and fluid in the gut do not get fully activated.
"This newly discovered compound decreases the formation of ever-present cellular messenger molecules, cyclic guanosine monophosphate and cyclic adenosine monophosphate, caused by various bacterial toxins and might prevent or attenuate the intestinal fluid secretion, diarrhea, and dehydration," said Dr. Murad, the senior author of the research paper that appears in the June 16 online edition of PNAS. "While this research looks extremely promising as a preventive or therapeutic intervention in Third World diarrheal disease and travelers' diarrhea, much work remains to be done to move into clinical trials and eventual therapeutic approval."
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