ABSTRACT
Opium has been employed historically for the alleviation of dysentery and diarrheal disorders [1]. Although the principal opiate alkaloids morphine and codeine were chemically isolated in the 19th century and employed as antidiarrheal medications, the worldwide use of antidiarrheal preparations of opium and opium tinctures, such as paregoric, has continued into the 21st century. With the development of many synthetic and semisynthetic opioid drugs in the twentieth century, newer antidiarrheal opioids have been identified and introduced into modern medical practice. These include the peripherally acting opioid agonists diphenoxylate and loperamide, which were first shown in the 1970s to be clinically effective in limiting chronic diarrhea [2,3]. Inhibitors of neutral endopeptidase (EC 3.4.24.11), such as the thiorphan derivative acetorphan, have been found to possess antidiarrheal efficacy after oral administration that may be comparable with that of loperamide in decreasing acute watery diarrheas in children and adults [4,5]. By inhibiting this enzyme, acetorphan diminishes the degradation of one family of endogenous opioid peptides, the enkephalins, in the intestinal
wall. Opioid antidiarrheal drugs are also used in the treatment of diarrheapredominant inflammatory bowel disease [6] and to increase intestinal transit time in the short bowel syndrome [7].
