LOPERAMIDE - SURVEY OF STUDIES ON MECHANISM OF ITS ANTIDIARRHEAL ACTIVITY

In castor oil challenged rats, low doses of loperamide inhibit diarrhe a and normalize intestinal propulsion. Unlike other opioids, loperamid e is devoid of central opiate-like effects, including blockade of inte stinal propulsion, up to the highest subtoxic oral dose. Nevertheless, the antidiarrheal action of loperamide can be considered to be mu-opi ate receptor mediated, only a few in vitro effects at rather high conc entrations being not naloxone-reversible. There is little evidence tha t interactions with intestinal opiate receptors directly change epithe lial cell function. When secretory stimuli increase mucosal tension, h owever, loperamide may reverse the elevated hydrostatic tissue pressur e that opposes normal absorption. This antisecretory effect at the muc osal level is accompanied by motor effects when loperamide reaches the myenteric mu-opiate receptors. At therapeutic doses for the treatment of acute diarrhea, it is likely that the mucosal effect prevails.