Loperamide is presently used more often as an antidiarrheal drug than as an analgesic, and
it is also included in the list of over-the-counter drugs because of its insignificant action on
the CNS. It reduces intestinal smooth muscle tone and motility as a result of binding to
intestinal opiate receptors. It is used for symptomatic treatment of severe and chronic diarrhea of various origins. The most popular synonym for loperamide is imodium.
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ChEBI: A synthetic piperidine derivative, effective against diarrhoea resulting from gastroenteritis or inflammatory bowel disease.
World Health Organization (WHO)
Loperamide, an inhibitor of intestinal peristalsis, was introduced
in 1975 for the treatment of acute and chronic diarrhoea. In many countries its use
was discouraged in young children. In late 1989, treatment of infants in Pakistan
was associated with 19 cases of paralytic ileus, 6 of which have been fatal. This
has subsequently led the major manufacturer to withdraw all drop formulations of the drug worldwide as well as the lower dose syrup forms from countries where
there is a programme for the control of diarrhoeal diseases. The WHO Control of
Diarrhoeal Diseases Programme recommends that loperamide should not be used
in children below five year of age.
(Reference: (LJJ) Letter to WHO from Johnson & Johnson, , , 21 June 1990)
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Loperamide (Imodium) is a 4-phenylypiperidine with amethadone-like structure attached to the piperidine nitrogen. It acts as an antidiarrheal by directly binding tothe opiate receptors in the gut wall. Loperamide inhibitsacetylcholine and prostaglandin release, decreasing peristalsisand fluid secretion thus increasing the GI transit time andreducing the volume of fecal matter.Loperamide is sufficiently lipophilic to cross the blood-brain barrier, yet itdisplays no CNS-opioid effects. The reason for this is that itis actively pumped out of the brain via the P-glycoproteinpump (MDR1). Knockout mice with the P-glycoproteinpump genetically removed were given radiolabeled loperamideand sacrificed 4 hours later. The [3H]loperamideconcentrations were measured and compared with wild-typemice. A 13.5-fold increase in loperamide concentration wasfound in the brain of the knockouts. In addition, the micelacking the P-glycoprotein pump displayed pronouncedsigns of central opiate agonism. Loperamide is availableas 2-mg capsules for treatment of acute and chronic diarrhea.Recommended dosage is 4 mg initially, with 2 mgafter each loose stool for a maximum of 16 mg/d.
