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A review of the morphinomimetic activities of the antidiarrheal drugs loperamide and nufenoxole (SC-27166) is presented. These agents bind, in an agonist manner, to opiate receptor sites of brain and myenteric plexus and probably produce their therapeutic actions and side effects through this receptor. Although both agents produce potent opiatelike effects in the myenteric plexus of the small intestine in vivo, CNS side effects are not seen until very high doses are administered. The narcotic-type abuse potential appears to be low for loperamide and may be even lower for nufenoxole. The marked separation of central and peripheral activities probably results from a differential pattern of absorption and distribution that results in a low concentration of drug at receptor sites in the brain and a high concentration at sites in the myenteric plexus.

journal of the american college of toxicology

Review of the Involvement of Opiate Receptors in Producing the Central and Peripheral Effects Caused by Two New Antidiarrheal Drugs, Loperamide and SC-27166