The Enkephalinase Inhibitor, Acetorphan, in Acute Diarrhoea: A Double-Blind, Controlled Clinical Trial versus Loperamide

Abstract

The antidiarrhoeal properties of acetorphan, an inhibitor of enkephalinase (EC 3.4.24.11) that prevents endogenous enkephalin degradation, and loperamide, a mu opiate receptor agonist, were compared. The double-blind study included 69 patients with acute diarrhoea of presumed infectious origin, allocated at random to two parallel groups. Acetorphan and loperamide were both rapidly and similarly effective, diarrhoea resolving in both cases in nearly 2 days. With acetorphan, however, abdominal distension vanished significantly more rapidly, and reactive constipation was less frequent (8% versus 31% with loperamide). These differences can be accounted for by the distinct mechanisms of antidiarrhoeal activity of the two drugs—that is, primary antitransit effect for loperamide and antisecretory activity for acetorphan.

Key Words:

• Acetorphan
• acute diarrhoea
• constipation
• enkephalinase (EC 3.4.24.11)
• intestinal antisecretory activity
• intestinal transit
• mu opioid agonists