Antidiarrheal and central nervous system activities of SC-27166 (2-[3 - 5 - methyl - 1, 3, 4 - oxadiazol - 2 - yl) - 3, 3 - diphenylpropyl] - 2 - azabicyclo [2.2.2]octane), a new antidiarrheal agent, resulting from binding to opiate receptor sites of brain and myenteric plexus.

Pharmacological studies were performed to investigate the interaction of SC-27166 (2-[3-(5-methyl-1,3,4--oxadiazol-2-yl)-3,3-diphenylpropyl]-2-azabicyclo[2.2.2]octane), a new antidiarrheal agent, with opiate receptor sites in vitro and in vivo. Morphine, loperamide and SC-27166 inhibited the binding of [3H]naloxone to homogenates of guinea-pig brain and myenteric plexus and the inhibition was diminished in the presence of 100 mM Na+. Unlike that of morphine and [3H]naloxone itself, the binding of loperamide and SC-27166 was complex and Scatchard plots indicated the presence of low and high affinity sites for both compounds. Morphine, loperamide and SC-27166 inhibited the contractions of electrically driven longitudinal muscle from guinea-pig ileum and naloxone antagonized these effects. In the anesthetized dog, i.v. administration of morphine and SC-27166 enhanced the contractile activity of circular muscle in proximal and distal duodenum and distal ileum but duodenal longitudinal muscle was relaxed; these effects were completely reversed by subsequent administration of naloxone. In the rat, p.o. administration of loperamide and SC-27166 inhibited intestinal propulsion at doses considerably lower than were necessary to produce activity in the hot plate test; this specificity of action was not seen with morphine. In the rat, p.o. administration of loperamide and SC-27166 inhibited diarrhea at doses considerably lower than were necessary to produce withdrawal symptoms. The authors concluded that both loperamide and SC-27166 are specific antidiarrheal agents that produce both their central and antidiarrheal effects by binding to opiate receptor sites.