The pharmacology of SC-27166: a novel antidiarrheal agent.

SC-27166 is the result of continuing efforts to discover selective and orally active antidiarrheal agents. SC-27166, which is chemically unrelated to opiates or neuroleptics, possesses potent constipating and antidiarrheal activity in several animal models. Tolerance to the constipating actions of SC-27166 did not develop in mice. On the other hand, gut tolerance rapidly developed to morphine sulfate and loperamide. The basic mechanism of the antidiarrheal action of SC-27166 is a consequence of increased intestinal circular muscle contractile activity. Supportive pharmacological studies indicated that SC-27166 has equivocal analgesia in mice which is manifested at near toxic dose levels. SC-27166 was also evaluated for potential dependence liability in morphine abstinence-induced jumping in mice. The abstinence-induced jumping was suppressed to a far lesser extent by SC-27166 than by either loperamide or diphenoxylate at equal doses. SC-27166 was also devoid of anticbholinergic activity. When compared with the reference standards morphine and diphenoxylate, these pharmacological studies indicated that SC-27166 has a high degree of separation of undesirable central nervous system actions from its antidiarrheal properties and may have important therapeutic potential.