title: The pharmacology of SC-27166: a novel antidiarrheal agent.
abstract: 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.
mesh_terms: D000700:Analgesics; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D003248:Constipation / Q000139:chemically induced; D003967:Diarrhea / Q000503:physiopathology; D004157:Diphenoxylate / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D000882:Haplorhini; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D010276:Parasympatholytics; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
chemical_list: D000700:Analgesics; D000930:Antidiarrheals; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D010069:Oxadiazoles; D010276:Parasympatholytics; D009270:Naloxone; D004157:Diphenoxylate; D009020:Morphine