DISSOCIATION BETWEEN OPIATE-LIKE AND ANTIDIARRHEAL ACTIVITIES OF ANTIDIARRHEAL DRUGS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 210  (3) , 327-333
Abstract
Three synthetic antidiarrheals, diphenoxylate, loperamide and SC 27166 [2-[3-(5-methyl-1,3,4-oxadiazol-2-yl)-3,3-diphenylpropyl]-2-azabicyclo[2,2,2]-octane] and 2 narcotics, morphine and codeine, were evaluated in rats by the i.v. and oral route for specificity and duration of their antidiarrheal, opiate-like and acute toxic effects. The activity in the castor oil test, the tail withdrawal test and the acute toxicity test was used to determine the relative antidiarrheal specificity and relative safety margins. An analysis of animal and clinical data indicate these tests to be excellent indicators of clinical usefulness and specificity. I.v., all 5 agents induced opiate-like central effects, loperamide and SC 27166 at near toxic doses only. When administered orally loperamide and SC 27166 were devoid of opiate-like CNS activity. Analysis of the plasma levels after oral loperamide indicated that this drug does not attain a concentration high enough to induce opiate-like central effects. All agents were effective antidiarrheals by the oral route with loperamide being the most potent (ED50 = 0.15 mg/kg), longest acting (ED50 8 h = 1.81 mg/kg) and most specific (relative antidiarrheal specificity, 8 h .gtoreq. 88) and having the greatest relative safety margin (8 h = 102).