Niemegeers C J, McGuire J L, Heykants J J, Janssen P A
J Pharmacol Exp Ther. 1979 Sep;210(3):327-33.
Three synthetic antidiarrheals, diphenoxylate, loperamide and SC 27166, and two narcotics, morphine and codeine, were evaluated in rats by the intravenous 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. Intravenously, all five 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 central nervous system 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 hr = 1.81 mg/kg) and most specific (relative antidiarrheal specificity, 8 hr greater than or equal to 88) and having the greatest relative safety margin (8 hr = 102).
通过静脉注射和口服途径，在大鼠身上对三种合成止泻药（地芬诺酯、洛哌丁胺和SC 27166）以及两种麻醉药（吗啡和可待因）的止泻、类阿片样和急性毒性作用的特异性和持续时间进行了评估。蓖麻油试验、甩尾试验和急性毒性试验中的活性用于确定相对止泻特异性和相对安全范围。对动物和临床数据的分析表明，这些试验是临床效用和特异性的优秀指标。静脉注射时，所有五种药物都能产生类阿片样中枢作用，只有洛哌丁胺和SC 27166在接近中毒剂量时才会出现。口服洛哌丁胺和SC 27166时，它们没有类阿片样中枢神经系统活性。口服洛哌丁胺后的血浆水平分析表明，该药物达不到足以产生类阿片样中枢作用的浓度。所有药物通过口服途径都是有效的止泻药，其中洛哌丁胺效力最强（半数有效量=0.15毫克/千克）、作用时间最长（8小时半数有效量=1.81毫克/千克）、特异性最高（相对止泻特异性，8小时大于或等于88）且相对安全范围最大（8小时=102）。
