Hurwitz A, Sztern M I, Looney G A, Ben-Zvi Z
Department of Medicine, University of Kansas Medical Center, Kansas City 66160-7320.
Life Sci. 1994;54(22):1687-98. doi: 10.1016/0024-3205(94)00609-1.
Loperamide effects on hepatobiliary function, analgesia and gut transit were studied in mice. Varying doses of the antidiarrheal drug, loperamide, were administered to mice by intracerebroventricular, intravenous, subcutaneous and intragastric routes. Gut motility was determined by intestinal transit of India ink, analgesia by warm water tail flick latency, and hepatobiliary function by retention of the anionic dye, sulfobromophthalein in plasma and liver. When given by all routes at modest doses, loperamide slowed intestinal transit. Analgesia, a centrally mediated opiate effect, was only detected after intracerebroventricular or subcutaneous loperamide at high, near-toxic doses. Elevations of plasma and liver sulfobromophthalein were noted at routes and doses which slowed gut transit, well below those needed for analgesia. Intragastric loperamide at one fortieth its LD50 caused marked elevation of sulfobromophthalein levels and gut slowing, but no analgesia. Sulfobromophthalein elevation and gut slowing by intragastric loperamide were not affected by spinal cord transection but were reversed by naltrexone, an opiate antagonist. Non-toxic doses of loperamide slow gut transit and modify hepatobiliary function in mice by opiate actions at peripheral sites.
在小鼠中研究了洛哌丁胺对肝胆功能、镇痛和肠道转运的影响。通过脑室内、静脉内、皮下和胃内途径给小鼠施用不同剂量的止泻药洛哌丁胺。通过印度墨水在肠道中的转运来测定肠道运动，通过温水甩尾潜伏期来测定镇痛效果，通过血浆和肝脏中阴离子染料磺溴酞钠的潴留来测定肝胆功能。当以适度剂量通过所有途径给药时，洛哌丁胺会减缓肠道转运。镇痛是一种中枢介导的阿片样作用，仅在高剂量、接近中毒剂量的脑室内或皮下注射洛哌丁胺后才检测到。在减缓肠道转运的给药途径和剂量下，血浆和肝脏中的磺溴酞钠水平会升高，远低于产生镇痛所需的剂量。胃内给予洛哌丁胺其半数致死量的四十分之一会导致磺溴酞钠水平显著升高和肠道运动减慢，但无镇痛作用。胃内给予洛哌丁胺导致的磺溴酞钠水平升高和肠道运动减慢不受脊髓横断的影响，但可被阿片拮抗剂纳曲酮逆转。无毒剂量的洛哌丁胺通过在外周部位的阿片样作用来减缓小鼠的肠道转运并改变肝胆功能。
