Ruppin H
Department of Medicine, University of Erlangen-Nürnberg, West Germany.
Aliment Pharmacol Ther. 1987 Jun;1(3):179-90. doi: 10.1111/j.1365-2036.1987.tb00617.x.
The synthetic opioid, loperamide, reduces stool weight, frequency of bowel movements, urgency and faecal incontinence in acute and chronic diarrhoea. In man, the mechanism of action of loperamide is primarily the retardation of small-intestinal transit, and the stimulation of anal sphincter pressure and of faecal continence. This mechanism increases mucosal contact time, allowing more complete absorption of electrolytes and water. Studies in animals have demonstrated inhibitory effects of opiates and opioids, including loperamide, on fluid and electrolyte secretion induced by various secretagogues. By comparison, opiates have smaller if any antisecretory or pro-absorptive actions in man. The discrepancies between the results obtained in animal and human experiments are most certainly due to the large differences between drug doses used. Besides its opiate-receptor binding and stimulating activity, loperamide also behaves as a calcium-calmodulin antagonist and as a calcium channel blocker. These two other mechanisms might contribute to loperamide's antidiarrhoeal activity. Loperamide is more effective and safer than other opiates or opioid drugs in the treatment of both infantile and adult diarrhoea of various causes, although adequate fluid and electrolyte replacement remain the prime need.
合成阿片类药物洛哌丁胺可减轻急性和慢性腹泻时的粪便重量、排便频率、便急及大便失禁症状。在人体中，洛哌丁胺的作用机制主要是延缓小肠转运，并刺激肛门括约肌压力及大便节制。该机制可增加黏膜接触时间，使电解质和水分能更充分地被吸收。动物研究表明，包括洛哌丁胺在内的阿片类药物对多种促分泌剂诱导的液体和电解质分泌具有抑制作用。相比之下，阿片类药物在人体中的抗分泌或促吸收作用即便有也较小。动物实验和人体实验结果的差异很可能是由于所用药物剂量差异巨大所致。除了其阿片受体结合及刺激活性外，洛哌丁胺还表现为钙调蛋白拮抗剂和钙通道阻滞剂。这另外两种机制可能有助于洛哌丁胺的止泻活性。在治疗各种原因引起的婴幼儿及成人腹泻方面，洛哌丁胺比其他阿片类或阿片样药物更有效且更安全，不过充分补充液体和电解质仍然是首要需求。
