Disease relevance of loperamide

• Eight of the loperamide-treated subjects experienced constipation compared with one in the bismuth subsalicylate-treated group; otherwise, there was no difference in minor side effects experienced between both treatment groups [1].
• Loperamide to diagnose Cushing's syndrome [2].
• Toxic megacolon associated with loperamide therapy [3].
• No significant prolongation of disease was seen in subjects with shigellosis treated with loperamide [1].
• Only one patient was hospitalized for failure to respond to loperamide, and no major toxicity was associated with loperamide use [4].

Psychiatry related information on loperamide

• The aim of these experiments was to evaluate simultaneously the effects of a synthetic opiate, loperamide, on motor activity and transport in the human intestine [5].
• Sensory thresholds and the recto/pouch-anal inhibitory reflex were not influenced by loperamide treatment [6].
• Misuse of loperamide in anxiety disorder patients [7].

High impact information on loperamide

• A single dose of sulfamethoxazole-trimethoprim was also efficacious (28 vs 59 hours), but loperamide alone was significantly effective only when treatment failures were treated with antibiotics (33 vs 58 hours) [8].
• Subjects treated with the combination had the shortest average duration of diarrhea compared with the placebo group (1 hour vs 59 hours), took the least amount of loperamide after the loading dose (3.8 mg), and had the shortest duration of diarrhea associated with fecal leukocytes or blood-tinged stools (4.5 hours) [8].
• A pilot toxicity study with oral loperamide showed that this peripherally acting antidiarrheal agent gains potent opiatelike activity in the central nervous system of mdr1a (-/-) mice. mdr1a (-/-) mice also showed increased sensitivity to neurolepticlike side effects of oral domperidone [9].
• Tissue distribution studies demonstrated that the relative brain penetration of radiolabeled ondansetron and loperamide (and their metabolites) is increased four- and sevenfold, respectively, in mdr1a (-/-) mice [9].
• Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla ileal mucosa. Selective inhibition by loperamide [10].

Chemical compound and disease context of loperamide

• CONCLUSIONS: Loperamide decreases the number of unformed stools and shortens the duration of diarrhea in dysentery caused by Shigella in adults treated with ciprofloxacin [11].
• Conversely, when 12 normal volunteers took loperamide capsules sufficient to cause symptomatic constipation and to prolong mean transit-time from 48 to 103 hours, the deoxycholic acid pool increased from 0.40 +/- 0.24 to 0.57 +/- 0.17 g (p = 0.008) [12].
• In the present study we found that acute oral administration of loperamide resulted in 50% inhibition of postprandial trypsin and bilirubin output in patients with short bowel syndrome [13].
• RESULTS: Loperamide produced no respiratory depression when administered alone, but respiratory depression occurred when loperamide (16 mg) was given with quinidine at a dose of 600 mg (P < .001) [14].
• In six patients with Cushing's disease and one patient with secondary adrenal insufficiency due to hypothalamic failure, neither basal ACTH and cortisol levels nor CRH-stimulated levels were influenced by loperamide [15].

Biological context of loperamide

• When loperamide-pretreated vesicles were incubated with 2 microM calcium (free concentration) plus 5 microM calmodulin for 1 h at 5 degrees C, complete inhibition of the stimulatory effect of loperamide on Cl-/OH- antiport and Na+/Cl- cotransport was observed [16].
• After application of loperamide (12 mg), cyclically recurring migrating motor complexes in the small intestine occurred at a significantly higher frequency than after application of placebo [5].
• The area under the gastric emptying curve, a potentially more sensitive parameter for measuring gastric emptying, was significantly increased in the group receiving 12 and 18 mg of lidamidine (p less than 0.05) compared with the group receiving loperamide or placebo [17].
• Loperamide is a well-established antidiarrhoeal agent with effects on gastrointestinal motility [18].
• Average AUC of diarrhoea (1.9 v 4.5; p=0.09) and average number of loperamide tablets taken (0.4 v 2.6; p=0.002) were reduced in the glutamine arm [19].

Anatomical context of loperamide

• Loperamide increased the transit time in the jejunum but not in the ileum or in the colon [5].
• Influence of loperamide on the internal anal sphincter in the opossum [20].
• Brush border membrane vesicles were incubated with 10 microM loperamide over 4 h at 5 degrees C before the uptake experiments [16].
• The most common medication classes were smooth-muscle relaxants (16 trials), bulking agents (13 trials), prokinetic agents (6 trials), psychotropic agents (7 trials), and loperamide (4 trials) [21].
• Loperamide at 10-30 microM has no effect on intracellular calcium levels alone, but augments calcium levels in cultured cells when SOC channels have been activated [22].

Associations of loperamide with other chemical compounds

• Loperamide, a novel antidiarrheal agent, was compared with diphenoxylate in a double blind crossover study of 23 patients with chronic diarrhea of various etiologies [23].
• The effects of loperamide on net solute and water absorption, and prostaglandin E2 (PGE2) and cholera toxin-induced secretion were studied in the rat jejunum using an in vivo steady-state perfusion technique [24].
• The passive movement of fructose across the gut was not affected by loperamide which is therefore unlikely to act by reducing tissue permeability [25].
• The effect of loperamide and naloxone on mouth-to-caecum transit time was evaluated by the lactulose hydrogen breath test in four men and four women [26].
• METHODS: To test this hypothesis, a 16-mg dose of loperamide was administered to eight healthy male volunteers in the presence of either 600 mg quinidine, a known inhibitor of P-glycoprotein, or placebo [14].

Gene context of loperamide

• We investigated the modulation of the central nervous effects of loperamide resulting from ABCB1 genetic variants [27].
• Loperamide is a strong inhibitor of CES2, with a K(i) of 1.5 muM, but it only weakly inhibits CES1A1 (IC(50) = 0.44 mM) [28].
• Loperamide (10 micromol/l for 24 h) reversed the inhibition of insulin-stimulated 2-DG uptake by TNFalpha in a manner sensitive to blockade of opioid mu-receptors [29].
• OBJECTIVE: The purpose of the present study was to elucidate the cytochrome P450 (P450) isoform(s) involved in the metabolism of loperamide (LOP) to N-demethylated LOP (DLOP) in human liver microsomes [30].
• LVP increased ACTH levels after both loperamide (from 48 +/- 17.3 to a peak of 95 +/- 21 pmol/l) and placebo (from 231 +/- 59.5 to 365 +/- 86.6 pmol/l): the interaction between treatments and time was not significant [31].

Analytical, diagnostic and therapeutic context of loperamide

• Loperamide also had no effect during steady-state perfusion when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide [32].
• Management of radiation-induced diarrhea is similar but may not require hospitalization, and chronic low- to intermediate-grade symptoms can be managed with continued loperamide [33].
• We examined the effect of two drugs, codeine phosphate and loperamide, on upper intestinal transit and carbohydrate absorption, measured non-invasively by serial exhaled breath hydrogen monitoring, in patients with postvagotomy diarrhoea who had previously failed to gain relief from drug therapy [34].
• Each subject underwent tests during the administration of placebo, loperamide (12-16 mg po), naloxone (40 micrograms/kg/h by a three-hour intravenous infusion), and loperamide plus naloxone, carried out at intervals of one or two weeks [26].
• In study II, as in study I, unlike loperamide and placebo, codeine induced pupillary constriction [35].

References