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PubMed1986

Inhibitory actions of loperamide on absorptive processes in rat small intestine.

Mucosal loperamide caused a dose dependent reduction in the absorption of actively transported hexoses and amino acids, together with the associated rise in short circuit current. Na+ and fluid movement were also inhibited. Serosal application of the drug was without effect on these processes. The passive movement of fructose across the gut was not affected by loperamide which is therefore unlikely to act by reducing tissue permeability. In low Na+ conditions the inhibitory actions of loperamide on glycine absorption were reduced. Loperamide reduced basal Na+ transport although it did not affect the stimulation of Na+ absorption caused by mannose. Loperamide had no effect on the total ATPase activity nor on the Na+, K+-ATPase activity of mucosal homogenates. The effects of loperamide were not mimicked by morphine nor were they antagonised by naloxone and hence do not seem to involve an opiate receptor. It is concluded that loperamide exerts its inhibitory effects by an interaction with the Na+ sites of the nutrient carriers.

Animals↗
PubMed1996

Modification of nasal membrane potential difference with inhaled amiloride and loperamide in the cystic fibrosis (CF) mouse.

BACKGROUND: In the airway of subjects with cystic fibrosis (CF) the combination of defective cAMP mediated chloride secretion and enhanced sodium absorption leads to dehydration of mucosal mucus and is reflected in an increased trans-epithelial potential difference (PD). The airway secretions may be less viscid and easier to expectorate if sodium (and water) reabsorption is inhibited. METHODS: To evaluate the response to sodium blocking agents, changes in the nasal PD in 20 transgenic CF mice were compared with 14 control mice (MF1 strain) before and after administration of nebulised amiloride and loperamide (both in a concentration of 1 mmol/l). The duration of action for both drugs was also determined after a single inhaled dose of 1 mmol/l for two minutes. RESULTS: The median basal PD was -24 mV in controls and -28 mV in CF mice (p < 0.01). This fell in CF mice after amiloride and loperamide administration by 15 mV and 14 mV, respectively, compared with a decrease of 7 mV and 5.5 mV in controls (p < 0.01). There was no further change in PD when loperamide was given after amiloride. This suggests that loperamide and amiloride may act on sodium absorption via similar mechanisms. Loperamide had a longer duration of action after a single administration than amiloride. CONCLUSION: The administration of amiloride and loperamide reduces the transepithelial potential and inhibits sodium reabsorption in the CF mouse airway. Further studies are required to determine if the more prolonged action of loperamide could be of therapeutic use.

Amiloride↗
PubMed1993

Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial.

PURPOSE: Diarrhea is a prominent feature of fluorouracil (5FU) gastrointestinal toxicity, especially when 5FU is combined with leucovorin (LV) or interferon (IFN). No treatment for this condition has been well defined, although drugs, such as diphenoxylate or loperamide, generally are used. The efficacy of octreotide in the treatment of 5FU-induced diarrhea recently has been reported. We performed a randomized trial that compared octreotide with loperamide, the drug most commonly used for therapy for this disorder. PATIENTS AND METHODS: Forty-one patients with grade 2 (four to six stools per day) or grade 3 (seven to nine stools per day; National Cancer Institute toxicity criteria) diarrhea after chemotherapy with a 5FU-containing regimen for colorectal cancer in 28 cases, gastric cancer in six cases, pancreatic cancer in five cases, and breast cancer in two cases, were entered onto the study. Twenty-one patients received octreotide at a dosage of 0.1 mg subcutaneously twice per day for 3 days, and 20 patients received loperamide 4 mg orally initially and then 2 mg every 6 hours for 3 days. The two arms were comparable for age, sex, and primary tumor. Patients were evaluated for response each treatment day; all patients were assessable. RESULTS: Diarrhea resolved in 19 patients in the octreotide arm (one within the first day; four within the second day; and 14 within the third day) versus only three (all after the third day of therapy) in the loperamide arm (P < .005). Median frequency of stools in the 3 days of therapy was four, three, and zero in the octreotide arm and five, five, and five in the loperamide arm. No side effects were observed in both arms. Ten patients on the loperamide arm and only one on the octreotide arm required hospitalization for parenteral replenishment of fluids and electrolytes. CONCLUSION: Octreotide seems to be more effective than loperamide in control of diarrhea and elimination of the need for replenishment of fluids and electrolytes.

Adult↗
PubMed1978

[Pharmacological studies of loperamide, an anti-diarrheal agent. II. Effects on peristalsis of the small intestine and colon in guinea pigs (author's transl)].

Effects of loperamide on peristalsis in the guinea pig intestines were investigated in comparison with those of morphine and atropine. The following results were obtained. The ejection of intraluminal fluid produced by the peristaltic contraction of the isolated ileum was suppressed by loperamide at a concentration of 10(-8) or 2 X 10(-8) g/ml. Peristalsis in the intestinal loop of anesthetized guinea pigs was inhibited by i.v. administration of loperamide at a dose of 0.03 mg/kg. Morphine (0.03 mg/kg i.v.) and atropine (0.05 mg/kg i.v.) also inhibited the peristaltic contraction. The effect of loperamide continued longer than that of morphine. Peristalsis in the colonic loop of anesthetized guinea pigs was inhibited by i.v. administration of loperamide at a dose of 0.01 or 0.03 mg/kg. Morphine (0.1 mg/kg i.v.) and atropine (0.03 mg/kg i.v.) also inhibited the peristaltic contraction of the colonic loop. Loperamide (0.01 or 0.03 mg/kg i.v.) and morphine (0.1 mg/kg i.v.) caused a slight and temporary increase of resting level of intraluminal pressure with inhibition of peristalsis in the colonic loop. These results suggest that loperamide suppresses the peristaltic contraction caused by distension of the intestinal lumen.

Animals↗
PubMed2005

Loperamide inhibits tachykinin NK3-receptor-triggered serotonin release without affecting NK2-receptor-triggered serotonin release from guinea pig colonic mucosa.

The effect of loperamide on tachykinin NK(2)- and NK(3)-receptor-mediated 5-HT outflow from guinea pig colonic mucosa was investigated in vitro. The selective tachykinin NK(2)-receptor agonist [beta-Ala(8)]-neurokinin A(4-10) (betaAla-NKA) or the selective NK(3)-receptor agonist senktide elicited an increase in 5-HT outflow from whole colonic strips, but not from mucosa-free muscle layer preparations. The enhancing effect of betaAla-NKA and senktide was prevented by the selective NK(2)-receptor antagonist GR94800 or the selective NK(3)-receptor antagonist SB222200. Loperamide concentration-dependently suppressed the senktide-evoked 5-HT outflow, but failed to affect the betaAla-NKA-evoked 5-HT outflow. The kappa-opioid receptor antagonist nor-binaltorphimine or the delta-opioid receptor antagonist naltrindole displaced the concentration-response curve for the suppressant action of loperamide to the right without significant depression of the maximum. However, the mu-opioid receptor antagonist CTOP did not affect the suppressant effect of loperamide. We concluded that the NK(3) receptor-triggered 5-HT release from colonic mucosa is suppressed by loperamide-sensitive mechanisms, whereas the NK(2)-receptor-triggered 5-HT release is loperamide-insensitive. Our data also suggest that the suppressant effect of loperamide is probably mediated by the activation of kappa- and delta-opioid receptors located on intrinsic neurons.

Animals↗
PubMed1991

Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial.

OBJECTIVE: To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: United States Army hospital in Egypt. PARTICIPANTS: United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded. INTERVENTIONS: All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo. MEASUREMENTS: Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common. MAIN RESULTS: After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19). CONCLUSIONS: In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe.

Ciprofloxacin↗
PubMed2000

Inhibition of thromboxane A(2)-induced Cl(-) secretion by antidiarrhea drug loperamide in isolated rat colon.

The antitumor drug irinotecan clinically causes severe diarrhea as a side effect. Thromboxane A(2) (TXA(2)), released by irinotecan, has been shown to be a novel physiological stimulant of Cl(-) secretion in the rat colon. Herein, we examined the effect of loperamide, an antidiarrhea drug, on Cl(-) secretion induced by irinotecan; 9, 11-epithio-11,12-methano-thromboxane A(2) (STA(2)), a stable TXA(2) analog; and prostaglandin E(2) (PGE(2)) by using isolated mucosae of the rat colon. In the presence of atropine, loperamide in a concentration-dependent manner inhibited the Cl(-) secretion induced by irinotecan, STA(2), and PGE(2). However, the drug inhibited more effectively the irinotecan- and STA(2)-induced secretion (IC(50) = 0. 7 and 1.2 microM, respectively) than the PGE(2)-induced secretion (IC(50) = 23 microM). Naloxone, an opiate antagonist, did not affect the antisecretory action of loperamide. Similar to the case for loperamide, W-7, a specific calmodulin antagonist, inhibited more effectively the STA(2)-induced Cl(-) secretion (IC(50) = 5 microM) than the PGE(2)-induced secretion (IC(50) = 36 microM). W-5, a low-affinity calmodulin antagonist (a dechlorinated control analog of W-7), also inhibited the STA(2)-induced secretion, but this effect was much less than that of W-7. STA(2)-induced increase in the intracellular free Ca(2+) concentration of single colonic crypt cells was not affected by loperamide. We suggest that loperamide efficiently inhibits the TXA(2)-induced secretion by blocking the calmodulin system in the colonic epithelium. The present results may explain why coadministration of loperamide with irinotecan is clinically efficient for avoiding the irinotecan-induced side effect of diarrhea.

Animals↗
PubMed2005

Acute analgesic effect of loperamide as compared to morphine after intrathecal administration in rat.

Loperamide, a mu opioid receptor agonist, which is commonly used as an antidiarrhoeal agent has been reported to possess analgesic activity after intrathecal administration. However, the exact analgesic profile, i.e., onset, duration and intensity of analgesia in relation to morphine is not fully known. In the present study, the acute analgesic effect of loperamide (5 microg) was compared with that of morphine (5 microg) and morphine + loperamide (5 microg of each) using the tail flick method after intrathecal administration. Naloxone (5 mg/kg) reversibility of the analgesic effect was also studied. The analgesic response of loperamide was significantly higher than morphine. Even after 22 hr, maximum possible effect was greater than 49%. Naloxone partially antagonized the analgesic effect of loperamide. This suggested that loperamide may be acting through blockade of Ca2+ channels besides activating mu opioid receptors. Loperamide may prove to be a better substitute for morphine as spinal analgesic.

Analgesics↗
PubMed1987

Inhibition of brush-border membrane Na+-H+ exchanger by loperamide.

Loperamide, an opiate agonist, inhibited the Na+-H+ exchanger in brush-border membrane vesicles isolated from term human placenta, rabbit renal cortex and rabbit small intestine in a dose dependent manner. Because the placental Na+-H+ exchanger was the most sensitive to inhibition by loperamide (IC50 = 60 microM), characterization of the inhibition was done with the placental Na+-H+ exchanger. The inhibition of the placental Na+-H+ exchanger by loperamide was instantaneous and freely reversible. Kinetic analyses demonstrated that the inhibition was of a mixed type. Loperamide (70 microM) reduced the maximal velocity (Vmax) from 46.4 +/- 1.2 to 34.5 +/- 1.1 nmol/mg of protein/15 s and increased the apparent affinity constant (Kt) for Na+ from 12.3 +/- 1.0 to 16.5 +/- 1.5 mM. Loperamide interacted with the exchanger protein at more than one site. The effects of loperamide were not antagonized by naloxone, suggesting the noninvolvement of opiate receptors in this process. These results differentiate loperamide from other Na+-H+ exchanger inhibitors such as amiloride, cimetidine and clonidine, which interact with the exchanger at a single site in a strictly competitive manner.

Amiloride↗
PubMed1987

Effects of loperamide hydrochloride on experimental diarrhea and gastrointestinal myoelectrical activity in calves.

The antidiarrheal action of loperamide hydrochloride was tested against diarrhea experimentally induced in calves by intraduodenal infusion of castor oil or hypertonic solution of mannitol. The motility of 4 levels of the digestive tract (abomasum, jejunum, and proximal and spiral loops of the colon) was concomitantly recorded, using an electromyographic technique. Loperamide hydrochloride given per os at 0.4 mg/kg or intraduodenally or subcutaneously at 0.1 mg/kg 1 hour before mannitol or castor oil was given delayed diarrhea. Loperamide hydrochloride given alone orally at a dosage of 0.4 mg/kg did not modify the motility pattern of the digestive tract. Intraduodenally administered loperamide hydrochloride (0.1 mg/kg) increased the frequency of the cyclic activity of the jejunum, whereas subcutaneously administered loperamide hydrochloride at the same dose selectively inhibited the motility of the jejunum. Intraduodenal infusion of mannitol was followed by a disruption of the cyclic activity of the jejunum, and this effect was not antagonized by loperamide hydrochloride, whatever the route of administration. Castor oil infusion was not accompanied with changes in gastrointestinal motility. These results indicate that loperamide hydrochloride is active against an experimentally induced diarrhea in calves and that this action is not mediated through an effect on the digestive motility, at least monitored by this electromyographic technique.

Abomasum↗
PubMed1984

Loperamide: blockade of calcium channels as a mechanism for antidiarrheal effects.

The antidiarrheal opiates loperamide, fluperamide, diphenoxylate and fetoxylate inhibited binding of [3H]nitrendipine to membranes from guinea-pig cerebral cortex with Ki values of 0.5 to 10 microM. Loperamide and fluperamide reversed the tiapamil elicited lowering of [3H]nitrendipine binding with IC50 values of 0.2 to 0.5 microM, indicating a verapamil-like action of these drugs. An oral dose of 1 mg/kg of loperamide reduced gastrointestinal motility and gave concentrations of 0.45 +/- 0.19, 0.38 +/- 0.22 and 0.49 +/- 0.25 microM in the duodenum, jejunum and ileum, respectively. The apparent Ki for loperamide in preventing calcium-induced contractions of guinea-pig ileum depolarized with 80 mM potassium was 0.10 microM. We propose that calcium channel antagonism is responsible at least in part for the antidiarrheal actions of loperamide and related agents. Evidence includes the calcium antagonist actions of loperamide at antidiarrheal doses, the constipating effects of certain calcium antagonists and the failure of opiate antagonists to prevent some intestinal effects of loperamide.

Animals↗
PubMed1976

Loperamide in chronic diarrhea and after ileostomy: a placebo-controlled double-blind cross-over study.

Fifteen patients (20 to 66 years) with long-standing chronic diarrhea of varying etiology were selected for an open trial of loperamide 2 mg capsules. The optimal daily dose for substantial reduction of the diarrhea ranged from two to seven capsules. Eleven patients showed a significant improvement in stool consistency and stool frequency, and a decrease of abdominal cramps. Loperamide appeared to be ineffective in two patients with cholerrheic diarrhea, and in one patient with laxative-induced diarrhea, and in one patient with diarrhea of unknown etiology. The eleven successfully treated patients then entered a double-blind placebo-controlled trial for ten days or until relapse, the daily dose being identical to the optimal one previously determined in the open phase. The investigator was able to guess the code correctly in ten out of eleven cases. Twenty ileostomy patients (ages 25 to 73 years) volunteered for the evaluation of the inhibitory activity on small intestinal peristalsis by loperamide in a double-blind placebo-controlled cross-over study. Mean daily ileostomy output decreased by 22% in the loperamide period, as compared with the drug-free study phase (P less than 0.001). Of the 20 patients, 16 were able to guess their code correctly, whereas four were uncertain, although their fecal weights were lower with loperamide. Many patients noticed an increased urinary production and experienced an improvement in their ileostomy care during loperamide treatment. Because of its effectiveness, its low side-effect liability and its lack of toxicity, loperamide is considered a promising drug in the symptomatic treatment of chronic diarrhea, and as a reliable agent in the treatment of ileostomy patients.

Adult↗
PubMed1997

Single Dose Ofloxacin plus Loperamide Compared with Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea.

Background: Although the use of the antimicrobial, trimethoprim-sulfamethoxazole, in combination with the antisecretory and antimotility agent, loperamide, has been shown to be efficacious in the treatment of traveler's diarrhea, the use of fluoroquinolone antimicrobials in combination with loperamide has less support in the literature. The present study was designed to compare the efficacy of ofloxacin versus ofloxacin plus loperamide in the treatment of acute traveler's diarrhea. Method: This prospective, randomized, evaluator-blinded treatment trial was conducted in Guadalajara, Mexico, during the summers of 1992-1994. Adults newly arrived in Mexico from the United States who developed acute diarrhea of less than 2 weeks' duration were randomized to receive orally either: A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose stool, not to exceed 16 mg per day, for 3 days. The duration of illness was the number of hours elapsed from the beginning of therapy to the passage of the last unformed stool. Results: Ofloxacin and loperamide were well tolerated. Combination therapy with single dose ofloxacin plus loperamide was significantly more efficacious in reducing the duration of diarrhea than single dose ofloxacin or ofloxacin given for 3 days (p <.00001). Furthermore, combination therapy was more efficacious when enterotoxigenic Escherichia coli (ETEC) was the pathogen (p <.01) or when no pathogen was isolated (p <.001). Sixty-three percent of subjects passed no further unformed stools after the initial doses of combination therapy, and 91% were well by the end of the first 24 hours. Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone.

Journal Article↗
PubMed1995

Randomized trial of loperamide versus dose escalation of octreotide acetate for chemotherapy-induced diarrhea in bone marrow transplant and leukemia patients.

This study compares maximal daily doses of loperamide to escalating doses of continuous intravenous (CI) octreotide acetate in bone marrow transplant (BMT) and leukemia patients. Following chemotherapy, BMT and leukemia patients who developed > or = 600 ml of stool volume in a 24-hr period were randomized to receive loperamide 4 mg po q6h or octreotide 150 micrograms mixed in hyperalimentation solution or normal saline and administered CI. Patients were assessed at 48 hr intervals for decrease in stool volume from baseline. Complete response (CR) was defined as > or = 50% from baseline stool volume (BSV). Patients receiving octreotide who did not achieve a CR at 48 hr were dose escalated by doubling the dose to a maximum of 2,400 micrograms with evaluations at 48 hr intervals. Patients receiving loperamide who did not achieve a CR at 48 hr had treatment discontinued. A total of 36 patients were enrolled in the study. Of these, all were evaluable for intention to treat, and 31 were evaluable for initial response. Based on intent to treat at the initial 48 hr, patients receiving loperamide had a higher complete response rate (86% vs. 45%, P = 0.033) than did those who received octreotide. By treatment analysis (patients who actually received the drug), patients receiving loperamide had a higher complete response rate (92% vs. 56%, P = 0.0448) than did those who received octreotide at the 150 micrograms dosage level. Additional octreotide patients eventually achieved a CR at a higher dosage level (78%). Loperamide at maximal doses of 4 mg po q6h is more effective than octreotide 150 micrograms CI in treating diarrhea following chemotherapy in BMT and leukemia patients. Higher doses of octreotide may be required in a significant number of patients not responding to lower doses.

Adult↗
PubMed1979

Human pharmacokinetics and comparative bioavailability of loperamide hydrochloride.

A pharmacokinetic study of the antidiarrheal agent loperamide hydrochloride (Imodium) was conducted in six male subjects. The study utilized a random crossover design and employed a 2-mg capsule and a 0.2-mg/ml syrup formulation. Each treatment consisted of a single oral dose of 8 mg loperamide HCl followed by a two-week interval before the next treatment. Serum and urine samples obtained at various times after drug administration were assayed for loperamide using a radioimmunoassay specific for the drug. The mean biologic half-life, calculated from the elimination phase of the log serum concentration-versus-time data, was 10.8 +/- 0.6 hours for the overall study, 10.2 +/- 0.6 hours for the syrup formulation, and 11.2 +/- 0.8 hours for the capsules. The loperamide from the syrup was absorbed more rapidly than from the capsule formulation, with the peak serum levels observed at a mean time of 2.4 +/- 0.7 hours for the syrup and 5.2 +/- 0.3 hours for the capsule formulation. The relative areas under the serum loperamide concentration-versus-time curves suggested that the two formulations have comparable physiologic availability. The maximum observed serum concentrations were also similar, indicating the safety of the syrup formulation. Excretion of approximately 1 per cent of the dose in the urine as unchanged loperamide after seven days was observed independent of the particular dosage form that was administered.

Adult↗
PubMed1993

Difenoxin and loperamide: studies on possible mechanisms of intestinal antisecretory action.

Experiments have been performed to determine whether the antisecretory (antidiarrhoeal) actions of difenoxin and loperamide are mediated by enteric neurones. An iso-osmotic perfusion solution was circulated around the lumen of the jejunum of anaesthetised rats. Vasoactive intestinal peptide was infused intra-arterially to induce net fluid secretion which was inhibited by difenoxin (ED50, 0.23 mg/kg) and loperamide (ED50, 0.5 mg/kg). However, neither were able to restore the fluid transport rate to the control level of absorption. The antisecretory effects of difenoxin (0.77 mg/kg) and loperamide (0.6 mg/kg) were blocked by the opiate receptor antagonist naloxone (2 mg/kg). Their effects were also abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 200 mg/kg; with desmethylimipramine given beforehand to protect noradrenergic nerves and enhance 5-HT depletion). The effect of difenoxin was blocked with methiothepin (1 mg/kg) and methysergide (30 micrograms/kg) but not ketanserin (30 micrograms/kg), ritanserin (30 mg/kg), ondansetron (10 micrograms/kg) or ICS 205-930 (3 mg/kg). None of the above 5-HT receptor antagonists modified the antisecretory effect of loperamide. The antisecretory effect of difenoxin but not loperamide was prevented by phentolamine (2 mg/kg) and by pretreatment with 6-hydroxy-dopamine (150 mg/kg total). It is concluded that both difenoxin and loperamide inhibit net fluid secretion by indirect mechanisms. It is proposed that the initial action is on enteric mu-opiate receptors and that this results in the release of 5-HT. In the case of difenoxin, the 5-HT may act on 5-HT1-like receptors to release noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Oral naloxone antagonizes loperamide-induced delay of orocecal transit.

Orocecal transit time was determined by the lactulose hydrogen breath test in nine healthy volunteers after administration of placebo, loperamide (16 mg per os), and loperamide (16 mg per os) followed by oral naloxone at doses of 16 and 32 mg. The four tests were performed in double-blind conditions and in random sequences. Transit time (mean, SD) after loperamide (128.8 min, 32.9) was significantly increased (P less than 0.05) compared with placebo (85.5 min, 35.7), loperamide followed by naloxone 16 mg (88.8 min, 46.2), and loperamide followed by naloxone 32 mg (84.4 min, 40.6). These results show that the peripheral opioid agonist loperamide delays orocecal transit in healthy subjects and that naloxone per os at adequate doses antagonizes this effect.

Administration, Oral↗
PubMed1990

Naloxone-insensitive transport effects of loperamide in guinea-pig gallbladder epithelium.

The effects of the antidiarrheal drug, loperamide, on HCO3 and Na transport across guinea-pig gallbladder epithelium were investigated using Ussing-chamber methods. Under basal conditions, mucosal loperamide (10(-4) mol/l) moderately lowered both the absorptive (JHCO3ms) and the secretory HCO3 flux (JHCO3sm) (pH-stat method), most likely by changing paracellular HCO3 flow. Exposure to serosal prostaglandin E1 (10(-6) mol/l) abolished Na absorption and turned HCO3 secretion electrogenic. The associated short-circuit current (Isc) was inhibited by loperamide in a concentration-dependent manner; mucosal addition (threshold at 3 x 10(-6) mol/l) of the drug was more effective. Inhibition of Isc was related to a decrease in JHCO3sm, but exceeded the drop in JHCO3net. The effects on JHCO3sm and Isc were mimicked by [Met5]enkephalin. Naloxone (10(-6) mol/l) was unable to influence the effects of loperamide and [Met5]enkephalin on Isc. There were no pro-absorptive effects of loperamide on unidirectional Na fluxes. We conclude that antisecretory properties of loperamide are solely due to inhibition of electrogenic HCO3 secretion, an effect unrelated to opiate receptor binding.

Alprostadil↗