Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new imodium research articles will be listed here shortly after becoming available to us.
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Medical research on imodium
The role of loperamide in gastrointestinal disorders.
Rev Gastroenterol Disord. 2008; 8(1): 15-20
Hanauer SB
Loperamide is an effective therapy for a variety of diarrheal syndromes, including acute, nonspecific (infectious) diarrhea; traveler's diarrhea; and chemotherapy-related and protease inhibitor?associated diarrhea. Loperamide is effective for the "gut-directed" symptom of diarrhea in patients with painless diarrhea or diarrhea-predominant irritable bowel syndrome. Loperamide and diphenoxylate are commonly used to treat diarrhea in numerous settings of inflammatory bowel disease. Loperamide has also been observed to increase anal sphincter tone, which may lead to improvement of fecal continence in patients with and without diarrhea. Loperamide is generally well tolerated at recommended nonprescription doses, with the most common side effects related to the impact on bowel motility (abdominal pain, distention, bloating, nausea, vomiting, and constipation).
Br J Pharmacol. 2008 Jul; 154(5): 1001-8
Capasso R, Borrelli F, Aviello G, Romano B, Scalisi C, Capasso F, Izzo AA
Background and purpose:Cannabidiol is a Cannabis-derived non-psychotropic compound that exerts a plethora of pharmacological actions, including anti-inflammatory, neuroprotective and antitumour effects, with potential therapeutic interest. However, the actions of cannabidiol in the digestive tract are largely unexplored. In the present study, we investigated the effect of cannabidiol on intestinal motility in normal (control) mice and in mice with intestinal inflammation.Experimental approach:Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with ACh.Key results:In vivo, cannabidiol did not affect motility in control mice, but normalized croton oil-induced hypermotility. The inhibitory effect of cannabidiol was counteracted by the cannabinoid CB(1) receptor antagonist rimonabant, but not by the cannabinoid CB(2) receptor antagonist SR144528 (N-[-1S-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide), by the opioid receptor antagonist naloxone or by the alpha(2)-adrenergic antagonist yohimbine. Cannabidiol did not reduce motility in animals treated with the fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine, whereas loperamide was still effective. In vitro, cannabidiol inhibited ACh-induced contractions in the isolated ileum from both control and croton oil-treated mice.Conclusions and implications:Cannabidiol selectively reduces croton oil-induced hypermotility in mice in vivo and this effect involves cannabinoid CB(1) receptors and FAAH. In view of its low toxicity in humans, cannabidiol may represent a good candidate to normalize motility in patients with inflammatory bowel disease.British Journal of Pharmacology (2008) 154, 1001-1008; doi:10.1038/bjp.2008.177; published online 12 May 2008.
Mol Pharmacol. 2008 May 7;
Borner C, Kraus J, Bedini A, Schraven B, Hollt V
Opiates function as immunomodulators, partly by effects on T cells. Opioids act via micro-, delta- and kappa-opioid receptors, among which the micro-type is of particular interest, since morphine-like opioids preferentially bind to it. Here we report that micro-opioid receptor mRNA was induced after CD3/28-mediated activation of primary human T lymphocytes and Jurkat T cells, which both do not express the gene constitutively. Moreover, a reporter gene construct containing 2624 bp of the micro-opioid receptor promoter was trans-activated by CD3/28-stimulation. Transcriptional induction of the micro-opioid receptor gene was mediated by AP-1, NF-kappaB and NFAT. NFAT was found to bind to three sequences of the micro-opioid receptor promoter, located at nucleotides -1064, -785 and -486. Although the -486 element is in close proximity to a putative AP-1 site, there was no evidence for a combined AP-1/NFAT site. Furthermore, we demonstrated that the induction of interleukin-2 mRNA and protein in activated T cells was inhibited by morphine in cells, in which micro-opioid receptors had been induced by CD3/28 mAbs and that this effect was blocked by the micro-opioid receptor-specific antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). CD3/28 mAbs-induced interleukin-2 transcription was also inhibited by the opioids fentanyl and loperamide. This indicates that the induced micro-opioid receptor mRNA is translated into functional receptor protein. Furthermore, a micro-opioid receptor-enhanced green fluorescent protein-fusion protein was localized in membranes of Jurkat cells and internalized in response to [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-Enkephalin (DAMGO), but not morphine. In conclusion, these data emphazise the role of opioids in the modulation of T lymphocyte signaling.
Z Gastroenterol. 2008 May; 46(5): 441-8
Zimmerer T, Böcker U, Wenz F, Singer MV
BACKGROUND: Radiation enteritis is a severe problem in patients receiving irradiation of the abdomen or pelvis in the course of cancer treatment. Nevertheless, there is a lack of standardised strategies for medical prevention and therapy. MATERIALS AND METHODS: A PubMed based literature search was performed to address the available data on the prevention of and therapy for acute and chronic radiation enteritis. RESULTS: Four double-blind and placebo-controlled studies used 5-aminosalycilates in the prevention of acute radiation enteritis. Only for sulphasalzine 2 g/d was a positive effect proven. Prophylactic administration of probiotics reduced the incidence of acute radiation enteritis in a large placebo-controlled trial. If acute radiation enteritis was present octreotide ameliorated radiation-induced diarrhoea in a randomised study. Two investigations, only one of them randomised, described the effectiveness of loperamide in the treatment of acute radiation enteritis. If diarrhoea was also the main symptom of chronic radiation enteritis, loperamide reduced stool frequency in a double-blind and placebo-controlled study. A retrospective analysis of severe cases of chronic radiation enteritis with obstruction and fistula indicated that parenteral nutrition at home was more effective than surgery. CONCLUSION: Reduction of radiation dose and field size are still the most important factors in the prevention of acute and chronic radiation enteritis. Valid data particularly on the treatment of chronic radiation enteritis are lacking. A better understanding of the pathopysiology especially in chronic radiation enteritis might offer new therapeutic perspectives. Inhibition of TGF-beta, for example, might be a new promising therapy approach.
Eur J Pharmacol. 2008 Jun 10; 587(1-3): 281-4
Hirata T, Keto Y, Nakata M, Takeuchi A, Funatsu T, Akuzawa S, Sasamata M, Miyata K
The effects of corticotropin releasing factor (CRF) and serotonin (5-HT)(3) receptor antagonists on intestinal water transport are not well understood. Hence, we established a CRF-induced abnormal water transport model in rat colon, and evaluated the effects of 5-HT(3) receptor antagonists including ramosetron, alosetron, and cilansetron, and the antidiarrheal agent loperamide, in this model. In addition, the effects of 5-HT(3) receptor antagonists and loperamide on abnormal defecation induced by CRF in rats were examined. Colonic water transport was measured in colonic loops in conscious rats. Centrally administered CRF (3-30 mug/kg) markedly decreased colonic fluid loss, whereas oral administration of ramosetron (3, 30 mug/kg), alosetron (300 mug/kg), cilansetron (300 mug/kg), or loperamide (3 mg/kg) significantly inhibited it. Ramosetron (1-10 mug/kg), alosetron (10-100 mug/kg), cilansetron (10-100 mug/kg), or loperamide (0.3-3 mg/kg) also showed dose-dependent inhibition of CRF-induced defecation in rats. These results suggest that 5-HT(3) receptors are involved in both abnormal colonic water transport and defecation induced by CRF, and that the inhibitory effects of 5-HT(3) receptor antagonists on CRF-induced abnormal defecation partly result from their ameliorating action on colonic water transport.
Drug Metab Dispos. 2008 Apr 30;
Aidasani D, Zaya MJ, Malpas PB, Locuson CW
Little information regarding the metabolic pathways of pharmaceutical agents administered to dogs, or the inhibition of those metabolic pathways, is available. Without this information, it is difficult to assess how combinations of drugs, whether new or old, approved or non-approved, may increase the risk for metabolic drug-drug interactions in dogs. Since mammalian xenobiotic metabolism pathways often involve the hepatic cytochrome P450 monooxgenases, canine liver microsome P450 inhibition screens were tested to evaluate the potential metabolic drug interaction risk of commonly used veterinary medicines. A probe substrate cocktail was developed for four of the five major hepatic canine P450s and used to evaluate their inhibition by 45 canine therapeutics in a single point IC50 screen. Moderate inhibitors (> 25 %) were further characterized with an automated nine point IC50 assay which identified ketoconazole, clomipramine, and loperamide as sub-micromolar CYP2D15 inhibitors. Additional inhibitors belonged to the anti-emetic, anti-mitotic, and anxiolytic therapeutic classes. According to the marker activities, the relative frequency of P450 inhibition by isoform followed the sequence CYP2D15 > CYP2B11 > CYP2C21/41 > CYP3A12/26 > CYP1A1/2. The findings presented suggest there is some overlap in canine and human P450 inhibition specificity. However, occasional differences may give human drugs used off-label in dogs unexpected P450 inhibition profiles, and therefore, unexpected drug-drug interaction risk.
[Time and again digestion problems. What really helps in irritable bowel syndrome?]
MMW Fortschr Med. 2005 Feb 24; 147(8): 16
Loperamide use for acute infectious diarrhea in children: safe and sound?
Gastroenterology. 2008 Apr; 134(4): 1260-2
Pulling M, Surawicz CM
Maternal use of loperamide in early pregnancy and delivery outcome.
Acta Paediatr. 2008 May; 97(5): 541-5
Källén B, Nilsson E, Otterblad Olausson P
AIM: To study delivery outcome including presence of infant congenital malformations after maternal use of loperamide in early pregnancy. METHODS: Using the Swedish Medical Birth Register, women reporting the use of loperamide in early pregnancy were compared with other women for the period July 1, 1995-2004. Odds ratios (OR) or risk ratios (RR) were estimated after adjustment for some variables, which were associated with the use of loperamide (year of delivery, maternal age, parity, smoking, number of previous miscarriages). RESULTS: Characteristics of women using loperamide in early pregnancy were identified. An analysis of concomitant drug use indicated that only few of the women had inflammatory bowel disease. The risk of any congenital malformation was increased (OR = 1.43, 95% CI 1.04-1.96), based on 43 cases, but no major contributing type could be identified. The risk of hypospadias was significantly increased (RR = 3.2, 95% CI 1.3-6.6), based on seven cases. A statistically significant increase was seen also for placenta previa, large for gestational age and caesarean section. CONCLUSION: Maternal use of loperamide in early pregnancy may be associated with a moderate risk increase for a malformation in the infant. The finding should be evaluated from other large studies.
Cell Mol Neurobiol. 2008 Mar 22;
Curto-Reyes V, Juárez L, García-Pérez E, Fresno MF, Hidalgo A, Menéndez L, Baamonde A
The stimulation of peripheral opioid receptors counteracts thermal hyperalgesia produced by the intratibial inoculation of NCTC 2472 cells in mice, through the activation of the nitric oxide/cGMP/ATP-sensitive K(+)-channels (NO/cGMP/K(+) (ATP)) cascade (Menéndez et al. 2007, Neuropharmacology 53:71-80). We aimed to elucidate whether this peripheral opioid antihyperalgesic effect is exclusive to this model or might also occur in other types of bone neoplastic processes. In C57BL/6 mice intratibially inoculated with B16-F10 melanoma cells, the progressive tumoral damage was accompanied by the establishment of thermal hyperalgesia (unilateral hot plate test) and mechanical allodynia (von Frey test). Intraplantar administration of loperamide (15 mug, 30 min before) inhibited thermal hyperalgesia, but did not modify the intense mechanical allodynia. The fact that the coadministration of naloxone-methiodide (5 mug) completely suppressed the thermal antihyperalgesic effect induced by loperamide indicates its production through the stimulation of peripheral opioid receptors. Furthermore, its prevention by the coadministration of the non-selective inhibitor of the NO synthase, N(G)-monomethyl-L: -arginine (L-NMMA, 10 mug), the selective inhibitor of neural NOS, N-omega-propyl-L-arginine (1-10 mug), or the K(+) (ATP) channel blocker, glibenclamide (10 mug) demonstrated the involvement of the NO/cGMP/K(+) (ATP) pathway in the antihyperalgesic effect induced by loperamide. Overall, the present results show that the intratibial inoculation of B16-F10 cells to C57BL/6 mice evokes thermal hyperalgesia and mechanical allodynia and that, as occurred in the osteosarcoma model, the stimulation of peripheral opioid receptors is not effective in modifying neoplastic allodynia but completely inhibits thermal hyperalgesia through the activation of the NO/cGMP/K(+) (ATP) cascade.