- |||||||||| loperamide / Generic mfg.
Trial completion date: 4FMFES-PET Imaging of Endometrial and Ovarian Cancers (clinicaltrials.gov) - Jul 19, 2022
P1/2, N=72, Recruiting,
The developed approach is considered the first TLC method using smartphones for the determination of some gastrointestinal tract drugs in their pure form and in pharmaceutical formulations. Trial completion date: Aug 2022 --> Aug 2023
- |||||||||| imipramine / Generic mfg., loperamide / Generic mfg.
Journal: Extraction and Fractionation of Prokinetic Phytochemicals from Chrozophora tinctoria and Their Bioactivities. (Pubmed Central) - Jul 17, 2022
Some of them are compounds with known therapeutic activity, such as toluene; imipramine; undecane; 14-methyl-pentadecanoic acid methyl ester; and hexadecanoic acid...Both the samples of Chrozophora tinctoria revealed significant (p ≤ 0.01) laxative activity against metronidazole (7 mg/kg) and loperamide hydrochloride (4 mg/kg)-induced constipation...The present study scientifically validates the folk use of Chrozophora tinctoria in the management of gastrointestinal diseases such as constipation. Further work is needed to isolate the phytochemicals that act as diarrheal agents in Chrozophora tinctoria.
- |||||||||| ZSTK474 / Zenyaku Kogyo
Automated prediction of drug response in HCC cell lines with deep learning-based bioactivity modeling and experimental validation (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_250;
Results and Discussions Among a large group of predicted inhibitors, 4 compounds, 2 investigational drugs (Loperamide N-oxide and Eprinomectin), which were not studied on HCC before, and 2 PI3K/mTOR pathway inhibitors (Rapamycin and ZSTK474), which were previously studied on HCC cell lines, were selected for in vitro validation studies...Conclusion Our prediction model successfully predicts specific small molecule drugs for HCC cell lines. With additional in vitro validation experimentation, we hope to identify new inhibitors that have the potential to be repurposed against HCC.
- |||||||||| loperamide / Generic mfg.
Journal: Loperamide-induced ventricular tachycardia storm. (Pubmed Central) - Jun 25, 2022
This complicated the diagnostic process as a thorough history could not be obtained on arrival to the tertiary centre, which meant the loperamide misuse only came to light multiple days into admission, after the patient was extubated. The final diagnosis of loperamide-induced secondary long-QT syndrome was made and the patient made a full recovery.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: Antidiarrheal Effect of 80% Methanol Extract and Fractions of the Leaves of Ocimum lamiifolium in Swiss Albino Mice. (Pubmed Central) - Jun 8, 2022
Group I received 10 mL/kg of the dissolving vehicle, Group II received either loperamide or atropine, and Groups III-V received extract doses of 100, 200, and 400 mg/kg, respectively...Similarly, both the crude extract and distilled water fraction at 400 mg/kg as well as n-butanol and n-hexane fractions at 200 and 400 mg/kg showed meaningful differences on peristaltic index as compared to the negative control. The results revealed that the leaf extract of O. lamiifolium has an antidiarrheal activity, which supports the traditional medical practice.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: Loperamide-induced Constipation activates Inflammatory Signaling Pathways in the Transverse Colon of SD rats via Complement C3 and its receptors. (Pubmed Central) - May 29, 2022
Pterostilbene ameliorated the intestinal motility disorder induced by LOP, this effect might be achieved by inhibiting oxidative stress-induced apoptosis of ICCs through the PI3K/AKT/Nrf2 signaling pathway. These results indicate that Lop-induced constipation is tightly linked to the downregulation of C3aR and C3bR expressions, and upregulation of the C3 and C3Rs downstream signaling pathway, including PI3K/AKT, RhoA/MLC, and MAP kinase pathways as well as inflammatory cytokine expressions in the mid colon of SD rats.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: Evaluation of the effect of prebiotic sesame candies on loperamide-induced constipation in mice. (Pubmed Central) - May 26, 2022
The mechanism of PSC improving constipation might be that PSC improved the imbalance of gastrointestinal neurotransmitters and increased the content of short-chain fatty acids in feces. In conclusion, PSC dietotherapy could effectively alleviate the symptoms and lay a theoretical foundation for the development of an anti-constipation diet.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: Evaluation of Antidiarrheal Activity of 80% Methanol Extract and Solvent Fractions of the Leaves of Withania somnifera (L.) Dunal in Swiss Albino Mice. (Pubmed Central) - May 20, 2022
Mice were randomly divided into five groups (six mice per group): negative control, which received 2% Tween 80 in distilled water; positive control, which received 3 mg/kg loperamide; and three test groups (III, IV, and V), which were treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg of crude extract and solvent fractions, respectively...All tested doses of the crude extract and 200 mg/kg and 400 mg/kg of the aqueous and n-butanol fractions significantly reduced the motility of charcoal meal. This study demonstrated that the crude extract and solvent fractions of the Withania somnifera leaves have antidiarrheal activity and supported the folklore use of the plant.
- |||||||||| Recentin (cediranib) / AstraZeneca
Trial completion date, Trial primary completion date, Monotherapy, Metastases: Sunitinib or Cediranib for Alveolar Soft Part Sarcoma (clinicaltrials.gov) - May 20, 2022
P2, N=34, Active, not recruiting,
This study demonstrated that the crude extract and solvent fractions of the Withania somnifera leaves have antidiarrheal activity and supported the folklore use of the plant. Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023
- |||||||||| Miostat (carbachol) / Novartis
Journal: Dual Inhibition of Phosphodiesterase and Ca Channels Explains the Medicinal Use of Balanites aegyptiaca (L.) in Hyperactive Gut Disorders. (Pubmed Central) - May 15, 2022
The inhibitory effects of B. aegyptiaca on PDE were further confirmed when the pre-incubated extract shifted the isoprenaline-mediated relaxation curves (CRCs) towards the left, similar to papaverine, whereas the CCB-like effect was confirmed when the pre-incubated tissues with B. aegyptiaca caused deflection in the Ca CRCs towards the right, constructed in Ca free medium with suppression of the maximum response. Thus, this study provides detailed, mechanistic support for the medicinal use of B. aegyptiaca in the treatment of hyperactive gut disorders.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: Bifidobacterium longum relieves constipation by regulating the intestinal barrier of mice. (Pubmed Central) - May 12, 2022
Meanwhile, it inhibited inflammation and prevented loperamide-induced intestinal barrier damage in constipated mice by upregulating occludin and downregulating IL-1β and TNF-α. In summary, B. longum relieved constipation by regulating the intestinal barrier in constipated mice.
- |||||||||| remdesivir / Generic mfg.
Drug-drug interactions between antiretrovirals and remdesivir () - May 12, 2022 - Abstract #AIDS2022AIDS_775;
Other treatments for COVID-19 studied here did not demonstrate significant DDIs with ARVs. As new COVID-19 therapeutics emerge, and given the prevalence of HIV worldwide, DDIs with ARVs must continue to be assessed.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: Lactobacillus plantarum PS128 Promotes Intestinal Motility, Mucin Production, and Serotonin Signaling in Mice. (Pubmed Central) - May 12, 2022
To explore its mechanism of action in the gut, this study aimed to analyze the effects of L. plantarum PS128 ingestion on naïve and loperamide (Lop)-induced constipation mice...Furthermore, immunohistochemistry revealed that L. plantarum PS128 significantly increased the number of serotonin-containing intestinal cells in mice. Taken together, our results suggest that L. plantarum PS128 could promote intestinal motility, mucin production, and serotonin signal transduction, leading to a laxative effect in mice.
- |||||||||| loperamide / Generic mfg.
Journal, FDG PET: F-4FMFES and F-FDG PET/CT in ER+ endometrial carcinomas: preliminary report. (Pubmed Central) - May 6, 2022
It is possible to improve F-4FMFES abdominal background using hyoscine N-butylbromide. Both F-FDG and F-4FMFES-PET are suitable for detection of ER+ endometrial cancers, although F-4FMFES yielded a better tumor contrast than F-FDG.
- |||||||||| thyroxine / Generic mfg., loperamide / Generic mfg.
Journal: Drug use in patients with short bowel syndrome and intestinal failure. (Pubmed Central) - May 6, 2022
The disorder improved on a lactose and gluten-free diet, loperamide and corticosteroids. In our single-centre cohort of patients with SBS intestinal failure, orally administered medications were generally prescribed in recommended dosages.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: Effects of Maren Pills on the Intestinal Microflora and Short-Chain Fatty Acid Profile in Drug-Induced Slow Transit Constipation Model Rats. (Pubmed Central) - May 3, 2022
Loperamide hydrochloride-induced STC rats received MRW intragastrically for two consecutive weeks to evaluate the laxative effect of MRW involving the regulation of intestinal microflora, intestinal metabolism, and 5-HT signaling pathway...Finally, we found that MRW regulated the SCFA metabolism in the colonic contents of the STC rats, mainly by increasing the contents of acetic acid, propionic acid, and butyric acid; the relative abundance of Lactobacillus was positively correlated with either contents of acetic acid, propionic acid, and butyric acid, and the relative abundance of Clostridium was negatively correlated. Our study further showed that MRW could improve constipation in STC rats, and the mechanism may be by regulating the intestinal microflora structure and improving the metabolism of SCFAs.
- |||||||||| Herceptin (trastuzumab) / Roche, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Neratinib plus fulvestrant plus trastuzumab (N+F+T) for hormone receptor-positive (HR+), HER2-negative, HER2-mutant metastatic breast cancer (MBC): Outcomes and biomarker analysis from the SUMMIT trial. (Available On Demand; 406) - Apr 28, 2022 - Abstract #ASCO2022ASCO_1115;
P2
N+F+T is a promising combination for HR+, HER2-mutated MBC with prior exposure to CDK4/6i, across a range of activating HER2 mutations. Results from the upcoming Apr 2022 data cut, including biomarkers, safety, mechanisms of acquired resistance, and preclinical mechanism of N+T, will be presented.
- |||||||||| Herceptin (trastuzumab) / Roche, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Effect of traditional Chinese medicine on pyrotinib-associated diarrhea in patients with HER2-positive breast cancer. () - Apr 28, 2022 - Abstract #ASCO2022ASCO_1009;
P2
All patients in the group had diarrhea after taking pyrotinib, and they could not be controlled after previous use of other antidiarrheal drugs (loperamide, Bifidobacterium, montmorillonite powder)... TCM is very effective in the treatment of Pyrotinib related diarrhea, and compared with Western antidiarrheal drugs, it will not produce secondary painful symptoms such as constipation.
- |||||||||| Miostat (carbachol) / Novartis
Preclinical, Journal: GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. (Pubmed Central) - Apr 19, 2022
The dual inhibitory-like effects of A. nilotica on PDE and Ca were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders.
- |||||||||| imipramine / Generic mfg., loperamide / Generic mfg.
Journal: Prokinetic and Laxative Effects of Chrozophora tinctoria Whole Plant Extract. (Pubmed Central) - Apr 19, 2022
These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant...Similarly, both of the fractions showed laxative activity in metronidazole- and loperamide-induced constipation models...The present study strongly supports the folklore that this valuable plant is a cathartic agent. Further work is required to isolate and validate the bioactive compounds that act as diarrheal agents in Chrozophora tinctoria.
- |||||||||| loperamide / Generic mfg.
Preclinical, Journal: The Anti-Constipation Effects of Raffino-Oligosaccharide on Gut Function in Mice Using Neurotransmitter Analyses, 16S rRNA Sequencing and Targeted Screening. (Pubmed Central) - Apr 19, 2022
This study investigates the anti-constipation effects of ROS based on the loperamide-induced mice model and reveals the underlying mechanism using constipation parameters, neurotransmitter level, 16S rRNA sequencing, and the targeted screening strategy...In conclusion, ROS could effectively relieve constipation, possibly by inhibiting the level of neurotransmitters and regulating the gut flora in mice. This study also provides a novel network pharmacology-based targeted screening strategy to reveal the anti-constipation effects of ROS.
- |||||||||| Journal: Methicillin-resistant Staphylococcus aureus enterocolitis in a 16-month-old boy: a case report. (Pubmed Central) - Apr 19, 2022
Because methicillin-resistant Staphylococcus aureus enterocolitis is rare and has overlapping symptoms with more common gastrointestinal pathologies, it is often misdiagnosed. When a patient presents with diarrhea or high ostomy output along with fecal cultures negative for Clostridiodes difficile and other common pathogenic agents, methicillin-resistant Staphylococcus aureus should be considered.
- |||||||||| loperamide / Generic mfg.
Journal: ATF4 links ER stress with reticulophagy in glioblastoma cells. (Pubmed Central) - Apr 8, 2022
These observations highlight a key role for ATF4, RETREG1 and TEX264 in response to LOP-induced ER stress, reticulophagy and ACD, and establish a novel mechanistic link between ER stress and reticulophagy, with possible implications for additional models of drug-induced ER stress. Abbreviations: ACD: autophagic cell death; ATF6: activating transcription factor 6; ATL3: atlastin 3; BafA: bafilomycin A; CCPG1: cell cycle progression gene 1; co-IP: co-immunoprecipitation; DDIT3/CHOP: DNA damage inducible transcript 3; ER: endoplasmic reticulum; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; GABARAP: GABA type A receptor-associated protein; GBM: glioblastoma multiforme; HSPA5/BiP: heat shock protein family (Hsp70) member 5; LOP: loperamide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; RETREG1/FAM134B: reticulophagy regulator 1; RTN3L: reticulon 3 long; SEC62: SEC62 homolog, protein translocation factor; TEX264: testis-expressed 264, reticulophagy receptor; UPR: unfolded protein response.
- |||||||||| loperamide / Generic mfg.
Journal: Cardiac Electropharmacological Effects of Antidiarrheal Drug Loperamide and Its Antidote Naloxone in Anesthetized Guinea Pigs. (Pubmed Central) - Apr 5, 2022
Cardiac electropharmacological effects of an antidiarrheal drug loperamide and its antidote naloxone were assessed in isoflurane-anesthetized guinea pigs...The potency of loperamide for QT-interval prolongation was about 100-times lower than that of dofetilide, in spite that similar inhibitory effects on the human Ether-a-go-go Related Gene (hERG) K channels have been reported between loperamide and dofetilide, implying lower accessibility of loperamide to the K channels...These results suggest that loperamide has a potential to delay cardiac conduction and repolarization in the in vivo condition. Since naloxone did not modify ECG parameters and loperamide-induced ECG changes, naloxone is confirmed to possess acceptable cardiac safety when used as an antidote.
- |||||||||| loperamide / Generic mfg., pimozide / Generic mfg.
Journal: Autophagy activation, lipotoxicity and lysosomal membrane permeabilization synergize to promote pimozide- and loperamide-induced glioma cell death. (Pubmed Central) - Mar 25, 2022
The results also support the notion that simultaneous overactivation of autophagy and induction of LMP represents a promising approach for the treatment of GBM. Abbreviations: ACD: autophagic cell death; AKT1: AKT serine/threonine kinase 1; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; CERS1: ceramide synthase 1; CTSB: cathepsin B; CYBB/NOX2: cytochrome b-245 beta chain; ER: endoplasmatic reticulum; FBS: fetal bovine serum; GBM: glioblastoma; GO: gene ontology; HTR7/5-HT7: 5-hydroxytryptamine receptor 7; KD: knockdown; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; LMP: lysosomal membrane permeabilization; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; RB1CC1: RB1 inducible coiled-coil 1; ROS: reactive oxygen species; RPS6: ribosomal protein S6; SMPD1/ASM: sphingomyelin phosphodiesterase 1; VCP/p97: valosin containing protein; WT: wild-type.
- |||||||||| loperamide / Generic mfg.
Journal: An inhibitor-mediated beta cell dedifferentiation model reveals distinct roles for FoxO1 in glucagon repression and insulin maturation. (Pubmed Central) - Mar 25, 2022
Abbreviations: ACD: autophagic cell death; AKT1: AKT serine/threonine kinase 1; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; CERS1: ceramide synthase 1; CTSB: cathepsin B; CYBB/NOX2: cytochrome b-245 beta chain; ER: endoplasmatic reticulum; FBS: fetal bovine serum; GBM: glioblastoma; GO: gene ontology; HTR7/5-HT7: 5-hydroxytryptamine receptor 7; KD: knockdown; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; LMP: lysosomal membrane permeabilization; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; RB1CC1: RB1 inducible coiled-coil 1; ROS: reactive oxygen species; RPS6: ribosomal protein S6; SMPD1/ASM: sphingomyelin phosphodiesterase 1; VCP/p97: valosin containing protein; WT: wild-type. Our study provides novel models, molecular targets and drug candidates for studying and preventing beta cell dedifferentiation.
- |||||||||| verapamil / Generic mfg.
Preclinical, Journal: PET imaging to assess the impact of P-glycoprotein on pulmonary drug delivery in rats. (Pubmed Central) - Mar 23, 2022
Our results show that P-gp can affect the pulmonary disposition of inhaled P-gp substrates, whereby a decrease in P-gp activity may lead to lower lung exposure and potentially to a decrease in therapeutic efficacy. Our study highlights the potential of PET imaging with intratracheally aerosolized radiotracers to assess the impact of membrane transporters on pulmonary drug delivery, in rodents and potentially also in humans.
- |||||||||| metoclopramide / Generic mfg., apremilast / Generic mfg.
A Multinational Chart Review to Examine Gastrointestinal Symptoms and Their Management in Patients Treated with Apremilast for Plaque Psoriasis () - Mar 21, 2022 - Abstract #AAD2022AAD_2561;
The following GI symptoms were reported: ‒ Diarrhea (US: 67% [331/494]; France: 76% [97/128]) with median time from onset to resolution/improvement of 26 days (US) and 21 days (France) ‒ Nausea (US: 52% [255/494]; France: 34% [44/128]) with median time from onset to resolution/improvement of 21 days (US) and 24 days (France)Management strategies for diarrhea included pharmacologic (loperamide/bismuth subsalicylate/racecadotril) with or without non-pharmacologic (dietary modifications, taking with food)/fiber (US: 30% [99/331], France: 41% [40/97]) and non-pharmacologic only (US: 32% [105/331], France: 27% [26/97]). Recommendations to manage diarrhea and nausea after apremilast initiation with pharmacologic or non-pharmacologic strategies were effective and symptoms usually resolved within 3-4 weeks of onset.
- |||||||||| vancomycin / Generic mfg., bisacodyl / Generic mfg., loperamide / Generic mfg.
Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date: Clinical Trial to Evaluate the Efficacy of Fecal Microbiota Transplantation in Patients With Alopecia Areata (clinicaltrials.gov) - Mar 20, 2022
P2, N=0, Withdrawn,
Recommendations to manage diarrhea and nausea after apremilast initiation with pharmacologic or non-pharmacologic strategies were effective and symptoms usually resolved within 3-4 weeks of onset. N=40 --> 0 | Trial completion date: Dec 2023 --> Mar 2022 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2022 --> Mar 2022
- |||||||||| Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Effect of diarrheal prophylaxis or dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer: Final findings from the CONTROL trial (Exhibition area) - Mar 19, 2022 - Abstract #ESMOBC2022ESMO_BC_277;
P2
Legal entity responsible for the study Puma Biotechnology Inc.Funding Puma Biotechnology Inc.Neratinib (N), an irreversible pan-HER TKI, is approved in the EU for extended adjuvant treatment of early-stage HR+ HER2+ breast cancer (BC) after adjuvant trastuzumab (T)-based therapy...Pts were enrolled sequentially into separate cohorts: 1) mandatory loperamide prophylaxis; 2) budesonide + loperamide; 3) colestipol + loperamide; 4) colestipol + loperamide PRN; 5) DE + loperamide PRN (2 cohorts)...Conclusions These final findings from CONTROL show improved tolerability of N with all diarrhea prophylaxis strategies and suggest that DE1 with loperamide PRN allows pts to stay on treatm. ent longer and receive full benefit from N.
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