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Cureus Dec 2023The commonest medications prescribed in functional dyspepsia are prokinetic agents, specifically domperidone. However, its administration at times elevates serum...
The commonest medications prescribed in functional dyspepsia are prokinetic agents, specifically domperidone. However, its administration at times elevates serum prolactin levels, which can lead to pathological hyperprolactinemia. The present study investigated the effect of 28 days of 30 mg domperidone therapy on prolactinemia in functional dyspepsia patients. We recruited 97 patients (60 men and 37 women, aged 18-80 years) who had functional dyspepsia diagnosed as per the Rome IV criteria. After taking a preliminary clinical history, we measured and compared serum prolactin levels at day 'zero' and day 'twenty-eight'. We found increased prolactin levels from day '0' to day '28' after treatment with domperidone in functional dyspepsia patients, specifically in male participants aged less than 40 years, who are married and belong to middle socioeconomic status. The most common functional dyspepsia symptom found was pain in the epigastric region. To conclude, our pragmatic domperidone-induced-hyperprolactinemia link warrants this side effect to be robustly taken into account while treating functional dyspepsia patients with domperidone.
PubMed: 38249246
DOI: 10.7759/cureus.50927 -
Cureus Oct 2023Background Acute gastroenteritis (AGE) is a major health concern in pediatric populations because of its associated vomiting, which worsens dehydration and the severity...
Background Acute gastroenteritis (AGE) is a major health concern in pediatric populations because of its associated vomiting, which worsens dehydration and the severity of illness. Objective The purpose of the research was to compare the relative effectiveness of oral ondansetron in treating AGE in children's vomiting when compared to oral domperidone and oral metoclopramide. Methodology A clinical investigation involving 120 pediatric patients diagnosed with AGE was conducted in Pakistan from November 2022 to April 2023 using a single-blind randomized design and convenience sampling. The participants received oral suspensions of ondansetron, metoclopramide, and domperidone, with doses of 0.15 mg/kg, 0.1-0.2 mg/kg, and 0.5 mg/kg, respectively, adjusted according to their body weight. The outcome in different groups was analyzed using the Statistical Package for the Social Sciences (SPSS) (version 20.0; IBM SPSS Statistics for Windows, Armonk, NY). Results At six hours, vomiting cessation rates were 80.0% for ondansetron (n=32), 72.5% for domperidone (n=29), and 67.5% for metoclopramide (n=27; p=0.29). By 24 hours, ondansetron exhibited significantly higher efficacy (92.5%; n=37) compared to domperidone (82.5%; n=33) and metoclopramide (77.5%; n=31; p=0.03). Adverse effects were minimal and comparable across groups. Conclusion Oral ondansetron demonstrated superior efficacy in managing AGE-related vomiting in children within 24 hours compared to metoclopramide and domperidone.
PubMed: 38022212
DOI: 10.7759/cureus.47611 -
BMJ Paediatrics Open Nov 2023This study aims: (a) to evaluate patterns of domperidone dispensing to mothers of very preterm (<32 weeks gestation) infants born before and after 2014 when...
OBJECTIVE
This study aims: (a) to evaluate patterns of domperidone dispensing to mothers of very preterm (<32 weeks gestation) infants born before and after 2014 when international recommendations were made to limit its use and (b) to examine characteristics associated with domperidone dispensing and impacts on breast milk feeding rates at infant hospital discharge.
DESIGN
Retrospective audit using linked electronic medical records and hospital pharmacy records.
SETTING
Tertiary-referral neonatal intensive care unit at the Women's and Children's Hospital in South Australia.
PATIENTS
Mothers of preterm infants admitted to neonatal intensive care from January 2004 to December 2018.
MAIN OUTCOME MEASURES
Rate of domperidone dispensing compared pre-2014 and post-2014 recommendations using interrupted time series analyses, and breast milk feeding rates at infant discharge based on domperidone treatment status, adjusted for other factors known to influence breast milk production.
RESULTS
Overall, domperidone was dispensed to 691 (41%) of 1688 mothers. Prior to 2014 recommendations, the proportion of women dispensed domperidone was stable. Following the recommendations, there was a significant reduction in trend (-2.55% per half year, 95% CI -4.57% to -0.53%;), reflecting less domperidone dispensing.Breast milk feeding rates at discharge remained consistently lower in infants of women dispensed domperidone than those who were not (adjusted OR 0.58, 95% CI 0.45 to 0.75).
CONCLUSION
Domperidone dispensing in mothers of hospitalised very preterm infants has declined over time following international regulatory warnings. Breast milk feeding rates remain lower in mothers prescribed domperidone, suggesting further research is needed to optimise lactation support for mothers of very preterm infants.
Topics: Child; Infant; Humans; Infant, Newborn; Female; Domperidone; Milk, Human; Retrospective Studies; Lactation; Infant, Premature; Patient Discharge
PubMed: 37923344
DOI: 10.1136/bmjpo-2023-002195 -
Biomolecules & Therapeutics Jun 2024Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is...
Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase- 3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways, respectively. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and -acetylcysteine treatment mitigated ROS levels and restored cell viability. An xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.
PubMed: 38914471
DOI: 10.4062/biomolther.2024.048 -
Gynecologic Oncology Sep 2023Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRβ2, DRD1 and DRD2 expression in healthy...
OBJECTIVE
Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRβ2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy.
METHODS
109 EC patients were included. The expression of the ADRβ2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability.
RESULTS
ADRβ2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa).
CONCLUSION
DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.
Topics: Female; Humans; Prognosis; Receptors, Dopamine D2; Endometrial Neoplasms
PubMed: 37437489
DOI: 10.1016/j.ygyno.2023.06.019 -
Journal of Ethnopharmacology Mar 2024Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear.
ETHNOPHARMACOLOGICAL RELEVANCE
Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear.
AIM OF THE STUDY
To elucidate the mechanism underlying the efficacy of Liansu capsule in alleviating FD symptoms.
MATERIALS AND METHODS
Thirty-six male mice were randomly divided into the following six groups: control, model, low-strength Liansu, moderate-strength Liansu, high-strength Liansu, and domperidone groups. Small intestine propulsion rate, gastric residual rate and histopathological analysis were performed to evaluate efficacy of Liansu capsule. Levels of interleukin-1β, interleukin-6, tumor necrosis factor α, phosphorylation of p65, ghrelin and gastrin were verified by real-time quantitative polymerase chain reaction and immunofluorescence assays. Targeted metabolomic analyses, western blotting and immunofluorescence assays were used to explore the mechanism of Liansu capsule in ameliorating FD.
RESULTS
The Liansu capsule significantly ameliorated the symptoms of FD, and markedly increased the levels of ghrelin and gastrin. Moreover, Liansu capsule significantly downregulated the levels of the proinflammatory cytokine interleukin-1β, interleukin-6, tumor necrosis factor α, and inhibited the phosphorylation of p65. Targeted metabolomic analyses showed that Liansu capsule significantly reduced the levels of deoxycholic acid and hyodeoxycholic acid, which were significantly elevated in the model group. Furthermore, these results showed that deoxycholic acid and hyodeoxycholic acid markedly promoted the levels of Takeda G-protein-coupled receptor 5 (TGR5), phosphorylated signal transducer and activator of transcription 3 (STAT3), and Kruppel-like factor 5 (KLF5) in vitro. whereas, Liansu capsule significantly reduced the levels of TGR5, phosphorylated STAT3, and KLF5.
CONCLUSION
Our findings indicated that Liansu capsule improved FD by regulating the deoxycholic acid/hyodeoxycholic acid-TGR5-STAT3-KLF5 axis. The findings reveal a novel mechanism underlying the role of Liansu capsule, which may be a promising therapeutic strategy for FD.
Topics: Male; Mice; Animals; Dyspepsia; Ghrelin; Tumor Necrosis Factor-alpha; Gastrins; Interleukin-6; Interleukin-1beta; Deoxycholic Acid
PubMed: 38092317
DOI: 10.1016/j.jep.2023.117568 -
Endocrinology, Diabetes & Metabolism... Oct 2023With rising rates of adoption and surrogacy, induced lactation is likely to become increasingly relevant, allowing women who did not undergo pregnancy to breastfeed. We...
SUMMARY
With rising rates of adoption and surrogacy, induced lactation is likely to become increasingly relevant, allowing women who did not undergo pregnancy to breastfeed. We describe the case of a woman with complete androgen insensitivity syndrome (CAIS) on conventional oestrogen therapy who was expecting a child via surrogacy and who wished to breastfeed. The woman was commenced on supplementary oestrogen therapy, domperidone and breast stimulation by mechanical breast pump 8 weeks prior to the delivery of her child. Following delivery, the patient produced a small, unquantified amount of milk, allowing her to suckle the infant for a short period of time. Induced lactation is possible in chromosomally XY individuals. It has been most successful in cis-women and transwomen, both of whom have had progesterone/progestogen exposure to the breast. We suggest that the addition of a progestogen to our patient's treatment regimen, either as part of her original hormone therapy or part of the lactation induction program, would have improved her changes of establishing successful lactation.
LEARNING POINTS
Induced lactation is possible in chromosomally XY individuals with the use of pharmacological and non-pharmacological therapies. There are no standardised guidelines regarding the optimal regimen for induced lactation. Progesterone exposure to the breast is essential for ductal branching and alveolar maturation. In the published literature, induced lactation is more successful in transwomen and other XY individuals who have had prior progesterone exposure. The addition of progestogen to our patient's treatment regimen would have improved her chances of establishing successful lactation.
PubMed: 37965919
DOI: 10.1530/EDM-23-0063 -
Heliyon Feb 2024The current research proposed a highly sensitive and selective spectrofluorometric approach for the assay of gastrointestinal medications omeprazole (OMZ) and...
The current research proposed a highly sensitive and selective spectrofluorometric approach for the assay of gastrointestinal medications omeprazole (OMZ) and domperidone (DOM). Green synthesis of metal oxide nanoparticles such as zinc oxide (ZnONPs) and cerium oxide (CeONPs) using and extract was used as fluorescence emission catalysts for the determination of OMZ and DOM. Due to their unique optical properties, nanoparticles (NPs) form the basis for spectrofluorimetric quantification of the selected drugs. The detection studies were performed under λex/λem 350/450 nm and 284/392 nm for OMZ and DOM in the presence of ZnONPs and CeONPs, respectively. Under ideal conditions, fluorescence intensities (FI) were linearly with correlation coefficient (r = 0.999) over concentration ranges of 0.1-100 and 0.01-200 μg mL for OMZ, 0.01-100 and 0.01-300 g mL for DOM in the presence of ZnONPs and CeONPs, respectively. Method validation was carried out to guarantee the accuracy, suitability, and precision of the proposed fluorescence (FL) systems for the determination of OMZ and DOM. Analytical method guidelines and requirements were followed. The designed procedure was used effectively to identify the determined drugs in both their pure and commercial versions.
PubMed: 38390119
DOI: 10.1016/j.heliyon.2024.e26164 -
Heliyon Sep 2023Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which...
Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.
PubMed: 37809676
DOI: 10.1016/j.heliyon.2023.e19904 -
Cancer Cell International Mar 2024Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive...
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate.
METHODS
A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone.
RESULTS
After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC.
CONCLUSION
Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.
PubMed: 38528618
DOI: 10.1186/s12935-024-03291-8