Effects Of Domperidone Research Articles

Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells.

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 N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo 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.

Domperidone Exerts Antitumor Activity in Triple-Negative Breast Cancer Cells by Modulating Reactive Oxygen Species and JAK/STAT3 Signaling.

The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.

A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care

Introduction The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion. Patients and methods The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes. Results A significant reduction in the viral load was observed (p < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized. Conclusion Results do not prove the use of domperidone as antiviral in patients with COVID-19.

Embryotoxicity of silica nanoparticles in the drug delivery of domperidone in zebrafish

Domperidone is a dopamine D2 receptor inhibitor that stimulates pituitary gonadotropins. It is usually associated with synthetic GnRHa to promote spawning in fish. However, the route of administration used, intramuscular injection, can be quite stressful. Little is known about the effects of domperidone, as well as other routes. This study aims to evaluate the toxicity of domperidone encapsulated by silica nanoparticles in zebrafish embryos. The study involved four groups with three concentrations: 1. domperidone (DP) 0.0001, 0.0002 and 0.0004 mg/mL; 2. DP associated with silica nanoparticles (SiNPs) 0.0001 + 1.1, 0.0002 + 2.2 and 0.0004 + 4.4 mg/mL; 3. SiNPs 1.1, 2.2 and 4.4 mg/mL and 4. Control (E3), with four repetitions per group. Survival, teratogen and heart rate (HR) were evaluated over a period of 168 hpf. Survival was higher in DP + SiNPs treatment, HR was lower in treatment with 4.4 mg/mL of SiNPs, while treatment with 0.004 mg/mL of DP increased HR. This study demonstrated that the association of DP and SiNPs decreased the toxicity of both DP and SiNPs, demonstrating that this may be a viable alternative to reduce the possible cardiotoxic effects of DP.

Effect of Domperidone on Children with Functional Abdominal Pain: A Randomized Controlled Clinical Trial

Background: One of the most common functional problems in children is functional abdominal pain (FAP), and dysmotility is one of the possible causes of FAP. Domperidone is a prokinetic drug that increases gastrointestinal motility. Objectives: The aim of this study was to evaluate the effect of domperidone on the treatment of FAP in children. Methods: In this double-blind clinical trial study, FAP was diagnosed in 80 children aged 5 - 14 years, who were referred to Amirkola Children's Hospital in Babol for one year based on the criteria of the Rome IV. Then, they were randomly divided into two groups of 40 patients. Group A received domperidone tablets (0.25 mg/kg, three-time/day) for two months, and group B received a placebo. The primary outcome was at least a 50% reduction in both frequency and severity of pain, and the secondary outcome was a significant reduction in the duration, frequency, and intensity of pain according to the Wong-Baker scale compared to baseline. Results: A total of 80 children completed the trial (40 with domperidone). The recovery rate was higher in the domperidone group than in the placebo group after eight weeks (71.8% vs. 28.2%; P &lt; 0.0001), and domperidone had significant superiority over the placebo in reducing the duration (4.58 ± 7.71 vs. 24.5 ± 41.45, min/day, P &lt; 0.001), frequency (3.35 ± 3.99 vs. 10.63 ± 10.55, episode/week, P &lt; 0.001), and intensity (2.20 ± 2.16 vs. 5.05 ± 2.37, P &lt; 0.001) of the pain. Conclusions: Based on the results, domperidone can be useful in the treatment of FAP in children.

Evaluation of domperidone efficacy to prevent aspiration pneumonia in patients with acute ischemic stroke: a randomized clinical trial.

Aspiration pneumonia is an essential complication of acute ischemic stroke (AIS), which is responsible for increased three-fold mortality within a month. There is an interest towards the effect of prokinetics on prevention of stroke-associated pneumonia. The present study aimed to investigate the effect of domperidone to prevent pneumonia in patients with AIS. In this randomized clinical trial, 150 patients with AIS were assigned to receive either domperidone 10mg daily or placebo during hospitalization. The clinical outcomes including of aspiration pneumonia occurrence, gastrointestinal discomfort, the need for intensive care unit admission, the length of hospitalization, final mRs, and mortality were then evaluated in both groups. 150 [Mean age 67.5 ± 13.5years, 90 men and 60 women] were randomized in a 1:1 ratio. Both groups were similar in terms of baseline characteristics. The domperidone group experienced significantly less dysphagia, nausea and vomiting, and aspiration pneumonia (P < 0.005). Although domperidone did not considerably reduce the mortality (P = 0.978), it resulted in lower mean mRS and shorter length of hospitalization (P < 0.001). Domperidone is an effective and well tolerated agent which could be considered as a promising agent to prevent stroke-associated pneumonia leading to a better clinical recovery.

The peripheral dopamine 2 receptor antagonist domperidone attenuates ethanol enhancement of dopamine levels in the nucleus accumbens.

Dopamine neuron firing in the ventral tegmental area (VTA) and dopamine release in the nucleus accumbens have been implicated in reward learning. Ethanol is known to increase both dopamine neuron firing in the VTA and dopamine levels in the nucleus accumbens. Despite this, some discrepancies exist between the dose of ethanol required to enhance firing in vivo and ex vivo. In the present study we investigated the effects of peripheral dopamine 2 subtype receptor antagonism on ethanol's effects on dopamine neurotransmission. Plasma catecholamine levels were assessed following ethanol administration across four different doses of EtOH. Microdialysis and voltammetry were used to assess the effects of domperidone pretreatment on ethanol-mediated increases in dopamine release in the nucleus accumbens. A place conditioning paradigm was used to assess conditioned preference for ethanol and whether domperidone pretreatment altered this preference. Open-field and loss-of-righting reflex paradigms were used to assess the effects of domperidone on ethanol-induced sedation. A rotarod apparatus was used to assess the effects of domperidone on ethanol-induced motor impairment. Domperidone attenuated ethanol's enhancement of mesolimbic dopamine release under non-physiological conditions at intermediate (1.0 and 2.0g/kg) doses of ethanol. Domperidone also decreased EtOH-induced sedation at 2.0g/kg. Domperidone did not alter ethanol conditioned place preference nor did it affect ethanol-induced motor impairment. These results show that peripheral dopamine 2 receptors mediate some of the effects of ethanol on nonphysiological dopamine neurotransmission, although these effects are not related to the rewarding properties of ethanol.

\u201cFear of stopping\u201d vs \u201cwanting to get off the medication\u201d: exploring women\u2019s experiences of using domperidone as a galactagogue - a qualitative study

BackgroundDomperidone is the most frequently prescribed medicine used to increase breast milk supply. There is considerable controversy surrounding the use of domperidone in lactation, due to limited evidence about efficacy and concerns about rare but life-threatening side-effects. Despite this, in many high-income settings such as Australia, use of domperidone among breastfeeding mothers appears to be increasing. The aim of this paper was to explore women’s experiences of using domperidone during breastfeeding.MethodsSemi-structured interviews were conducted in 2019 with 15 women in Australia who reported using domperidone as a galactagogue during breastfeeding. Interviews were recorded, transcribed and analysed thematically.ResultsWomen reported a wide variety of practices concerning the timing of initiation of domperidone use, including prophylactic use, as well as the dose and duration of use. Prolonged periods of use and unsupervised dosing were commonly reported, these practices were sometimes associated with a fear of the consequences of stopping, insufficient provision of information about the drug or feeling dismissed by health professionals. Some women indicated that when doctors refused to prescribe domperidone they responded by doctor shopping and seeking anecdotal information about benefits and risks online, leading to unsupervised practices. Women often reported high expectations surrounding the effectiveness of domperidone, and most used the medication in conjunction with food/herbal galactagogues and non-galactagogue support. Positive outcomes following domperidone use included having greater confidence in breastfeeding and pride at achieving breastfeeding goals.ConclusionsThis study identified a variety of practices concerning domperidone use, including potentially unsafe practices, linked in some cases to inconsistent advice from health professionals and a reliance on online, anecdotal information sources. These findings emphasise the urgent need for development of clinical practice guidelines and a greater focus on translating existing evidence concerning domperidone into clinical practice, including clinical support that is tailored to women’s needs.

Effect of domperidone (leisguard\xae) on antibody titers, inflammatory markers and creatinine in dogs with leishmaniosis and chronic kidney disease

BackgroundImmunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD).MethodsDogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC < 3.5 mg/dl; proteinuric or non-proteinuric]). After inclusion, an oral suspension of domperidone was administered, and the dogs were followed up for 180 days, with checks at 30, 60, 90 and 180 days after initial treatment.ResultsOf the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ2 = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ2 = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ2 = 9.56, df = 2, P = 0.008), globulins (χ2 = 11.08, df = 3, P = 0.011) and gamma globulins (χ2 = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ2 = 16.7, df = 3, P = 0.001), but not in big ET-1 (χ2 = 2.04, df = 3, P = 0.563).ConclusionsThis study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD.Graphical abstract

Impeding Virulence of Candida albicans by Candesartan and Domperidone.

Candida albicans is the most common human fungal pathogen that has developed extensive virulence factors which allows successful colonization and infection of the host. Anti-virulence agents can alleviate the pathogenesis of fungi and help the immune system to eradicate them easily. This study aimed to explore the anti-virulence effect of domperidone and candesartan against C. albicans standard strain. Sub-inhibitory concentrations (1/4 and 1/8 of minimum inhibitory concentration) of domperidone and candesartan significantly inhibited the virulence factors hemolysin, lipase, protease, phospholipase, and bioflim formation. It was found that candesartan inhibited biofilm formation by60.48-67.91%, hemolysin activity (61.21-74.14%), phospholipase activity (40-49.67%), lipase activity (58.97-73%), and protease activity (52.63%), while domperidone was found to inhibit biofilm formation by 70.54-77.49%, hemolysin activity (64.84-69.84%), phospholipase activity (49.67-60%), lipase activity (50-54.87%), and protease activity (52.63-57.9%). Quantitative real time-PCR confirmed the anti-virulence activity of domperidone and candesartan as both drugs significantly reduce the expression of the virulence genes SAP2, SAP6, PLB1, PLB2, LIP4, LIP5. In conclusion, domperidone and candesartan could serve as anti-virulence agents for treatment of C. albicans infections.

Rotigotine-loaded microspheres exerts the antinociceptive effect via central dopaminergic system

Rotigotine-loaded microspheres (RoMS), a sustained-release formulation with a continuous release of rotigotine for more than 7 days in vivo, have been conducted a clinical trial for the treatment of Parkinson's disease (PD). Previous work from our laboratory showed that RoMS exerted an antinociceptive effect in rat models of inflammatory pain. The purpose of this study was to investigate the mechanisms of action underlying the antinociceptive effect of RoMS. A rat model of inflammatory pain was prepared by an intraplantar injection of carrageenan. The hot plate test and the Randall–Selitto test were used to evaluate the effect of domperidone (selective D2 receptor antagonist), D2D3 shRNA, and naloxone (nonselective opioid receptor antagonist) on RoMS-mediated antinociceptive efficacy. The expressions of D2 and D3 receptors in the striatum and periaqueductal gray were measured by Western blotting. Intracerebroventricular injection of domperidone abated the antinociceptive effect of RoMS. However, intraperitoneal injection of domperidone had no significant effect on the antinociceptive action of RoMS. Intracerebroventricular injection with D2D3 shRNA significantly attenuated the expressions of D2 and D3 receptors in the striatum and the periaqueductal gray. D2 and D3 receptors silence significantly weakened RoMS-mediated antinociceptive effect. Intracerebroventricular injection of naloxone also alleviated the antinociceptive effect of RoMS. The results suggest that RoMS-mediated antinociceptive efficacy is associated with activating central dopamine D2 and D3 receptors. Opioid receptors play a role in the antinociceptive effect of RoMS.

Providing domperidone throughout lactation enhances sow lactation performance.

The goal of this project was to determine the effects of domperidone given throughout lactation on hormonal and metabolic status, lactational performance, and gene expression in mammary epithelial cells of sows. Second parity sows were divided in two treatment groups: 1) daily intramuscular injections with canola oil (Control, CTL, n = 24), or 2) daily intramuscular injections with 0.5 mg/kg body weight (BW) of domperidone (DOMP, n = 23). Injections were given at 08h05 starting the day after farrowing until weaning. Over the first 4 d of treatment, DOMP sows also received 0.5 mg/kg BW of domperidone per os twice daily, whereas CTL sows were fed the vehicle. Litter size was standardized to 11 ± 1 within 24 h of birth and piglets were weighed at birth, 24 h postpartum, and on days 7, 22 (weaning on day 23), 35, and 56. Sow feed intake was recorded daily. Representative milk samples were obtained aseptically on day 21 of lactation from 15 sows per treatment for compositional analyses and milk fat globules were used to measure mRNA abundances of various genes. Jugular blood samples were obtained from all sows on days 2, 8, 16, and 23 of lactation to measure concentrations of prolactin, insulin-like growth factor-1 (IGF-1), leptin, adiponectin, insulin, glucose, urea, and free fatty acids (FFA). Concentrations of prolactin (P < 0.001) and FFA (P < 0.01) were increased in DOMP compared with CTL sows, whereas concentrations of insulin were decreased (P < 0.05). Urea concentrations were increased by treatment (P < 0.05) on days 16 and 23 of lactation, and those of IGF-1 were increased (P < 0.01) on day 16. Piglets from DOMP sows were heavier than those from CTL sows on day 22 (P < 0.01). Milk composition was unaffected by treatment. The mRNA abundance in milk fat globules for casein beta and whey acidic protein were lower (P ≤ 0.05) in DOMP than CTL sows. The long form of the prolactin receptor and the signal transducer and activator of transcription 5A mRNA abundances tended to be lower (P < 0.10) in DOMP than CTL sows. In conclusion, hyperprolactinemia induced by domperidone during lactation affected the endocrine and metabolite status of sows and stimulated growth of their suckling piglets.

Efficacy and Safety of Domperidone and Metoclopramide in Breastfeeding: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the efficacy and safety of domperidone and metoclopramide used by breastfeeding women. Methods: A systematic literature search retrieved citations from PubMed, Embase, The Cochrane Library, Medline, EBSCO, Web of Science, ClinicalTrials.gov (from inception to January, 2021) and bibliographies of known articles. Randomized controlled trials exploring the effects of domperidone and metoclopramide in breastfeeding women with term and preterm infants experiencing adequate or low milk supply were identified. Human milk volume and maternal side effects were presented as mean difference (MD) or relative risks (RR) with 95% confidence intervals (CI). Results: Sixteen trials involving 729 women were included in the qualitative analysis and 14 trials involving 607 women were included in the meta-analysis. In mothers of preterm infants with low milk supply, domperidone demonstrated a significant increase in daily human milk volume (MD = 90.53 mL/day, 95% CI [65.42 to 115.64], I2 = 9%). However, metoclopramide did not show significant difference in daily human milk volume in women with preterm infants (MD = -1.14 mL/day, 95% CI [-31.42 to 29.14], I2 = 0%). No differences in maternal side effects were noted with domperidone (RR = 1.20, 95% CI [0.74 to 1.97], I2 = 0%) or metoclopramide (RR = 1.05, 95% CI [0.52 to 2.11], I2 = 27%) in women with preterm infants. Regarding the women with term infants, there were insufficient data in the current review. Conclusions: Domperidone can be used to treat low milk supply in women with preterm infants without significant side effects based on the current review. More evidence exploring the efficacy and safety of domperidone and metoclopramide are still needed for breastfeeding women in the future.

Can domperidone decrease transit time of pediatric video capsule endoscopy? A randomized controlled trial.

BackgroundThe complete examination rate of video capsule endoscopy can be increased by reduced gastric transit time (GTT) and or small bowel transit time (SBTT). This study aims to examine whether the prokinetic domperidone reduces GTT and/or SBTT in pediatric patients undergoing video capsule endoscopy (VCE).MethodsWe performed a single-center randomized controlled trial (n=200) to evaluate the effect of domperidone on GTT and SBTT among pediatric patients in a tertiary university-affiliated hospital for children. We explored whether patients randomized to domperidone had increased GTT, SBTT (primary outcomes) or higher complete examination rate (secondary outcome). The safety outcomes were the adverse effects in the domperidone group. This study was registered on ClinicalTrials.gov (NCT03662113).ResultsDemographic features including gender and age were similar between the 100 patients of the domperidone group and the 100 patients of the control group. The median GTT was 67.5 minutes (44.8–117.5) in the domperidone group and 80.0 minutes (42.0–128.0) in the control group, while the median SBTT was 317 minutes (231–436) and 323 minutes (225–426), respectively. There were no significant differences in GTT (P=0.49) and SBTT (P=0.52) between the two groups. The complete examination rate was 97% and 98% in the domperidone and control groups, respectively (P=1.00).ConclusionsDomperidone shows no effect on GTT, SBTT and complete examination rate in pediatric patients receiving VCE.

Effect of domperidone, ondansetron, olanzapine-containing antiemetic regimen on QTC interval in patients with malignancy: a prospective, observational, single-group, assessor-blinded study

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ2(4) = 15.629, p = 0.004; Bazett, χ2(4) = 15.910, p = 0.003); QTc on Day 1 was more than that during baseline (p < 0.001); these differences were significant in females (Fridericia, χ2(4) = 13.753, p = 0.008; Bazett, χ2 (4) = 13.278, p = 0.010) but not in males (Fridericia, χ2 (4) = 4.419, p = 0.352; Bazett, χ2(4) = 4.280, p = 0.369). Two female patients had an absolute QTc prolongation (Bazett correction) of > 500 ms. However, no clinically significant adverse events occurred. The findings show that QTc prolongation is a concern with olanzapine alone and in combination with domperidone and ondansetron, and needs to be investigated further.

A Causal Role for Gastric Rhythm in Human Disgust Avoidance

SummaryRotten food, maggots, bodily waste—all elicit disgust in humans. Disgust promotes survival by encouraging avoidance of disease vectors1 but is also implicated in prejudice toward minority groups; avoidance of environmentally beneficial foods, such as insect protein; and maladaptive avoidance behavior in neuropsychiatric conditions.2, 3, 4, 5 Unlike fear, pathological disgust is not improved substantially by exposure therapy clinically,6 nor in experimental work does behavioral avoidance of disgusting images habituate following prolonged exposure.7,8 Under normal physiological conditions, perception of disgusting stimuli disrupts myoelectrical rhythms in the stomach,9, 10, 11, 12, 13 inducing gastric dysrhythmias that correlate with neural signatures of disgust.11 However, the causal role of gastric rhythm in disgust avoidance is unknown. We manipulated gastric rhythm using domperidone, a peripheral dopamine D2/D3 antagonist and common anti-emetic, at a dose (10 mg) that acts to convert gastric dysrhythmias to normal rhythms.9 In a preregistered, randomized, double-blind, placebo-controlled crossover design in 25 healthy volunteers (aged 18–25), we measured the effects of domperidone on core disgust avoidance, using eye tracking to measure implicit (oculomotor) avoidance of disgusting images (feces) before and after an “exposure” intervention (monetary reinforcement for looking at disgusting images).7,8 We find that domperidone significantly reduces oculomotor disgust avoidance following incentivized exposure. This suggests that domperidone may weaken the “immunity” of disgust to habituation, putatively by reducing gastric dysrhythmias during incentivized engagement with disgusting stimuli. This indicates a causal role for disgust-related visceral changes in disgust avoidance, supporting the hypothesis that physiological homeostasis contributes to emotional experience.

Effect of Domperidone on Breast Milk Production in Mothers of Sick Neonates: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Objective: Mothers of many preterm babies are unable to produce sufficient milk for their babies during the prolonged hospitalization. Domperidone stimulates the release of prolactin, thereby increasing breast milk production. The primary outcome was to study the efficacy of domperidone in augmenting breast milk production in mothers with lactation failure (LF). The secondary outcomes included the effect of domperidone on prolactin levels, adverse effects of domperidone, and outcome on breastfeeding rates at discharge. Materials and Methods: This was a randomized, double-blinded, placebo-controlled trial where mothers with LF were either allocated domperidone (10 mg) or placebo, 2 tablets three times a day for 14 days. Milk volumes were recorded daily for 14 days. Serum prolactin levels were measured at the start and at day 7 of study. Results: Out of 166 women eligible for the study, 119 (71.7%) mothers were able to increase their breast milk production without pharmacological treatment after being counseled on the advantages of human milk and proper breastfeeding management. Forty-seven mothers were finally enrolled in the study; 24 in the domperidone group (DG) and 23 in the placebo group (PG). Breast milk production increased from a baseline of 156 + 141.1 to 400.9 + 239.2 mL in the DG and increased from a baseline of 175.8 + 150.7 to 260.5 + 237.5 mL in the PG, after 14 days (p < 0.01). The prolactin levels in the DG and PG increased from 72.85 (22.2-167.15) and 42.33 (14.02-93.54) ng/mL, respectively, to 223.4 (49.79-280.2) ng/mL (p = 0.005) in the DG and 60.08 (14.31-132.14) ng/mL (p = 0.232) in the PG on the 7th day of treatment. No adverse effects were recorded. Ninety-five percent of babies in the DG were exclusively breastfeeding at hospital discharge, compared with 52.4% in the PG (p = 0.008). Conclusion: Domperidone treatment can result in an increase in breast milk production with no adverse effects. The study was registered with the Thai Clinical Trials Registry ID TCTR2020091008.

Domperidone induced galactorrhea: rare presentation of a common drug

Domperidone is one of the cheapest and also effective anti-emetic drugs which is very commonly used as an over-the-counter drug. Galactorrhoea is a rare side effect of domperidone. We report a case of a female patient who was prescribed domperidone for migraine headache with vomiting. While taking the drug, she developed galactorrhoea, and after discontinuing domperidone therapy, her galactorrhoea subsided.

S0473 Domperidone Is Superior Compared With Metoclopramide in Improving Gastroparesis Symptoms: A Systematic Review and Meta-Analysis

INTRODUCTION: Gastroparesis (GP) is a syndrome presenting with refractory nausea, vomiting, early satiety, and bloating in the setting of delayed gastric emptying (GE) in the absence of mechanical obstruction. Medical management of GP is difficult, and the outcome is often poor. Metoclopramide (MCP) and domperidone are antiemetics and prokinetics with antidopaminergic activities. They produce their antiemetic effects through the chemoreceptor trigger zone, and they function as prokinetics by blocking dopamine in the stomach and proximal duodenum. Unlike domperidone, MCP is permeable to the blood-brain barrier and has a “black box” warning for tardive dyskinesia. However, domperidone is only prescribed under an Investigational New Drug protocol in the United States, mainly due to scattered reports of cardiac events related to prolonged QTc interval. In this meta-analysis, the authors sought to compare the effects of MCP and domperidone for improving GP symptoms. METHODS: A search in PubMed, Embase, American College of Gastroenterology, and Digestive Disease Week abstracts database was performed to find trials on MCP and domperidone in GP. Direct and indirect comparisons of GP symptom and GE improvement with MCP and domperidone were pooled and were reported as mean (standard deviation). Random effects model was used in this meta-analysis to overcome limitations related to heterogeneity. RESULTS: Response to MCP (3-6 weeks treatment), domperidone (4 weeks to 4 years), and domperidone vs MCP (4 weeks treatment) were examined in 5, 10, and 1 (Patterson 1999) published studies, respectively. Overall, 99 and 421 GP patients received MCP and domperidone, respectively. MCP had an overall symptom improvement rate of 48.8 (95% CI: 38.8–58.70) compared with 63.6 (95% CI: 55.1–71.7) (P < 0.05) improvement in domperidone-treated groups (Figures 1 and 2). MCP and domperidone improved GE by 19.7 (SD: 6.6) and 30.7% (SD: 13.9), respectively (P > 0.05) involving different methodologies. No major adverse events, including acute coronary syndrome, serious arrhythmias, or cardiac death were reported with domperidone. Most recent studies provided QTc values which did not show any clinically significant QTc prolongation. CONCLUSION: Domperidone demonstrates significant superiority compared to MCP. It is safe and effective in GP when administered under monitored conditions. Promotility effects of domperidone are complemented by its powerful antiemetic properties providing a clinically valuable symptom control in GP patients.Figure 1.: Pooled overall gastroparesis symptom improvement rate after metoclopramide treatment.Figure 2.: Pooled overall gastroparesis symptom improvement rate after domperidone treatment.

S3027 Breast Milk Fistula: An Unusual Complication of Therapy for Gastroparesis

INTRODUCTION: We report an unusual medication related complication that developed in a patient being treated for chronic idiopathic gastroparesis. CASE DESCRIPTION/METHODS: The patient, a 40-year-old female, has a long history of idiopathic gastroparesis. Symptoms have been present for many years and in the past resulted in weight loss and numerous hospital visits. Gastric emptying scans have been markedly abnormal and on endoscopic examination residual old food was always present in the stomach. She had been evaluated for a possible gastric pacemaker and she has had pyloric Botox injections, pyloric dilation and has been treated with metoclopramide and more recently with domperidone for the last few years. She had also had a Nissen fundoplication for chronic reflux associated with gastric stasis. Her condition has remained stable for many months and she has gained weight and not required hospital visits. She presented to a breast surgeon with a recurrent chronic right breast abscess with overlying necrotic skin. Breast exam revealed no nipple discharge at that time, and she went to surgery for exploration, drainage and debridement. One week post procedure she complained of malodorous drainage from the incision and serous drainage was noted on the dressing. Wound culture was obtained and grew rare Streptococcus anginosis. The patient was started on Bactrim and a wick and plain packing was placed. Eleven days later she presented to the emergency room with complaints of malodorous drainage and right breast pain. Ultrasound revealed 3.1 × 0.7 × 3.5 cm complex fluid collection. Culture grew rare gram-positive cocci in pairs. She was treated with clindamycin and discharged home. She was reevaluated by the surgeon and new left nipple drainage was noted. Wound healing remained impaired. This raised the question of a milk fistula. The patient was instructed to stop taking domperidone. Over the next weeks the wound closed and there was no further drainage. She subsequently resumed her domperidone. DISCUSSION: Galactorrhea can be an uncommon side effect of domperidone. In this case it led to an unusual complication of breast wound milk fistula delaying healing of an abscess.