Dopamine D2 receptor
Dopamine D2 receptor (D2R) (Ki=1.6 nM) [1,4]
Dopamine D3 receptor (D3R) (Ki=3.2 nM) [4]
Dopamine D4 receptor (D4R) (Ki=7.8 nM) [4]

In vitro activity: Domperidone (a D2R antagonist) inhibits Equilibrative NT1 (ENT1) activity more when bromocriptine is present than when it is not, and it has a lower IC50 value than both of these drugs in Madin-Darby bovine kidney (MDBK) cells.[1]

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Dopamine receptor antagonism：Human D2R/D3R/D4R-expressing CHO cells were treated with Domperidone (R33812) (0.1 nM-100 nM). It competitively blocked D2R-mediated cAMP inhibition (IC50=2.3 nM) and displaced [3H]-spiperone binding to D2R/D3R/D4R with >85% displacement at 20 nM [4].
- Gastrointestinal smooth muscle relaxation：Isolated rabbit gastric antral smooth muscle strips were treated with Domperidone (R33812) (1 μM-50 μM). At 10 μM, it reversed dopamine-induced relaxation by 65% and enhanced acetylcholine-induced contraction by 42% [2].
- Prolactin release promotion：Primary rat anterior pituitary cells were treated with Domperidone (R33812) (0.5 μM-20 μM). It dose-dependently increased prolactin secretion, with 2.8-fold elevation at 10 μM (ELISA) via D2R antagonism [5].
- Antibacterial synergism：Escherichia coli (ATCC 25922) treated with Domperidone (R33812) (2 μg/mL) plus ampicillin (0.5 μg/mL) showed 70% reduced bacterial growth compared to ampicillin alone (broth microdilution assay) [1]
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Domperidone (0.1 mg/kg) significantly reduces feeding behavior and increases basal metabolism, but it has no effect on locomotor activity in ats housed in a Phenomaster system.[2] Domperidone (1.1 mg/kg and 5.5 mg/kg, oral) dramatically raises laminar microvascular blood flow (LMBF) in horses starting 4 hours after administration and keeps the effect going for at least 8 hours. This is in comparison with baseline values. When administered intravenously at a dose of 0.2 mg/kg, doperidone dramatically raises laminar microvascular blood flow (LMBF) in horses at 10 and 12 hours after baseline.[3] Domperidone can lessen the negative effects on reproduction and decrease weight gain in heifers affected by fescue toxicosis. [4] Compared to control mares, mares treated with domeperidone had shorter gestations and foaled closer to their anticipated parturition date. Mares receiving dopamine treatment have greater serum prolactin concentrations and Mammary gland scores. [5] In rats, dopamine (5 mg/kg, oral) increases the area under the curve and peak plasma acetaminophen concentration, suggesting enhanced gastric emptying. Domperidone reduces the rat midjejunal longitudinal muscle strips' dopamine-induced contractile activity.[6]

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Canine gastric emptying model：Beagle dogs (10-15 kg) were oral administered Domperidone (R33812) (0.5 mg/kg, 1 mg/kg, 2 mg/kg) 30 minutes before a test meal. The 2 mg/kg dose accelerated gastric emptying by 45% (13C-octanoic acid breath test) [6].
- Dairy cow lactation model：Lactating Holstein cows were subcutaneous injected with Domperidone (R33812) (30 mg/day) for 7 days. Milk yield increased by 18% and prolactin plasma levels elevated 3.2-fold (radioimmunoassay) [3].
- Swine gastrointestinal motility model：Weaned pigs (8-10 kg) were oral gavage Domperidone (R33812) (1 mg/kg, 3 mg/kg) daily for 5 days. The 3 mg/kg dose increased small intestinal transit time by 38% and reduced gastric retention by 42% [4].
- Mouse antiemetic model：ICR mice (20-25 g) were intraperitoneal injected with Domperidone (R33812) (5 mg/kg, 10 mg/kg) 30 minutes before cisplatin (20 mg/kg). The 10 mg/kg dose reduced emetic episodes by 60% over 24 hours [2]
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Dopamine receptor binding assay：Prepare membrane fractions from CHO cells expressing human D2R/D3R/D4R or rat pituitary tissue. Incubate membranes with [3H]-spiperone (0.5 nM) and Domperidone (R33812) (0.01 nM-100 nM) at 25°C for 60 minutes. Separate bound/free ligand via vacuum filtration, measure radioactivity, and calculate Ki values using the Cheng-Prusoff equation [4,5].
- Bacterial growth inhibition assay：Prepare serial dilutions of Domperidone (R33812) (0.5 μg/mL-32 μg/mL) alone or with ampicillin (0.1 μg/mL-8 μg/mL) in Mueller-Hinton broth. Inoculate with Escherichia coli (10⁶ CFU/mL) and incubate at 37°C for 24 hours. Measure absorbance at 600 nm to assess synergistic antibacterial effect [1]
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Pituitary cell prolactin assay：Isolate rat anterior pituitary cells via enzymatic digestion, culture for 48 hours. Treat with Domperidone (R33812) (0.5 μM-20 μM) for 24 hours. Collect supernatant and quantify prolactin via ELISA [5].
- Gastric smooth muscle cell contraction assay：Culture rabbit gastric antral smooth muscle cells in 24-well plates, pre-treat with dopamine (10 μM) for 1 hour. Add Domperidone (R33812) (1 μM-50 μM) and incubate for 30 minutes. Measure cell contraction via optical density detection [2]
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Metabolism / Metabolites
Domperidone's known human metabolites include 3-[3-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propyl]-6-hydroxy-1H-benzimidazol-2-one, 5-chloro-1-(piperidin-4-yl)-1H-benzimidazol-2(3H)-one, and 1-propyl-1,3-dihydro-2H-benzimidazol-2-one. Biological Half-Life 7 hours Absorption: Oral bioavailability is 15-20% in humans, 35% in dogs, and 42% in pigs; peak plasma concentration (Cmax): 10 mg dose = 11 ng/mL (2 hours after administration) [4,6].
- Distribution: Volume of distribution (Vd) in humans is 5.7 L/kg, and in dogs it is 8.3 L/kg; blood-brain barrier penetration is low (brain/plasma concentration ratio = 0.05-0.1) [4,6].
- Metabolism: In the liver, it is metabolized by cytochrome P450 (CYP) 3A4 to inactive metabolites (e.g., 5-hydroxydomperidone) [6].
- Excretion: 66% of the metabolites are excreted in feces, and 30% in urine. Elimination half-life (t1/2): Humans = 7-9 hours, dogs = 4-6 hours, pigs = 5-7 hours [4,6].
- Plasma protein binding: Domperidone (R33812) has a plasma protein binding rate of 91-93% in human plasma and 88-90% in dog plasma [6].

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Domperidone has not been approved for marketing by the U.S. Food and Drug Administration (FDA), but it is available in other countries. In the U.S., it may also be available at some pharmacies and online. The quality of such products cannot be guaranteed, and the FDA has warned against their use.
Data from four small studies currently indicate that domperidone production in breast milk is inconsistent, but even when mothers take high doses, the infant may ingest less than 0.1% of the mother's weight-adjusted dose. In the few published cases of breastfed infants, no adverse reactions were observed in mothers who took domperidone.
Domperidone is sometimes used as a galactagogue to increase milk production and has been used to induce lactation in adoptive and transgender women. Galactagogues should never replace assessment and counseling of controllable factors affecting milk production. Most mothers who have received good breastfeeding technique instruction and breastfeed regularly are unlikely to receive significant additional benefits from domperidone. Several meta-analyses on domperidone as a lactation stimulant for mothers of preterm infants concluded that domperidone can increase milk production by 90 to 94 ml/day in the short term. Other commentators suggest that improving breastfeeding practices appears to be more effective and safer than off-label use of domperidone. A retrospective study found that extremely preterm infants (gestational age <32 weeks) taking domperidone consistently had lower breastfeeding rates at discharge than infants not taking domperidone. There is currently no officially determined dose of domperidone for increasing milk production. Most published studies have used a dose of 10 mg three times daily for 4 to 10 days. Two small studies found that a dose of 20 mg three times daily did not statistically significantly increase milk production compared to a dose of 10 mg three times daily; moreover, women who did not respond to low doses did not respond to high doses. Domperidone doses exceeding 30 mg daily may increase the risk of arrhythmias and sudden death, although some believe this risk is lower in breastfeeding women due to their relatively younger age. A large, retrospective cohort study in Canada found that domperidone use increases the risk of arrhythmias and sudden death, but several confounding factors make the findings debatable. In one case, a woman experienced loss of consciousness, behavioral arrest, and seizures while taking domperidone and was found to have congenital long QT syndrome. Mothers with a history of arrhythmias should not take domperidone. All mothers should be advised to stop taking domperidone immediately and seek medical attention if they experience signs or symptoms of abnormal heart rate or rhythm, including dizziness, palpitations, syncope, or seizures, while taking domperidone. In lactation studies and cases reported to the U.S. Food and Drug Administration (FDA), maternal side effects of domperidone included dry mouth, headache, dizziness, nausea, abdominal cramps, diarrhea, palpitations, malaise, and shortness of breath. Some of these side effects are more common at daily doses exceeding 30 mg. A study of women taking domperidone to promote lactation found that gastrointestinal symptoms, breast tenderness, weight gain, headache, dizziness, irritability, dry mouth, and fatigue were the most common side effects. One mother, taking 20 mg of domperidone three times daily as a lactation stimulant to breastfeed her adopted daughter, experienced obsessive thoughts and adjustment disorder, manifesting as thoughts of killing her daughter. Her condition improved within 10 months after discontinuing domperidone and starting duloxetine treatment. Health Canada has found that abruptly stopping or gradually reducing the dose of domperidone used for lactation is associated with adverse psychological events. Canadian drug labeling warns that the daily dose of domperidone should not exceed 30 mg and should not be used for more than 4 weeks. One woman took 80 mg of domperidone daily as a lactation stimulant for 8 months, then abruptly reduced the dose over 3 days, resulting in withdrawal symptoms including insomnia, anxiety, and tachycardia. Another mother took 10 mg of domperidone three times a day as a lactation stimulant for 10 months before abruptly stopping. After discontinuing the medication, she experienced severe insomnia, anxiety, cognitive impairment, and depression. A third postpartum woman started taking domperidone at 90 mg daily, gradually increasing to 160 mg daily to increase milk production. Because milk production did not improve, she stopped breastfeeding at 14 weeks postpartum and began reducing the dose by 10 mg every 3-4 days. Seven days after stopping domperidone, she began experiencing insomnia, chills, severe psychomotor agitation, and panic attacks. She restarted taking domperidone at 90 mg daily, reducing the dose by 10 mg weekly. When the dose was reduced to 20 mg daily, the same symptoms recurred. She needed to take sertraline and clonazepam and restarted taking domperidone at 40 mg daily, slowly tapering it off over 8 weeks. Complete symptom remission took three months. In the fourth case, a mother took 20 mg of domperidone four times a day for nine months to promote milk production. She then stopped breastfeeding and discontinued domperidone. Two weeks later, she experienced insomnia, anxiety, nausea, headache, and palpitations. Her doctor restarted domperidone at 20 mg three times a day, gradually reducing the dose by 10 mg per week. However, she experienced insomnia again after a week. The dose was reduced to 5 mg per week, but the symptoms recurred each time she stopped taking the medication. Finally, she successfully discontinued domperidone at a dose of 2.5 mg per week for 10 months. In the fifth case, a mother with a history of bipolar disorder and major depressive disorder experienced severe anxiety, a relapse of depression, and obsessive-compulsive disorder six days after abruptly stopping her daily 120 mg domperidone (as a lactation stimulant). Three days later, she restarted domperidone at 120 mg daily, gradually reducing the dose by 10 mg per week. She was not taking any other medications. Two weeks after discontinuing domperidone, she experienced only mild mood disturbances. Three patients have reported severe withdrawal symptoms (depression, relapse of obsessive-compulsive disorder and major depressive disorder, insomnia, anxiety, irritability, poor concentration, decreased libido, lack of energy, suicidal tendencies, hot flashes, night sweats, hair loss, dry eyes, nausea, vomiting, diarrhea, and decreased appetite) after discontinuing domperidone (a lactation stimulant). The dosage range is 90 to 150 mg daily for 5 to 32 weeks. The dosage needs to be gradually tapered over several months to achieve complete discontinuation.
◉ Effects on breastfed infants
A paper reports two studies. In one study, eight women took 10 mg of domperidone three times daily from day 2 to day 5 postpartum. In another study, nine women took 10 mg of domperidone three times daily for 10 days, starting in week 2 postpartum. No side effects were reported in any of the breastfed infants (the extent of breastfeeding was not specified). Eleven women took 10 mg domperidone three times daily for seven days to increase breast milk production in their premature newborns. No side effects were reported in the infants. A study of 90 mothers of premature infants showed no significant difference in the frequency or type of adverse events in their infants when they took 10 mg domperidone three times daily for two or four weeks during breastfeeding, regardless of whether they took the active drug or a placebo. A transgender woman took 50 mg spironolactone twice daily to suppress testosterone, 10 mg domperidone three times daily (later increased to 20 mg four times daily), 200 mg micronized progesterone orally daily, 8 mg estradiol orally daily, and pumped six times daily to induce lactation. After three months of treatment, the estradiol regimen was changed to a 0.025 mg patch daily, and the progesterone dose was reduced to 100 mg daily. Two weeks later, she began exclusively breastfeeding her partner's newborn. Exclusive breastfeeding continued for six weeks, during which the infant's growth, development, and bowel habits were normal. The patient continued partial breastfeeding for at least 6 months. A transgender woman was taking spironolactone 100 mg twice daily; progesterone 200 mg once daily; and estradiol 5 mg once daily. To increase milk production, she started taking domperidone 10 mg three times daily. After one month, she was able to express 3 to 5 ounces of milk daily. After 8 weeks, due to decreased milk production, the domperidone dose was increased to 30 mg three times daily. Her milk production returned to 3 to 5 ounces daily. By 6 months, although her serum prolactin levels remained elevated, her milk production decreased to approximately 5 ml per day. A transgender woman had been taking estradiol 2 mg twice daily for 14 years. 107 days before her partner's due date, she started taking domperidone 10 mg four times daily, and progesterone 100 mg daily. Simultaneously, the estradiol dose was increased to 4 mg twice daily. Ninety-four days before her due date, the dose of domperidone was increased to 20 mg four times daily; the dose of progesterone was increased to 200 mg daily; and the estrogen was changed to transdermal estradiol at 25 mcg daily. Thirty-four days before her due date, she discontinued progesterone. Starting 34 days before her due date, she began expressing and storing breast milk. By day 27 postpartum, she was able to breastfeed her baby twice daily, expressing 150 ml of breast milk daily, and was able to reduce the dose of domperidone to 20 mg three times daily. Lower doses reduce milk production.
◉ Effects on Lactation and Breast Milk
Domperidone increases serum prolactin levels in both lactating and non-lactating women. This effect is thought to be due to the drug's anti-dopaminergic effect. In non-pregnant women, domperidone was less effective than the same dose of oral metoclopramide in increasing serum prolactin levels; however, in multiparous women, the effects were similar. Domperidone has caused milk leakage in non-pregnant women and a male infant who was not breastfed. A paper published twice in two different journals reported two independent small studies. In the first study, 15 women with a history of lactation defects received 10 mg of domperidone orally three times daily from day 2 to day 5 postpartum (n = 8) or a placebo (n = 7). These patients were apparently not randomized, and blinding was not mentioned in the paper. No guidance or support on breastfeeding techniques was provided during the study. Serum prolactin levels were similar in all groups at the start of the study. From day 3 to day 5 postpartum, baseline serum prolactin levels were higher in the treatment group than in the placebo group. From day 2 postpartum, suckling-induced increases in serum prolactin were greater in the treatment group than in the placebo group. Milk production was calculated by measuring the infant's weight 24 hours before and after each feeding. From day 2 postpartum, the treatment group showed a greater increase in milk production; however, the lower average milk production in the placebo group was due to extremely low milk production in 3 women. The average weight gain of infants in the treatment group was also correspondingly higher. At one month postpartum, all mothers in the treatment group were breastfeeding well, but 5 out of 7 mothers in the untreated group experienced inadequate lactation (undefined). No correlation was found between baseline serum prolactin levels or elevated prolactin levels and milk production. In the same paper, researchers used the same methodology to study 17 primiparous women with inadequate lactation (below 30% of normal levels) two weeks postpartum. These women were randomly assigned to receive 10 mg of oral domperidone (n = 9) or a placebo (n = 8) three times daily for 10 days. At the start of the study, there was no significant difference in serum prolactin levels between the two groups. From day 2, serum prolactin levels in the treatment group were higher than in the control group; from day 4, milk production in the treatment group was also higher than in the control group. At the end of the study, milk production in all control group mothers did not increase from day 1. One month after the start of the study, milk production in all treatment group mothers reached normal levels. No correlation was found between serum prolactin levels and milk production. A well-designed but small-sample domperidone trial has also been published. In a randomized, double-blind trial, 20 women using a high-quality electric breast pump to express milk for preterm infants were randomly assigned to two groups, receiving domperidone 10 mg (n=11) or placebo (n=9) three times daily for 7 days. These mothers were on average 32 to 33 days postpartum. All mothers, despite receiving adequate guidance from lactation counselors, were still unable to produce sufficient breast milk for their infants. On day 5 of treatment, serum prolactin levels in the treatment group increased by 119 μg/L compared to the placebo group, while the placebo group only increased by 18 μg/L. Three days after discontinuation of treatment, serum prolactin levels in both groups returned to baseline levels. Although the baseline milk production in the domperidone group (partially estimated) was higher than that in the placebo group (48 ml daily), the mean daily milk production increased by 45% (to 184 ml) and 17% (to 66 ml) in the domperidone group and the placebo group, respectively, from day 2 to day 7. However, four women in the domperidone group failed to complete the study; only women who completed the study were included in the matching program, and their baseline profiles were similar. No follow-up was conducted after the 7-day study period to assess the lasting effect of domperidone on lactation success. While this study appears to provide evidence that domperidone is beneficial for increasing milk production in mothers of preterm infants who use breast pumps, several factors cast doubt on this conclusion: a 36% dropout rate in the active drug group, a lack of intention-to-treat analysis, and a significant difference in baseline milk production between the domperidone and placebo groups.
Twenty-five women took 20 mg of domperidone four times daily to increase milk production, but gradually reduced the dose over 2 to 4 weeks and eventually discontinued the medication. The duration of domperidone use was not specified in the abstract. All women had stable milk production, and their infants were all under 3 months old and growing normally. Of the 25 women, 23 did not increase formula feeding, and all infants grew normally, indicating that discontinuing domperidone did not adversely affect infant nutrition.
Six women who, despite consulting a lactation consultant, were still unable to provide sufficient breast milk for their premature infants received domperidone at either 10 mg three times daily or 20 mg three times daily, in a crossover pattern. Both doses increased baseline serum prolactin levels by similar amounts. Only four of the six women experienced an increase in milk production. The remaining four women experienced an increase in milk production from 8.7 g/h at baseline to 23.6 g/h at 30 mg/day and 29.4 g/h at 60 mg/day, but there was no statistically significant difference between the two doses. Mothers in the higher-dose group experienced side effects such as dry mouth, abdominal cramps, and headaches more frequently. During the introductory period, one mother withdrew from the study due to severe abdominal cramps. Additionally, constipation and low mood were reported in the higher-dose group. In a randomized, double-blind study, mothers of preterm infants (<31 weeks) with insufficient breast milk were randomized to receive domperidone 10 mg three times daily or a placebo. After 14 days, the increase in milk production in the domperidone group (+267%) was significantly greater than that in the placebo group (+19%). Breast milk calcium concentration increased in the domperidone group (+62%), while it decreased in the placebo group (-4%). Mothers taking domperidone showed a slight increase in breast milk carbohydrate concentration (+2.7%), while mothers taking a placebo showed a slight decrease (-2.7%). There were no statistically significant differences in protein, energy, fat, sodium, or phosphate concentrations between the two groups.
A retrospective, non-controlled case series reported on 14 mothers of preterm infants treated in the intensive care unit with domperidone 20 mg three times daily to increase breast milk production. Within 14 days, breast milk output increased by 48%. However, the report was difficult to interpret due to the lack of a control group.
Mothers who underwent full-term cesarean section were randomly assigned to two groups, receiving domperidone 10 mg orally (n = 22) or a placebo (n = 23) four times daily in a double-blind manner, starting within 24 hours postpartum. Nurses collected breast milk from the mothers using an electric breast pump for 15 minutes each time, twice daily, two hours after the mothers began breastfeeding. At all time points, including baseline, the domperidone group collected more milk using this incomplete collection method than the placebo group. Seven women in the domperidone group reported dry mouth, while none in the placebo group did. These results are not clinically significant due to endpoint selection and baseline imbalance. Mothers (mean gestational age 28 weeks) who were expressing milk for their infants in the neonatal intensive care unit (NICU) received instructions on methods to increase breast milk production. If their daily milk production was less than 160 ml per kilogram of infant body weight after several days, mothers were randomly assigned to either the domperidone or metoclopramide group, receiving 10 mg orally three times daily for 10 days in a double-blind manner. 31 mothers receiving domperidone and 34 mothers receiving metoclopramide provided daily milk production data over 10 days. Over 10 days, milk production increased by 96% in the domperidone group and by 94% in the metoclopramide group; there was no statistically significant difference between the two groups. Some mothers continued to measure milk production after the end of treatment. The results were similar in both groups. Side effects in the domperidone group (3 women) included headache, diarrhea, mood swings, and dizziness. Side effects in the metoclopramide group (7 women) included headache (3 women), diarrhea, mood swings, changes in appetite, dry mouth, and breast discomfort. The lack of a placebo group and missing data for some mothers necessitated filling the gaps by predicting milk volume, which weakened the reliability of the results. A double-blind, controlled trial compared the effects of two doses of domperidone on increasing milk production in mothers of preterm infants. Mothers received either 10 mg (n=8) or 20 mg (n=7) three times daily for 4 weeks, followed by a gradual tapering over the next 2 weeks. Both doses increased milk production, but the difference in milk production between the two groups was not statistically significant. A randomized trial in Pakistan compared the effects of 10 mg domperidone versus placebo three times daily on women who delivered at term and whose single milk output from each breast was ≤10 ml on day 6 postpartum. All women received proper breastfeeding technique instruction. Seven days after administration of either the medication or placebo, women were assigned to either a single milk output ≥50 ml or <50 ml group based on the single milk output. Serum prolactin levels were not measured in this trial. In the domperidone group, 72% of women successfully increased their milk production, compared to only 11% in the placebo group. Problems with this study included a significant lack of blinding between the drug, researchers, and mothers, and the endpoint being questionable: the amount of milk expressed at a single, uncontrolled time point, rather than total daily milk production. A retrospective study compared hospitalized mothers of preterm infants who received domperidone (n = 45) with mothers who did not receive the drug due to cost (n = 50). Following standard treatment, treated mothers saw their daily milk production increase from 125 ml to 415 ml after 30 days of treatment. Untreated mothers experienced a decrease in daily milk production from 158 ml to 88 ml after 30 days. A randomized trial in India involving 32 mothers with insufficient milk production and infants in the neonatal intensive care unit treated with domperidone (dosage not specified) for 7 to 14 days found that after 7 days of treatment, the domperidone group had a greater increase in milk production (186 ml) than the placebo group (70 ml). There was no difference in serum prolactin levels between the domperidone and placebo groups on days 1 and 8 of treatment. There was also no difference in infant weight gain between the two groups. A randomized trial in Indonesia involving 50 mothers of preterm infants with insufficient milk production after 7 days of breastfeeding instruction treated with domperidone 10 mg three times daily for 10 days found that after 7 days of treatment, the domperidone group had a greater increase in milk production (182 ml) than the placebo group (72 ml). Milk production continued to increase three days after discontinuation of treatment, on day 10. A randomized, double-blind study conducted at a hospital in Thailand randomly assigned 25 mothers who had given birth vaginally at term to two groups: one group received a placebo (n = 25) and the other received domperidone 10 mg three times daily (n = 25) for 4 days. All mothers began treatment 24 hours postpartum. Results showed that at 48 hours postpartum (3 ml in the placebo group, 8 ml in the domperidone group), 72 hours postpartum (10 ml in the placebo group, 15 ml in the domperidone group), and 96 hours postpartum (15 ml in the placebo group, 35 ml in the domperidone group), the amount of milk produced per manual expression was significantly higher in the placebo group than in the placebo group. No follow-up was conducted on breast milk supply or infant outcomes. In a double-blind, multicenter study, mothers of preterm infants received either domperidone 10 mg three times daily for 28 days or a placebo three times daily for 14 days, followed by domperidone 10 mg three times daily for another 14 days. Only mothers with documented low milk production were included, and all mothers received breastfeeding support. Within the first two weeks, 78% of mothers receiving domperidone experienced a 50% increase in milk production, compared to 58% of mothers receiving a placebo (odds ratio 2.56). After four weeks, the proportions were 69% and 62% in the two groups, respectively, but the difference was not statistically significant. At six weeks postpartum, there were no significant differences between the two groups in terms of breastfeeding or formula supplementation. The authors concluded that domperidone helps more mothers increase milk production within 8 to 21 days postpartum; however, the increase in milk production was limited. In a secondary analysis of the results, the authors found no difference in response between mothers of infants born at 23 to 26 weeks of gestation and mothers of infants born at 27 to 29 weeks of gestation. Further secondary analyses of the data showed no difference in results regardless of whether domperidone was started at 8 to 14 days or 15 to 21 days postpartum. Mothers with an initial milk production of 200 ml/day or less experienced the highest percentage increase in milk production, but mothers with an initial milk production of 100 ml/day or less had a persistently low absolute milk production. This retrospective study analyzed women who had given birth to preterm infants at 30 weeks of gestation or less. Overall, mothers who received domperidone lactation stimulant treatment during their postpartum hospital stay (n = 84) were not more likely to breastfeed their infants at discharge than mothers who did not receive domperidone treatment (n = 114). However, in mothers weighing 70 kg or more, domperidone use was associated with a decreased likelihood of breastfeeding at discharge. A meta-analysis of studies on domperidone as a lactation stimulant for mothers of preterm infants included 5 studies with 95 mothers randomly assigned to the domperidone group and 97 mothers randomly assigned to the placebo group. All studies used a dose of 10 mg three times daily for 5 to 14 days. The results showed that domperidone use increased average daily milk production by 88 ml, with a 95% confidence interval of 57 to 120 ml. A meta-analysis of studies on domperidone as a lactation stimulant for breastfeeding mothers included 5 studies, with 120 mothers randomly assigned to the domperidone group and 125 mothers randomly assigned to the placebo group. Three of these studies (73 mothers randomly assigned to the domperidone group and 77 mothers randomly assigned to the placebo group) had been included in a previously published meta-analysis. Four studies used a dose of 10 mg/day for 7 to 14 days, and one study used a dose of 10 mg/day for 4 days. The results showed that domperidone use increased average daily milk production by 94 ml, with a 95% confidence interval of 71 to 117 ml. A subgroup analysis found that using domperidone for more than 7 days did not additionally increase milk production. A study of 10 mothers of premature infants conducted in the neonatal intensive care unit involved mothers who, two weeks postpartum, received 10 mg domperidone three times daily if their milk production was less than 300 ml or less than 160 ml/kg of their infant's weight. Initially, the median daily milk production was 60 ml (range 2–310 ml), increasing to 176 ml (range 11–400 ml) by day 14. Seven of the ten mothers experienced an increase in milk production of 1.5 times or more from the initial value. Before medication, the median serum prolactin concentration was 46 μg/L (range 4–128 μg/L), increasing to 167 μg/L (range 59–356 μg/L) by day 14. No correlation was found between serum prolactin levels and milk production; the three mothers with elevated prolactin levels did not experience increased milk production. A randomized study included mothers of infants who were mixed-fed in the first month postpartum (20 mothers in each group), comparing the effects of receiving 12 sessions of breast electroacupuncture or low-intensity laser therapy over one month with a control group. All mothers also received oral domperidone 10 mg three times daily. Results showed that both laser therapy and electroacupuncture were more effective than domperidone alone in increasing serum prolactin levels, increasing infant weight, and improving mothers' perception of milk production. A randomized, double-blind trial compared the efficacy of domperidone versus placebo in mothers with insufficient milk production and neonatal illness. Of the 166 eligible mothers, 72% experienced increased milk production without medication after counseling. Ultimately, 24 mothers received domperidone 20 mg three times daily for 14 days, and 23 mothers received a placebo. After 7 days of treatment, prolactin levels increased from 72.85 mcg/L to 223.4 mcg/L in the domperidone group and from 42.33 mcg/L to 60.08 mcg/L in the placebo group. Daily milk production increased from 156 mL to 401 mL in the domperidone group and from 176 mL to 261 mL in the placebo group. 95% of infants in the domperidone group were still breastfeeding at discharge, compared to only 52% in the placebo group. All differences between groups were statistically significant. A woman with complete androgen insensitivity syndrome became a mother through surrogacy. To be able to breastfeed, she began treatment 4 weeks before delivery, including the use of topical estrogen patches, oral 20 mg domperidone three times daily, and mechanical breast stimulation. After delivery, the estrogen patches were discontinued. The patient was able to partially breastfeed her infant for one month. In an Australian survey of breastfeeding mothers, 355 mothers took domperidone as a lactation stimulant. On average, mothers rated the efficacy of domperidone slightly above "moderately effective" on the Likert scale. 45% of mothers taking domperidone reported adverse reactions, the most common being weight gain, headache, dry mouth, and fatigue. 9% of women discontinued the medication due to side effects. Mothers who underwent a lower segment cesarean section at or near term and felt they had insufficient milk production were randomly assigned to receive either domperidone 10 mg (n = 183) or a placebo (n = 183), three times daily for 3 days. All participants watched a 5-minute video about the benefits of breastfeeding. Protocol analysis revealed that the domperidone group had a higher rate of exclusive breastfeeding at 7 days postpartum than the placebo group (96% vs 86%). The domperidone group had numerically higher rates of exclusive breastfeeding at 3 and 6 months postpartum than the placebo group, but the differences were not statistically significant. There was no difference in weight gain between the two groups of infants at 6, 10, 14, and 9 months postpartum. A transgender woman was expressing milk and partially breastfeeding her partner's infant. 24-hour mixed milk samples were analyzed monthly starting 56 days before delivery. The participant's milk contained protein, fat, lactose, and calories at or above the levels of full-term breast milk. A transgender woman was receiving gender affirmation therapy. She was taking 4 mg of estradiol sublingually twice daily, 100 mg of spironolactone sublingually twice daily, and 200 mg of progesterone at bedtime. To prepare for her partner's pregnancy, her estradiol dosage was increased to 6 mg sublingually twice daily; her progesterone dosage was increased to 400 mg at bedtime. She also started taking domperidone at 10 mg sublingually twice daily to increase serum prolactin levels, later increasing to 20 mg sublingually four times daily. Before delivery, progesterone was discontinued, spironolactone was reduced to 100 mg daily, and estradiol was switched to transdermal administration at 25 mcg daily. On day 59 postpartum, estradiol was switched to sublingual administration at 2 mg daily, and spironolactone was increased to 100 mg twice daily. This patient produced up to 240 ml of breast milk daily, containing typical macronutrient and oligosaccharide levels. A randomized study of women who delivered singletons vaginally compared the effects of domperidone 10 mg, the Thai herbal product Plook-Fire-Thatu, and a placebo, each administered three times daily starting from day one postpartum. Plook-Fire-Thatu contains various herbs from the Piper genus, with piperine likely being its active ingredient. Piperine can also enhance the bioavailability of certain chemicals. The formula also includes ginger, which is said to have galactagogue properties. Researchers assessed milk production by measuring infant weight three times daily. On the third day of treatment, the herbal product group showed a more significant increase in milk production compared to the placebo or domperidone group, but there was no difference in infant weight between the groups. The mothers in the herbal product group had higher body temperatures, consistent with the traditional Chinese medicine theory of "increasing heat to promote lactation." A transgender woman wishing to breastfeed received daily treatment with 150 mcg of estradiol transdermal patches and 100 mg of progesterone orally. Subsequently, she added daily 100 mcg of estradiol spray and 10 mg of domperidone four times daily. The domperidone dose was then doubled to 20 mg four times daily, and the progesterone dose was doubled to 100 mg twice daily. After further adjustments to the estradiol and progesterone dosages, 7 ml of milk was expressed using a breast pump, but lactation was discontinued at the patient's request two weeks after the i

[1]. J Agric Food Chem . 2011 Sep 14;59(17):9691-9

[2]. Bull Exp Biol Med . 2013 Oct;155(6):705-7.

[3]. Am J Vet Res . 2010 Mar;71(3):281-7.

[4]. J Anim Sci . 2003 Oct;81(10):2568-74.

[5]. Am J Vet Res . 1994 May;55(5):722-9.

[6]. Am J Vet Res . 2013 Aug;74(8):1103-10.

Domperidone's chemical name is 1-[3-(piperidin-1-yl)propyl]-1,3-dihydro-2H-benzimidazole-2-one, wherein the 4-position of the piperidine ring is replaced by a 5-chloro-1,3-dihydro-2H-benzimidazole-2-one-1-yl group. It is a dopamine antagonist used for short-term treatment of nausea and vomiting, and to control gastrointestinal side effects of dopaminergic drugs in the treatment of Parkinson's disease. The free base is used in oral suspensions, while the maleate is used in tablets. It has antiemetic and dopamine antagonistic effects. It belongs to the benzimidazole class and the heteroarylpiperidine class of compounds. It is a specific blocker of dopamine receptors. It accelerates gastrointestinal motility, promotes prolactin release, and is used as an antiemetic and a tool for studying dopaminergic mechanisms. Domperidone is a peripherally specific dopamine receptor D2 (D2R) antagonist with antiemetic, gastrointestinal motility, and galactagogue effects. After administration, domperidone binds to D2Rs expressed by peripheral neurons; this inhibits dopamine binding and D2R-mediated signaling. Inhibition of peripheral D2R signaling can prevent or alleviate various gastrointestinal symptoms, such as nausea and vomiting, and may help relieve symptoms of reflux and various other upper gastrointestinal disorders.
A dopamine receptor-specific blocker. It accelerates gastrointestinal motility, promotes prolactin release, and can be used as an antiemetic and a tool in the study of dopaminergic mechanisms.
See also: Domperidone maleate (its active ingredient)...see more...

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Drug Indications>
For the treatment of indigestion, heartburn, upper abdominal pain, nausea, and vomiting.

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Mechanism of Action>
Domperidone is an adjuvant for gastrointestinal emptying (delay) and a peristaltic stimulant. The gastric motility properties of domperidone are related to its peripheral dopamine receptor blocking properties. Domperidone promotes gastric emptying and shortens small intestinal transit time by enhancing esophageal and gastric motility and reducing lower esophageal sphincter pressure. Antiemetic effect: The antiemetic effect of domperidone is related to its dopamine receptor blocking activity at the chemoreceptor trigger zone and gastric level. It has a strong affinity for D2 and D3 dopamine receptors located in the chemoreceptor trigger zone (outside the blood-brain barrier), which regulates physiological processes such as nausea and vomiting. Domperidone (R33812) is a peripheral dopamine D2/D3/D4 receptor antagonist with prokinetic, antiemetic, and lactogenic effects [2,3,4,5,6]. Mechanism of action: Blocking peripheral D2 receptors in the gastrointestinal tract (enhancing gastric motility and accelerating gastric emptying); inhibiting D2 receptors in the chemoreceptor trigger zone (antiemetic); antagonizing pituitary D2 receptors (promoting prolactin release) [4,5,6].
- Indications (human): Nausea and vomiting (chemotherapy-induced, postoperative, diabetic gastroparesis); gastrointestinal motility disorders [6].
- Indications (veterinary): Inadequate milk production in dairy cows; gastrointestinal stasis in dogs/cats; diarrhea in weaned piglets (adjunctive therapy) [3,4,6].
- Routes of administration: Humans: Oral (10 mg, three times daily); Veterinary: Dogs (0.5–2 mg/kg, orally daily), dairy cows (30 mg, subcutaneously daily) [3,6].
- FDA warnings: Avoid use in patients with prolonged QT intervals or heart failure; use with caution when using CYP3A4 inhibitors [6].
- Clinical advantages: Peripheral selectivity (low central nervous system penetration) minimizes extrapyramidal side effects [6].

C22H24CLN5O2

425.91

425.161

C, 62.04; H, 5.68; Cl, 8.32; N, 16.44; O, 7.51

57808-66-9

Domperidone monomaleate; 83898-65-1; Domperidone-d6; 1329614-18-7

3151

Solid powder

1.5±0.1 g/cm3

723.6±70.0 °C at 760 mmHg

242.5ºC

391.4±35.7 °C

0.0±2.4 mmHg at 25°C

1.729

4.63

2

3

5

30

655

0

ClC1C([H])=C([H])C2=C(C=1[H])N([H])C(N2C1([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])N2C(N([H])C3=C([H])C([H])=C([H])C([H])=C23)=O)C([H])([H])C1([H])[H])=O

FGXWKSZFVQUSTL-UHFFFAOYSA-N

InChI=1S/C22H24ClN5O2/c23-15-6-7-20-18(14-15)25-22(30)28(20)16-8-12-26(13-9-16)10-3-11-27-19-5-2-1-4-17(19)24-21(27)29/h1-2,4-7,14,16H,3,8-13H2,(H,24,29)(H,25,30)

6-chloro-3-[1-[3-(2-oxo-3H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1H-benzimidazol-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.75 mg/mL (6.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.75 mg/mL (6.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.75 mg/mL (6.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)