Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H24ClN5O2.C4H4O4 |
Molecular Weight | 541.983 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.ClC1=CC2=C(C=C1)N(C3CCN(CCCN4C(=O)NC5=C4C=CC=C5)CC3)C(=O)N2
InChI
InChIKey=OAUUYDZHCOULIO-BTJKTKAUSA-N
InChI=1S/C22H24ClN5O2.C4H4O4/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;5-3(6)1-2-4(7)8/h1-2,4-7,14,16H,3,8-13H2,(H,24,29)(H,25,30);1-2H,(H,5,6)(H,7,8)/b;2-1-
Molecular Formula | C22H24ClN5O2 |
Molecular Weight | 425.911 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C4H4O4 |
Molecular Weight | 116.0722 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/17488253Curator's Comment: description was created based on several sources, including
https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm368736.htm
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17488253
Curator's Comment: description was created based on several sources, including
https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm368736.htm
Domperidone is a peripherally selective D2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Domperidone was not approved in USA due to risks of cardiac arrhythmias, cardiac arrest, and sudden death, but is available in other countries. However, FDA allows access to Domperidone through an expanded access investigational new drug application (IND) to patients with gastroesophageal reflux disease with upper GI symptoms, gastroparesis, and chronic constipation. As an “off-label” use, domperidone is prescribed to breastfeeding women to enhance their milk production.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568818 |
1.0 nM [Ki] | ||
Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14521403 |
3.5 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | MOTILIUM Approved UseMOTILIUM is indicated for the short-term treatment in adults of symptoms associated with idiopathic or diabetic gastroparesis (once control of diabetes has been established by diet and/or insulin, an attempt should be made to discontinue MOTILIUM). |
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Primary | MOTILIUM Approved UseMOTILIUM is indicated for the short-term treatment in adults of intractable nausea and vomiting from any cause. |
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Primary | MOTILIUM Approved UseDomperidone is not officially approved to treat gastroesophageal reflux disease, but FDA recognizes that there are some patients with severe gastrointestinal motility disorders that are difficult to manage with available therapy for whom domperidone’s potential benefits may justify its potential risks. Patients 12 years of age and older with certain gastrointestinal (GI) conditions who have failed standard therapies may be able to receive treatment with domperidone through an expanded access investigational new drug application (IND). These conditions include gastroesophageal reflux disease with upper GI symptoms, gastroparesis, and chronic constipation. |
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Primary | MOTILIUM Approved UseDomperidone is not officially approved to treat gastroesophageal reflux disease, but FDA recognizes that there are some patients with severe gastrointestinal motility disorders that are difficult to manage with available therapy for whom domperidone’s potential benefits may justify its potential risks. Patients 12 years of age and older with certain gastrointestinal (GI) conditions who have failed standard therapies may be able to receive treatment with domperidone through an expanded access investigational new drug application (IND). These conditions include gastroesophageal reflux disease with upper GI symptoms, gastroparesis, and chronic constipation. |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
17.67 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17598698/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
87.08 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17598698/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
327 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
289 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
10 mg single, intramuscular dose: 10 mg route of administration: Intramuscular experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
57.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
259 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
243 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
60 mg single, rectal dose: 60 mg route of administration: Rectal experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
463 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
249 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
13.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17598698/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
7.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7250152/ |
DOMPERIDONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Disc. AE: CNS disorder (NOS)... AEs leading to discontinuation/dose reduction: CNS disorder (NOS) (2%) Sources: |
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Disc. AE: Facial swelling, Abdominal pain... AEs leading to discontinuation/dose reduction: Facial swelling (3.2%) Sources: Abdominal pain (3.2%) Abdominal distension (3.2%) Galactorrhoea (3.2%) Mastalgia (6.4%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
CNS disorder (NOS) | 2% Disc. AE |
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Abdominal distension | 3.2% Disc. AE |
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Abdominal pain | 3.2% Disc. AE |
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Facial swelling | 3.2% Disc. AE |
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Galactorrhoea | 3.2% Disc. AE |
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Mastalgia | 6.4% Disc. AE |
20 mg 4 times / day multiple, oral Recommended Dose: 20 mg, 4 times / day Route: oral Route: multiple Dose: 20 mg, 4 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
inconclusive [IC50 15.8489 uM] | ||||
inconclusive [IC50 6.3096 uM] | ||||
no [IC50 >10 uM] | ||||
no [IC50 >10 uM] | ||||
no [IC50 >10 uM] | ||||
no [IC50 >10 uM] | ||||
no [IC50 >133 uM] | ||||
no [IC50 >133 uM] | ||||
no [IC50 >133 uM] | ||||
no [IC50 >133 uM] | ||||
yes [EC50 106 uM] | ||||
yes [IC50 14.8 uM] | ||||
yes [IC50 2.3 uM] | ||||
yes [IC50 3.1623 uM] | ||||
yes [IC50 7.9 uM] | ||||
yes [Inhibition 10 uM] | ||||
yes [Inhibition 10 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | ||||
likely | ||||
weak | ||||
weak | ||||
weak | ||||
weak | ||||
weak | ||||
weak | ||||
yes | ||||
yes | ||||
yes | yes (co-administration study) Comment: Itraconazole increased Cmax by 2.7-fold and AUCinf by 3.2-fold |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Age-dependent effect of domperidone on dopamine release by the hypoxic carotid body in the rabbit. | 2001 |
|
Excitation of rat striatal large neurons by dopamine and/or glutamate released from nerve terminals via presynaptic nicotinic receptor (A4beta2 type) stimulation. | 2001 Aug |
|
Effects of dopaminergic drugs on inflammatory bowel disease induced with 2,4-dinitrofluorbenzene in BALB/c mice. | 2001 Aug |
|
[Evidence-based therapy of systemic sclerosis]. | 2001 Dec |
|
Effect of adrenalectomy and dexamethasone treatment on prolactin secretion of lactating rats. | 2001 Dec |
|
Gastroparesis: prevalence, clinical significance and treatment. | 2001 Dec |
|
Effects of gastrointestinal stimulant and suppressant pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic. | 2001 Nov |
|
Heart rate response to hypoxic exercise: role of dopamine D2-receptors and effect of oxygen supplementation. | 2001 Oct |
|
Pharmacological characterization of cyclosporine A-induced kaolin intake in rats. | 2001 Oct-Nov |
|
Treatment of non-ulcer dyspepsia: a meta-analysis of placebo-controlled prospective studies. | 2001 Sep |
|
Dopamine D(2) receptor activation causes mitogenesis via p44/42 mitogen-activated protein kinase in opossum kidney cells. | 2001 Sep |
|
Occurrence of dopaminergic (D(2)) receptors within the rabbit pulmonary circulation. | 2002 |
|
Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women. | 2002 |
|
Galactogogues: medications that induce lactation. | 2002 Aug |
|
Simultaneous determination of domperidone maleate and cinnarizine in a binary mixture using derivative ratio spectrophotometry and classical least squares calibration. | 2002 Aug 22 |
|
Blockade of spinal dopamine D2 receptors enhances the pressor effect of intravenous quinpirole in normotensive, conscious rats. | 2002 Feb |
|
[Prokinetics of gastrointestinal system; its newer aspects with regard to motillity stimulants]. | 2002 Feb |
|
Opioid mediated anti-nociceptive effect of domperidone and cisapride in mice. | 2002 Jan |
|
Dopaminergic modulation of ventilation in obese Zucker rats. | 2002 Jan |
|
KDR-5169, a new gastrointestinal prokinetic agent, enhances gastric contractile and emptying activities in dogs and rats. | 2002 Jan 11 |
|
Synthesis and structure-activity relationships of 4-amino-5-chloro-N-(1,4-dialkylhexahydro-1,4-diazepin-6-yl)-2-methoxybenzamide derivatives, novel and potent serotonin 5-HT3 and dopamine D2 receptors dual antagonist. | 2002 Jul |
|
D2 -like receptor stimulation decreases effective renal plasma flow and glomerular filtration rate in spontaneously hypertensive rats. | 2002 Jul |
|
Quantitative and qualitative assessment of milk production after pharmaceutical induction of lactation in the mare. | 2002 Jul-Aug |
|
[Digestive manifestations in systemic sclerosis]. | 2002 Jun |
|
Pharmacology and toxicity of nicotinamide combined with domperidone during fractionated radiotherapy. | 2002 Jun |
|
Gastric emptying in diabetes: clinical significance and treatment. | 2002 Mar |
|
Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats. | 2002 Mar |
|
Ranitidine alone and in combination with domperidone in reflux-type dyspepsia. | 2002 Mar-Apr |
|
Distribution of domperidone into the rat brain is increased by brain ischaemia or treatment with the P-glycoprotein inhibitor verapamil. | 2002 May |
|
A dose-finding study of carboplatin-epirubicin-docetaxel in advanced epithelial ovarian cancer. | 2002 May 6 |
|
Age-related changes in dopamine D2 receptors in rat heart and coronary vessels. | 2002 May-Jun |
|
Severe ventricular arrhythmia and sudden death on neuroleptics. | 2002 Oct |
|
Calcitonin gene-related peptide and adrenomedullin release in humans: effects of exercise and hypoxia. | 2002 Oct 15 |
|
Dynamic modelling of a challenge-escalation cross-over study of treatment of capsaicin-induced coughing. | 2002 Oct 30 |
|
Blunted central bromocriptine-induced tachycardia in conscious, malnourished rats. | 2003 Apr |
|
Bowel cleansing for diagnostic colonoscopy: which method is preferable? Istanbul experience. | 2003 Apr |
|
Activation of dopamine D2-like receptors attenuates pulmonary C-fiber hypersensitivity in rats. | 2003 Apr 15 |
|
Tumoral versus non-tumoral hyperprolactinemia in children and adolescents: possible usefulness of the domperidone test. | 2003 Feb |
|
Dopamine-induced protection against indomethacin-evoked intestinal lesions in rats--role of anti-intestinal motility mediated by D2 receptors. | 2003 Feb |
|
Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease. | 2003 Feb |
|
Simultaneous determination of domperidone and cinnarizine in a binary mixture using derivative spectrophotometry, partial least squares and principle component regression calibration. | 2003 Jan |
|
Area postrema mediates gastric motor response induced by apomorphine in rats. | 2003 Jan 17 |
|
Neuroprotective effect of nitric oxide against NMDA-induced neurotoxicity in the rat retina is associated with tyrosine hydroxylase expression. | 2003 Jul 4 |
|
Determination of ambroxol in human plasma using LC-MS/MS. | 2003 Jun 1 |
|
Olfactory sensitivity to catecholamines and their metabolites in the goldfish. | 2003 Mar |
|
Spectrophotometric methods for the determination of anti-emetic drugs in bulk and in pharmaceutical preparations. | 2003 May |
|
Studies on the interactions between drug and estrogen. II. On the inhibitory effect of 29 drugs reported to induce gynecomastia on the oxidation of estradiol at C-2 or C-17. | 2003 May |
|
Effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease. | 2003 May |
|
Effects of gonadotropin-releasing hormone agonist and dopamine antagonist on hypothalamus-pituitary-gonadal axis of pre-pubertal female red seabream (Pagrus major). | 2003 May |
|
Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion. | 2003 May |
Patents
Sample Use Guides
Domperidone should be taken 15-30 minutes before meals and, if necessary, before retiring. Adult dose of the drug is 10 mg three times daily. Domperidone is also available as suppository or as a solution for intramuscular injection.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568818
After dissection, rat striata were homogenized by seven manual strokes in a Wheaton Teflon-glass homogenizer with ice cold 50 mM HEPES buffer, centrifuged at 27000g, the supernatant was discarded. The pellet was homogenized (five strokes), resuspended in ice cold buffer, and centrifuged again. Nonspecific binding of [3H]Spiperone (ca.0.07 nM) was defined by adding unlabeled chlorpromazine. Binding was terminated by filtering with 15 mL of ice cold buffer. Radioactivity was determined on an LKB-1219 Rack-Beta liquid scintillation counter. Domperidone binds to D2 receptorss with Ki of 1 nM
Substance Class |
Chemical
Created
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Record UNII |
899U5WF46A
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Record Status |
Validated (UNII)
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Record Version |
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DBSALT002902
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236099
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DTXSID901019221
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899U5WF46A
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100000087542
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6604595
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SUB01815MIG
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83898-65-1
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281-277-7
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99497-03-7
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NON-SPECIFIC STOICHIOMETRY |
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PARENT -> SALT/SOLVATE | |||
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PARENT -> SALT/SOLVATE |
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IMPURITY -> PARENT | |||
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IMPURITY -> PARENT | |||
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IMPURITY -> PARENT | |||
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IMPURITY -> PARENT | |||
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IMPURITY -> PARENT |
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ACTIVE MOIETY |