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=CC=C2N(C3CCN(CCCN4C(=O)NC5=C4C=CC=C5)CC3)C(=O)NC2=C1
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 | C4H4O4 |
| Molecular Weight | 116.0722 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
| 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 |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm368736.htm
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
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL217 |
1.0 nM [Ki] | ||
Target ID: CHEMBL234 |
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). |
|||
| Primary | MOTILIUM Approved UseMOTILIUM is indicated for the short-term treatment in adults of intractable nausea and vomiting from any cause. |
|||
| 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. |
|||
| 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. |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Anti-emetics. | 2001 |
|
| 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 |
|
| [Study on relationship between the reflux laryngitis and gastroesophageal reflux disease]. | 2001 Dec |
|
| [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 |
|
| Gastroparesis and its management. | 2001 Jul-Sep |
|
| Stimulation of dopamine receptors inhibited Ca2+-calmodulin-dependent protein kinase II activity in rat striatal slices. | 2001 Nov |
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| 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 |
|
| [A case of the successful treatment of the esophageal leukoplakia with rabeprazole]. | 2002 |
|
| 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 |
|
| Role of tyrosine kinase and p44/42 MAPK in D(2)-like receptor-mediated stimulation of Na(+), K(+)-ATPase in kidney. | 2002 Apr |
|
| Simultaneous determination of domperidone maleate and cinnarizine in a binary mixture using derivative ratio spectrophotometry and classical least squares calibration. | 2002 Aug 22 |
|
| Acitretin-associated thrombotic stroke. | 2002 Dec |
|
| 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 |
|
| New insight into the functional role of acetylcholine in developing embryonic rat retinal neurons. | 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 |
|
| Pro-erectile effect of systemic apomorphine: existence of a spinal site of action. | 2002 Jan |
|
| KDR-5169, a new gastrointestinal prokinetic agent, enhances gastric contractile and emptying activities in dogs and rats. | 2002 Jan 11 |
|
| 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 |
|
| Determination of domperidone in human plasma by LC-MS and its pharmacokinetics in healthy Chinese volunteers. | 2002 Mar |
|
| Gastric emptying in diabetes: clinical significance and treatment. | 2002 Mar |
|
| Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats. | 2002 Mar |
|
| Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantitation of domperidone in human plasma. | 2002 Mar 8 |
|
| 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 |
|
| Domperidone is more effective than cisapride in children with diabetic gastroparesis. | 2002 May |
|
| A dose-finding study of carboplatin-epirubicin-docetaxel in advanced epithelial ovarian cancer. | 2002 May 6 |
|
| Protective effect of dopamine D2 agonists in cortical neurons via the phosphatidylinositol 3 kinase cascade. | 2002 Nov 1 |
|
| Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. | 2002 Nov 4 |
|
| Severe ventricular arrhythmia and sudden death on neuroleptics. | 2002 Oct |
|
| Dynamic modelling of a challenge-escalation cross-over study of treatment of capsaicin-induced coughing. | 2002 Oct 30 |
|
| Bowel cleansing for diagnostic colonoscopy: which method is preferable? Istanbul experience. | 2003 Apr |
|
| Relative efficacy of some prokinetic drugs in morphine-induced gastrointestinal transit delay in mice. | 2003 Apr |
|
| Potentiation of domperidone-induced catalepsy by a P-glycoprotein inhibitor, cyclosporin A. | 2003 Apr |
|
| Activation of dopamine D2-like receptors attenuates pulmonary C-fiber hypersensitivity in rats. | 2003 Apr 15 |
|
| Simultaneous determination of domperidone and cinnarizine in a binary mixture using derivative spectrophotometry, partial least squares and principle component regression calibration. | 2003 Jan |
|
| Substrate-dependent regulation of MAO-A in rat mesangial cells: involvement of dopamine D2-like receptors. | 2003 Jan |
|
| Neuroprotective effect of nitric oxide against NMDA-induced neurotoxicity in the rat retina is associated with tyrosine hydroxylase expression. | 2003 Jul 4 |
|
| Effects of gonadotropin-releasing hormone agonist and dopamine antagonist on hypothalamus-pituitary-gonadal axis of pre-pubertal female red seabream (Pagrus major). | 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
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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admin
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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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