DOMPERIDONE MALEATE

Possibly Marketed Outside US

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

Structure Search

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-

HIDE SMILES / InChI

Description
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
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568818	Antagonist 2849		1.0 nM [Ki]
Dopamine D3 receptor 97 Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14521403	Antagonist 2849		3.5 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Gastroparesis 9 Sources: http://www.janssen.com/australia/sites/www_janssen_com_australia/files/prod_files/live/motilium_pi.pdf	Primary	Approved 8583	MOTILIUM Approved Use MOTILIUM 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).
Emesis 3 Sources: http://www.janssen.com/australia/sites/www_janssen_com_australia/files/prod_files/live/motilium_pi.pdf	Primary	Approved 8583	MOTILIUM Approved Use MOTILIUM is indicated for the short-term treatment in adults of intractable nausea and vomiting from any cause.
Gastroesophageal reflux disease 68 Sources: https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm368736.htm	Primary	Phase IV 63	MOTILIUM Approved Use Domperidone 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.
Chronic constipation 7 Sources: https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm368736.htm	Primary	Not Provided 511	MOTILIUM Approved Use Domperidone 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.

C_max

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	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

T_1/2

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

F_unbound

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: https://pubmed.ncbi.nlm.nih.gov/10235199/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/10235199/	Disc. AE: CNS disorder (NOS)... AEs leading to discontinuation/dose reduction: CNS disorder (NOS) (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/10235199/
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: https://pubmed.ncbi.nlm.nih.gov/6357963/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/6357963/	Disc. AE: Facial swelling, Abdominal pain... AEs leading to discontinuation/dose reduction: Facial swelling (3.2%) Abdominal pain (3.2%) Abdominal distension (3.2%) Galactorrhoea (3.2%) Mastalgia (6.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/6357963/

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: https://pubmed.ncbi.nlm.nih.gov/10235199/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/10235199/
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: https://pubmed.ncbi.nlm.nih.gov/6357963/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/6357963/
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: https://pubmed.ncbi.nlm.nih.gov/6357963/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/6357963/
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: https://pubmed.ncbi.nlm.nih.gov/6357963/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/6357963/
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: https://pubmed.ncbi.nlm.nih.gov/6357963/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/6357963/
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: https://pubmed.ncbi.nlm.nih.gov/6357963/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/6357963/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 879 CYP2E1 1060 CYP1A2 2153 CYP2C19 2057 MRP3 246 MRP4 290 MRP2 499 OATP1B1 1079 BSEP 550 OCT2 779 MATE1 415 MATE2K 17 OATP1B3 961 Nav1.5 116 P-gp 1741	CYP2B6 776 CYP2C8 810 CYP1A2 1197 CYP2C19 1119 P-gp 2052 CYP2A6 626 CYP2E1 729 CYP3A5 446

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjE5OTE2In19 \| https://pubmed.ncbi.nlm.nih.gov/20082577/	inconclusive [IC50 15.8489 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	inconclusive [IC50 6.3096 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >10 uM]
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1NzQ4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1OTE4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	no [IC50 >133 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11113639/	yes [EC50 106 uM]
MATE2K 17	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	yes [IC50 14.8 uM]
MATE1 416	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	yes [IC50 2.3 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjE5OTE2In19	yes [IC50 3.1623 uM]
OCT2 782	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	yes [IC50 7.9 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15327587/	likely
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15327587/	likely
CYP1A2 1197	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	weak
CYP2B6 776	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0NzI5IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	weak
CYP2C19 1119	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	weak
CYP2C8 810	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNzIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	weak
CYP2C9 1193	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	weak
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15327587/	weak
CYP2D6 1388	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjE5OTE2In19	yes
P-gp 2052	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxOTkxNiJ9fQ==	yes
CYP3A4 1946	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjE5OTE2In19 \| https://pubmed.ncbi.nlm.nih.gov/22418831/	yes	yes (co-administration study) Comment: Itraconazole increased Cmax by 2.7-fold and AUCinf by 3.2-fold Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjE5OTE2In19 \| https://pubmed.ncbi.nlm.nih.gov/22418831/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 119	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/27861438/
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjE5OTE2In19

PubMed

Title	Date	PubMed
[Domperidone and hyperprolactinemia].	1998	10681812
Cardiovascular responses to intrathecal dopamine receptor agonists in conscious DOCA-salt hypertensive rats.	1999	10626749
Plasma cytokine concentration and the cytokine producing ability of whole blood cell cultures from healthy females with pharmacologically induced hyperprolactinemia.	1999	10568223
Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.	2000 Mar	10721819
Age-dependent effect of domperidone on dopamine release by the hypoxic carotid body in the rabbit.	2001	11585989
Dynamic dopamine-antagonist interactions at recombinant human dopamine D(2short) receptor: dopamine-bound versus antagonist-bound receptor states.	2001 Apr	11259537
Effect of adrenalectomy and dexamethasone treatment on prolactin secretion of lactating rats.	2001 Dec	11786246
Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction.	2001 Jan	11113639
Effects of gastrointestinal stimulant and suppressant pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic.	2001 Nov	11711265
Pharmacological characterization of cyclosporine A-induced kaolin intake in rats.	2001 Oct-Nov	11701197
Dopamine D(2) receptor activation causes mitogenesis via p44/42 mitogen-activated protein kinase in opossum kidney cells.	2001 Sep	11518777
Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women.	2002	12182236
Role of tyrosine kinase and p44/42 MAPK in D(2)-like receptor-mediated stimulation of Na(+), K(+)-ATPase in kidney.	2002 Apr	11880331
Acitretin-associated thrombotic stroke.	2002 Dec	12452748
New insight into the functional role of acetylcholine in developing embryonic rat retinal neurons.	2002 Feb	11818389
Dopaminergic modulation of ventilation in obese Zucker rats.	2002 Jan	11744639
Pro-erectile effect of systemic apomorphine: existence of a spinal site of action.	2002 Jan	11743364
KDR-5169, a new gastrointestinal prokinetic agent, enhances gastric contractile and emptying activities in dogs and rats.	2002 Jan 11	11779580
Determination of domperidone in human plasma by LC-MS and its pharmacokinetics in healthy Chinese volunteers.	2002 Mar	11918857
Gastric emptying in diabetes: clinical significance and treatment.	2002 Mar	11918620
Protective effect of dopamine D2 agonists in cortical neurons via the phosphatidylinositol 3 kinase cascade.	2002 Nov 1	12391586
Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer.	2002 Nov 4	12402144
Severe ventricular arrhythmia and sudden death on neuroleptics.	2002 Oct	12378746
Blunted central bromocriptine-induced tachycardia in conscious, malnourished rats.	2003 Apr	12753422
Substrate-dependent regulation of MAO-A in rat mesangial cells: involvement of dopamine D2-like receptors.	2003 Jan	12388421
Determination of ambroxol in human plasma using LC-MS/MS.	2003 Jun 1	12763530
Spectrophotometric methods for the determination of anti-emetic drugs in bulk and in pharmaceutical preparations.	2003 May	12769377
Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion.	2003 May	12662352

Patents

Sample Use Guides

In Vivo Use Guide

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

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

Name

Type

Language

DOMPERIDONE MALEATE

Common Name

English

DOMPERIDONE (AS MALEATE)

Preferred Name

English

DOMPERIDONE MALEATE [EP MONOGRAPH]

Common Name

English

Domperidone maleate [WHO-DD]

Common Name

English

DOMPERIDONE MALEATE [MART.]

Common Name

English

5-CHLORO-1-(1-(3-(2-OXOBENZIMIDAZOLIN-1-YL)PROPYL)-4-PIPERIDYL)BENZIMIDAZOLIN-2-ONE MALEATE

Systematic Name

English

Code System Code Type Description

DRUG BANK

DBSALT002902