Details of the Drug

General Information of Drug (ID: DMBDPY0)

Drug Name
Domperidone
Synonyms
Domperidon; Domperidona; Domperidonum; Motilium; Nauzelin; KW 5338; NCI299589; Costi (TN); D-122; Domperidona [INN-Spanish]; Domperidonum [INN-Latin]; HS-0067; KW-5338; Motilium (TN); Motillium (TN); Motinorm (TN); R 33,812; R-33812; R-33,812; Domperidone (JAN/USAN/INN); Domperidone [USAN:BAN:INN:JAN]; 4-(5-Chloro-2-oxo-1-benzimidazolinyl)-1-[3-(2-oxobenzimidazolinyl)propyl]piperidine; 5-Chloro-1-(1-(3-(2-oxo-1-benzimidazolinyl)propyl)-4-piperidyl)-2-benzimidazolinone; 5-Chloro-1-[1-[3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one; 5-Chloro-1-[1-[3-(2-oxo-1-benzimidazolinyl)propyl]-4-piperidyl]-2-benzimidazolinone; 5-chloro-1-(1-(3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)propyl)-4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one; 5-chloro-1-{1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)propyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one; 6-chloro-3-[1-[3-(2-oxo-3H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1H-benzimidazol-2-one
Indication
Disease Entry ICD 11 Status REF
Gastrointestinal disease DE2Z Approved [1]
Gastroparesis DA41.00 Approved [2]
Therapeutic Class
Antiemetics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 425.9
Logarithm of the Partition Coefficient (xlogp) 3.9
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Clearance
The drug present in the plasma can be removed from the body at the rate of 9.5 mL/min/kg [4]
Elimination
0% of drug is excreted from urine in the unchanged form [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 7 hours [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3354 micromolar/kg/day [5]
Unbound Fraction
The unbound fraction of drug in plasma is 0.082% [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 3.4 L/kg [4]
Water Solubility
The ability of drug to dissolve in water is measured as 0.006 mg/mL [3]
Chemical Identifiers
Formula
C22H24ClN5O2
IUPAC Name
6-chloro-3-[1-[3-(2-oxo-3H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1H-benzimidazol-2-one
Canonical SMILES
C1CN(CCC1N2C3=C(C=C(C=C3)Cl)NC2=O)CCCN4C5=CC=CC=C5NC4=O
InChI
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)
InChIKey
FGXWKSZFVQUSTL-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
3151
ChEBI ID
CHEBI:31515
CAS Number
57808-66-9
DrugBank ID
DB01184
TTD ID
D0AV3G
VARIDT ID
DR00963
INTEDE ID
DR0527
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Antagonist [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [10]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [9]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [9]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [10]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Drug Response [11]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Drug Response [11]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Gene/Protein Processing [12]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Biotransformations [9]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Biotransformations [9]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Biotransformations [9]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Biotransformations [9]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Gene/Protein Processing [13]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Gene/Protein Processing [14]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Gene/Protein Processing [15]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Gastrointestinal disease
ICD Disease Classification DE2Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Dopamine D2 receptor (D2R) DTT DRD2 2.50E-02 -0.08 -0.49
P-glycoprotein 1 (ABCB1) DTP P-GP 9.39E-02 1.07E-01 2.80E-01
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 1.82E-04 -1.35E-01 -5.84E-01
Cytochrome P450 2B6 (CYP2B6) DME CYP2B6 4.88E-01 -1.69E-05 -1.28E-04
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.36E-01 1.62E-02 1.08E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 9.96E-01 -3.17E-03 -1.84E-02
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 7.30E-01 -1.91E-02 -1.41E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 965).
2 Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013 Jan;108(1):18-37; quiz 38.
3 BDDCS applied to over 900 drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6 Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
7 Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates. J Pharm Pharmacol. 2004 Aug;56(8):967-75.
8 Characterization of CYP3A isozymes involved in the metabolism of domperidone: role of cytochrome b5 and inhibition by ketoconazole. Drug Metab Lett. 2010 Apr;4(2):95-103.
9 Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol. 2004 Sep;58(3):277-87.
10 Drug Interactions Flockhart Table
11 Domperidone treatment for gastroparesis: demographic and pharmacogenetic characterization of clinical efficacy and side-effects. Dig Dis Sci. 2011 Jan;56(1):115-24. doi: 10.1007/s10620-010-1472-2. Epub 2010 Nov 10.
12 Prediction of aryl hydrocarbon receptor-mediated enzyme induction of drugs and chemicals by mRNA quantification. Chem Res Toxicol. 1998 Dec;11(12):1447-52.
13 Plasma cytokine concentration and the cytokine producing ability of whole blood cell cultures from healthy females with pharmacologically induced hyperprolactinemia. Int J Tissue React. 1999;21(2):43-9.
14 Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
15 [Importance of prolactin level indication in detection of Sheehan syndrome]. Ginekol Pol. 1992 May;63(5):232-5.