Identification

Name
Metoclopramide
Accession Number
DB01233  (APRD00665)
Type
Small Molecule
Groups
Approved, Investigational
Description

A dopamine D2 antagonist that is used as an antiemetic.

Structure
Thumb
Synonyms
  • 2-methoxy-4-amino-5-chloro-N,N-(dimethylaminoethyl)benzamide
  • 2-methoxy-5-chloroprocainamide
  • 4-amino-5-chloro-2-methoxy-N-(β-diethylaminoethyl)benzamide
  • 4-amino-5-chloro-N-(2-(diethylamino)ethyl)-o-anisamide
  • Metoclopramida
  • Metoclopramidum
Product Ingredients
IngredientUNIICASInChI Key
Metoclopramide hydrochloride7B1QZY5SWZ7232-21-5RVFUNJWWXKCWNS-UHFFFAOYSA-N
Metoclopramide hydrochloride monohydrateW1792A2RVD54143-57-6KJBLQGHJOCAOJP-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Maxeran 5mg TabTablet5 mgOralLabs Nordic Laboratories Inc. Subsidary Of M.M.D.C.1984-12-311998-08-12Canada
Maxeran LiqLiquid1 mgOralHoechst Marion Roussel1995-12-312000-07-28Canada
Maxeran-10 (10mg Tablet)Tablet10 mgOralHoechst Marion Roussel1995-12-312000-07-28Canada
Maxeran-5 (5mg Tablet)Tablet5 mgOralHoechst Marion Roussel1996-10-232000-07-28Canada
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousGeneral Injectables & Vaccines2010-08-012017-01-17Us
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousCardinal Health2010-12-092013-03-31Us
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousBaxter Laboratories2010-12-092013-04-30Us
Metoclopramide Hydrochloride InjectionLiquid5 mgIntramuscular; IntravenousSandoz Canada Incorporated1995-12-31Not applicableCanada
Metoclopramide Hydrochloride Injection HsLiquid5 mgIntravenousBioniche Pharma (Canada) Ltd1999-04-192014-09-11Canada
Metoclopramide OmegaLiquid5 mgIntramuscular; IntravenousOmega Laboratories Ltd2001-04-30Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-metoclop Tab 10mgTablet10 mgOralApotex Corporation1989-12-31Not applicableCanada
Apo-metoclop Tab 5mgTablet5 mgOralApotex Corporation1989-12-31Not applicableCanada
MetoclopramideTablet10 mg/1OralTeva1990-09-30Not applicableUs0093 220320180814 13942 19b27lu
MetoclopramideTablet10 mg/1OralAmerincan Health Packaging2005-08-082015-01-31Us
MetoclopramideTablet10 mg/1OralNucare Pharmaceuticals, Inc.1990-09-30Not applicableUs
MetoclopramideTablet10 mg/1OralNucare Pharmaceuticals,inc.1985-10-17Not applicableUs
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousGeneral Injectables & Vaccines2010-05-01Not applicableUs
MetoclopramideSolution5 mg/5mLOralAtlantic Biologicals Corps1991-06-01Not applicableUs
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousHospira Worldwide, Inc.1989-03-032009-04-05Us
MetoclopramideTablet5 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs2011-11-18Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
MetoclopramideMetoclopramide hydrochloride monohydrate (5 mg/1mL)Injection, solutionIntramuscular; IntravenousHospira, Inc.2008-05-142008-05-14Us
MetoclopramideMetoclopramide hydrochloride monohydrate (5 mg/1)TabletOralVintage Pharmaceuticals, LLC2007-09-132007-09-13Us
MetoclopramideMetoclopramide hydrochloride monohydrate (5 mg/5mL)SolutionOralANI Pharmaceuticals Inc.2008-10-022008-10-02Us
MetoclopramideMetoclopramide hydrochloride monohydrate (10 mg/1)TabletOralVintage Pharmaceuticals, LLC2007-09-132007-09-13Us
PCP 100 KitMetoclopramide hydrochloride monohydrate (10 mg/1) + Bisacodyl (5 mg/1) + Magnesium citrate (1.745 g/29.6mL) + Petrolatum (0.76 g/1g) + Polyethylene glycol (17 g/17g)KitOral; TopicalAsclemed Usa, Inc.2014-01-02Not applicableUs
International/Other Brands
Cerucal / Degan / Elieten / Maxeran / Maxolon / METOZOLV / Plasil1 / Plazilin / Pramin / Primperan / Pulin / Pylomid / Reliveran
Categories
UNII
L4YEB44I46
CAS number
364-62-5
Weight
Average: 299.796
Monoisotopic: 299.14005467
Chemical Formula
C14H22ClN3O2
InChI Key
TTWJBBZEZQICBI-UHFFFAOYSA-N
InChI
InChI=1S/C14H22ClN3O2/c1-4-18(5-2)7-6-17-14(19)10-8-11(15)12(16)9-13(10)20-3/h8-9H,4-7,16H2,1-3H3,(H,17,19)
IUPAC Name
4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide
SMILES
CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC

Pharmacology

Indication

For the treatment of gastroesophageal reflux disease (GERD). It is also used in treating nausea and vomiting, and to increase gastric emptying.

Associated Conditions
Associated Therapies
Pharmacodynamics

Metoclopramide, although chemically related to procainamide, does not possess local anesthetic or antiarrhythmic properties. Metoclopramide is used to enhance GI motility, to treat diabetic gastroparesis, as an antinauseant, and to facilitate intubation of the small bowel during radiologic examination. Metoclopramide may be used to treat chemotherapy-induced emesis and as a radiosensitizing agents in the treatment of non-small cell lung carcinoma and glioblastomas in the future.

Mechanism of action

Metoclopramide inhibits gastric smooth muscle relaxation produced by dopamine, therefore increasing cholinergic response of the gastrointestinal smooth muscle. It accelerates intestinal transit and gastric emptying by preventing relaxation of gastric body and increasing the phasic activity of antrum. Simultaneously, this action is accompanied by relaxation of the upper small intestine, resulting in an improved coordination between the body and antrum of the stomach and the upper small intestine. Metoclopramide also decreases reflux into the esophagus by increasing the resting pressure of the lower esophageal sphincter and improves acid clearance from the esophagus by increasing amplitude of esophageal peristaltic contractions. Metoclopramide's dopamine antagonist action raises the threshold of activity in the chemoreceptor trigger zone and decreases the input from afferent visceral nerves. Studies have also shown that high doses of metoclopramide can antagonize 5-hydroxytryptamine (5-HT) receptors in the peripheral nervous system in animals.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AMuscarinic acetylcholine receptor M1
agonist
Human
U5-hydroxytryptamine receptor 4
agonist
Human
U5-hydroxytryptamine receptor 3A
agonist
Human
UAcetylcholinesterase
inhibitor
Human
Absorption

Rapidly and well absorbed (oral bioavailability 80±15.5%).

Volume of distribution
  • 4.4±0.65 L/kg
Protein binding

30%

Metabolism

Hepatic

Route of elimination

Approximately 85% of the radioactivity of an orally administered dose appears in the urine within 72 hours.

Half life

5-6 hr

Clearance
  • 0.67 +/- 0.14 L/hr/kg [infants (0.9-5.4 months) with gastroesophageal reflux (GER)]
Toxicity

Oral, mouse LD50: 280 mg/kg. Signs of overdose include drowsiness, disorientation, and extrapyramidal reactions.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Potassium voltage-gated channel subfamily H member 2---(C;C) / (A;C)A > CEffect Directly StudiedThe presence of this polymorphism in KCNH2 may be associated with increased clinical efficacy with metoclopramide.Details
Alpha-1D adrenergic receptor---(T;T) / (A;T)A > TEffect Directly StudiedThe presence of this polymorphism in ADRA1D may be associated with increased clinical efficacy with metoclopramide.Details
Cytochrome P450 2D6CYP2D6*2A(G;G) / (C;G)C > GADR Directly StudiedPatients with this genotype have reduced metabolism of metoclopramide and may be at a higher risk of experiencing adverse events.Details
Cytochrome P450 2D6CYP2D6*2(A;A) / (A;G)G > AADR Directly StudiedPatients with this genotype have reduced metabolism of metoclopramide and may be at a higher risk of experiencing adverse events.Details
Cytochrome P450 2D6CYP2D6*4(A;A) / (A;G)G > ADirectly Studied EffectPatients with this genotype have reduced metabolism of metoclopramide.Details
Potassium voltage-gated channel subfamily H member 2---(T;T) / (C;T)G > AADR Directly StudiedThe presence of this polymorphism in KCNH2 is associated with higher incidences of adverse events from metoclopramide treatment.Details
Multidrug resistance protein 1---(T;T) / (C;T) / (T;T) / (G;T) / (T;T) / (C;T)T Allele / G > T  … show all Effect Directly StudiedPatients with this polymorphism in ABCB1 may have a reduced response to clomipramine.Details
NADH-cytochrome b5 reductase 3---Not AvailableExon 2 c.129C>A / Exon 2 c.149G>A  … show all ADR InferredRisk of methemglobinemia.Details

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe therapeutic efficacy of (2-benzhydryloxyethyl)diethyl-methylammonium iodide can be decreased when used in combination with Metoclopramide.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Metoclopramide is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Metoclopramide is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Metoclopramide.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Metoclopramide is combined with 4-Bromo-2,5-dimethoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Metoclopramide is combined with 5-methoxy-N,N-dimethyltryptamine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of serotonin syndrome can be increased when Metoclopramide is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbexinostatThe risk or severity of QTc prolongation can be increased when Metoclopramide is combined with Abexinostat.
AcebutololMetoclopramide may increase the bradycardic activities of Acebutolol.
AcepromazineThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Acepromazine.
Food Interactions
  • Food reduces availability, take 30 minutes before meals. Avoid alcohol.

References

Synthesis Reference
US3177252
General References
  1. JUSTIN-BESANCON L, LAVILLE C: [ANTIEMETIC ACTION OF METOCLOPRAMIDE WITH RESPECT TO APOMORPHINE AND HYDERGINE]. C R Seances Soc Biol Fil. 1964;158:723-7. [PubMed:14186927]
  2. Tonini M, Candura SM, Messori E, Rizzi CA: Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis. Pharmacol Res. 1995 May;31(5):257-60. [PubMed:7479521]
External Links
Human Metabolome Database
HMDB0015363
KEGG Drug
D00726
KEGG Compound
C07868
PubChem Compound
4168
PubChem Substance
46505631
ChemSpider
4024
BindingDB
48320
ChEBI
107736
ChEMBL
CHEMBL86
Therapeutic Targets Database
DAP000530
PharmGKB
PA450475
IUPHAR
241
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Metoclopramide
ATC Codes
A03FA01 — Metoclopramide
AHFS Codes
  • 56:32.00 — Prokinetic Agents
FDA label
Download (90.1 KB)
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticHemorrhage, Gastrointestinal1
1TerminatedBasic ScienceDrug Metabolism, Poor, CYP2D6-RELATED1
1, 2CompletedTreatmentEnteral Feeding Intolerance (EFI)1
1, 2CompletedTreatmentPost-Traumatic Headaches1
2CompletedPreventionOpioid Analgesic Adverse Reaction / Traumas1
2CompletedTreatmentDelayed Gastric Emptying / Diabetes Mellitus (DM) / Diabetic Gastroparesis / Gastroparesis1
2CompletedTreatmentEnteral Feeding Intolerance (EFI)1
2CompletedTreatmentInfant, Newborn, Diseases1
2CompletedTreatmentMigraine Disorders1
2CompletedTreatmentMigrainous Headache1
2Not Yet RecruitingPreventionPost Anaesthetic Shivering1
2RecruitingTreatmentCritical Illness / Enteral Feeding Intolerance (EFI) / Nutrition, Enteral1
2RecruitingTreatmentNuclear radiation emergency / Nutrition, Enteral1
2TerminatedSupportive CareVomiting1
2TerminatedTreatmentBenign Headache1
2TerminatedTreatmentGastroparesis1
2WithdrawnTreatmentMyelodysplastic Syndromes1
2, 3WithdrawnTreatmentHeadaches1
3CompletedSupportive CareNausea and Vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentBreastfeeding1
3CompletedTreatmentClozapine-induced Hypersalivation1
3CompletedTreatmentElective Caesarean Section Surgeries1
3CompletedTreatmentHeadaches / Intranasal Ketamine1
3CompletedTreatmentMigraines1
3Enrolling by InvitationTreatmentAutonomic Nervous System Diseases / Dopamine Beta-Hydroxylase Deficiency / Idiopathic orthostatic hypotension / Orthostatic Intolerance1
3Not Yet RecruitingTreatmentAcute Gastroenteritis / Vomiting1
3RecruitingPreventionChemotherapy Induced Vomiting / Leukemia Acute Myeloid Leukemia (AML)1
3RecruitingTreatmentGastroschisis1
3RecruitingTreatmentHyperemesis Gravidarum1
3RecruitingTreatmentNausea / Vomiting1
3RecruitingTreatmentPost-Traumatic Headaches1
3RecruitingTreatmentTumors, Solid1
3TerminatedPreventionSepsis1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3TerminatedTreatmentVomiting1
3Unknown StatusDiagnosticHemorrhage, Gastrointestinal / Refractory Anemia / Small Bowel Diseases1
3Unknown StatusPreventionNausea / Vomiting1
3WithdrawnTreatmentMigraines1
4CompletedNot AvailablePill Capsule Endoscopy Completion Rates1
4CompletedPreventionInfants, Premature1
4CompletedPreventionMigraines1
4CompletedPreventionNausea / Satisfaction / Vomiting1
4CompletedPreventionPregnancy1
4CompletedPreventionProlonged First Stage of Labor1
4CompletedTreatmentHeadaches1
4CompletedTreatmentMigraine Disorders1
4CompletedTreatmentMigraine With Aura / Migraine Without Aura / Probable Migraine1
4CompletedTreatmentMigraine, Acute1
4CompletedTreatmentMigraines2
4CompletedTreatmentMigrainous Headache1
4CompletedTreatmentMigrainous Headache / Nausea / Restlessness1
4CompletedTreatmentNausea / Vertigo / Vomiting1
4CompletedTreatmentNausea / Vomiting1
4CompletedTreatmentExtra-pyramidal symptoms / Nausea1
4CompletedTreatmentOpioid Induced Pharyngeal and Esophageal Dysfunction1
4CompletedTreatmentPostoperative Function Level / Postoperative pain / Prophylaxis against postoperative nausea and vomiting1
4Not Yet RecruitingPreventionProphylaxis against postoperative nausea and vomiting1
4Not Yet RecruitingTreatmentCancers / Nausea / Vomiting1
4Not Yet RecruitingTreatmentReflux, Gastroesophageal1
4RecruitingPreventionLaparoscopic Sleeve Gastrectomy / Prophylaxis against postoperative nausea and vomiting1
4RecruitingTreatmentAcute Myocardial Infarction (AMI)1
4RecruitingTreatmentMigraines1
4RecruitingTreatmentOpiate withdrawal symptoms1
4RecruitingTreatmentST Segment Elevation Myocardial Infarction (STEMI)1
4SuspendedTreatmentMigrainous Headache1
Not AvailableCompletedNot AvailableRhytidoplasty1
Not AvailableCompletedDiagnosticColorectal Cancer Screening1
Not AvailableCompletedDiagnosticGastric Transit Time1
Not AvailableCompletedPreventionAkathisia / Nausea1
Not AvailableCompletedPreventionCesarean Delivery1
Not AvailableCompletedPreventionHeadaches1
Not AvailableCompletedPreventionProphylaxis against postoperative nausea and vomiting1
Not AvailableCompletedTreatmentBreastfeeding1
Not AvailableCompletedTreatmentCancers1
Not AvailableNot Yet RecruitingTreatmentAssisted Reproductive Technology therapy / Poor Responder1
Not AvailableNot Yet RecruitingTreatmentPoor Responders in IVF1
Not AvailableRecruitingBasic ScienceHealth1
Not AvailableRecruitingTreatmentHigh Altitude Headache / Other and unspecified effects of high altitude1
Not AvailableRecruitingTreatmentMigrainous Headache1
Not AvailableTerminatedTreatmentFeeding Disorder / Infants, Premature / Nutrition Disorder1
Not AvailableTerminatedTreatmentNausea1
Not AvailableTerminatedTreatmentPrimary Headaches (Includes Migraines, Tension, Cluster Headaches)1
Not AvailableUnknown StatusSupportive CareNon-Hodgkin's Lymphoma (NHL)1
Not AvailableUnknown StatusTreatmentPost Concussive Headache / Post Concussive Syndrome1
Not AvailableWithdrawnTreatmentPost Operative Nausea and Vomiting (PONV) / Rescue Emetic Therapy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Alaven Pharmaceutical
  • Almus Pharmaceuticals Usa LLC
  • Amerisource Health Services Corp.
  • Anip Acquisition Co.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Baxter International Inc.
  • Bay Pharma Inc.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Duramed
  • General Injectables and Vaccines Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Innoviant Pharmacy Inc.
  • Ipca Laboratories Ltd.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Neighborcare Repackaging Inc.
  • Neuman Distributors Inc.
  • Northstar Rx LLC
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • Pharmaceutical Association
  • Pharmaceutical Packaging Center
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Piramal Healthcare
  • Pliva Inc.
  • Precision Dose Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepak Systems Inc.
  • Qualitest
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Salix Pharmaceuticals
  • Sandhills Packaging Inc.
  • Sandoz
  • Silarx Pharmaceuticals
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Vangard Labs Inc.
  • Viasys Medsystems
  • Vintage Pharmaceuticals Inc.
  • Vistapharm Inc.
  • Watson Pharmaceuticals
  • Wockhardt Ltd.
  • Xactdose Inc.
Dosage forms
FormRouteStrength
LiquidOral1 mg
InjectionIntramuscular; Intravenous5 mg/1mL
Injection, solutionIntramuscular; Intravenous10 mg/2mL
Injection, solutionIntramuscular; Intravenous5 mg/1mL
SolutionOral0.9 mg/0.9mL
SolutionOral10 mg/10mL
SolutionOral5 mg/5mL
TabletOral10 mg/1
TabletOral5 mg/1
Injection, solutionIntravenous5 mg/1mL
Tablet, orally disintegratingOral10 mg/1
Tablet, orally disintegratingOral5 mg/1
LiquidIntramuscular; Intravenous5 mg
LiquidIntravenous5 mg
SolutionOral5 mg
TabletOral10 mg
TabletOral5 mg
KitOral; Topical
Injection, solutionIntramuscular; Intravenous5.0 mg/1.0mL
SyrupOral1 mg
Prices
Unit descriptionCostUnit
Metoclopramide hcl powder7.65USD g
Reglan 10 mg tablet1.81USD tablet
Reglan 5 mg tablet1.41USD tablet
Metoclopramide Hydrochloride 5 mg/ml1.39USD ml
Reglan 5 mg/ml vial0.56USD ml
Metoclopramide HCl 5 mg tablet0.43USD tablet
Metoclopramide 5 mg tablet0.33USD tablet
Metoclopramide 10 mg tablet0.28USD tablet
Metoclopramide 5 mg/ml ampul0.28USD ml
Metoclopramide HCl 10 mg tablet0.27USD tablet
Metoclopramide HCl 5 mg/5ml Solution0.06USD ml
Apo-Metoclop 10 mg Tablet0.06USD tablet
Apo-Metoclop 5 mg Tablet0.06USD tablet
Nu-Metoclopramide 10 mg Tablet0.06USD tablet
Nu-Metoclopramide 5 mg Tablet0.06USD tablet
Pms-Metoclopramide 10 mg Tablet0.06USD tablet
Pms-Metoclopramide 5 mg Tablet0.06USD tablet
Pms-Metoclopramide 1 mg/ml Liquid0.04USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6221392No1998-04-092018-04-09Us
US6024981No1998-04-092018-04-09Us
US6413549No1997-07-112017-07-11Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)147.25 °CPhysProp
water solubility200 mg/L (at 25 °C)MERCK (1989)
logP2.62HANSCH,C ET AL. (1995)
logS-3.18ADME Research, USCD
pKa9.27 (at 25 °C)EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.31 mg/mLALOGPS
logP2.18ALOGPS
logP1.4ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)14.49ChemAxon
pKa (Strongest Basic)9.04ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.59 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity83.52 m3·mol-1ChemAxon
Polarizability32.7 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.979
Blood Brain Barrier+0.9713
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.7687
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8783
Renal organic cation transporterNon-inhibitor0.7276
CYP450 2C9 substrateNon-substrate0.8602
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.6375
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9099
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6223
Ames testNon AMES toxic0.5378
CarcinogenicityNon-carcinogens0.6142
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6332 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8367
hERG inhibition (predictor II)Inhibitor0.8579
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-10fdf9db1550886fc034
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-fcc278321866ecdee26f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0193000000-c044c04d9d51d66ba5a9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0290000000-45d3c52d766c4cd8ae93
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-003r-0970000000-2f2d709cad2c27f798e5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0920000000-ccce0f42f04edf0ecfb3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00lr-0900000000-93aec7dddb8a098f7483
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-e7b25ddf867c24be5347
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0093000000-dc0ce524de60c6a189a7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0290000000-2bca02d9f4cee5acca4e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-003r-0970000000-50fe530dffb9aa59d433
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0920000000-0bb9973fdbe0820dc3d1
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00lr-0900000000-4cc6fae9bec9d4c40dbb
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-1c4a27b221c7a053d2c3
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0fb9-0595000000-db3b50f051cfcc835a69

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminophenyl ethers. These are aromatic compounds that contain a phenol ether, which carries an amine group on the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Aminophenyl ethers
Direct Parent
Aminophenyl ethers
Alternative Parents
Methoxyanilines / Phenoxy compounds / Methoxybenzenes / Anisoles / Chlorobenzenes / Alkyl aryl ethers / Aryl chlorides / Trialkylamines / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids
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Substituents
Aminophenyl ether / Methoxyaniline / Phenoxy compound / Anisole / Methoxybenzene / Aniline or substituted anilines / Alkyl aryl ether / Chlorobenzene / Halobenzene / Aryl chloride
show 20 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, substituted aniline, benzamides, monochlorobenzenes (CHEBI:107736)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. See RE, Lynch AM, Sorg BA: Subchronic administration of clozapine, but not haloperidol or metoclopramide, decreases dopamine D2 receptor messenger RNA levels in the nucleus accumbens and caudate-putamen in rats. Neuroscience. 1996 May;72(1):99-104. [PubMed:8730709]
  3. Harrold MW, Sriburi A, Matsumoto K, Miller DD, Farooqui T, Uretsky N: The interaction of ammonium, sulfonium, and sulfide analogues of metoclopramide with the dopamine D2 receptor. J Med Chem. 1993 Oct 15;36(21):3166-70. [PubMed:8230103]
  4. Kishibayashi N, Karasawa A: Stimulating effects of KW-5092, a novel gastroprokinetic agent, on the gastric emptying, small intestinal propulsion and colonic propulsion in rats. Jpn J Pharmacol. 1995 Jan;67(1):45-50. [PubMed:7745844]
  5. Chemnitius JM, Haselmeyer KH, Gonska BD, Kreuzer H, Zech R: Indirect parasympathomimetic activity of metoclopramide: reversible inhibition of cholinesterases from human central nervous system and blood. Pharmacol Res. 1996 Jul-Aug;34(1-2):65-72. [PubMed:8981558]
  6. Dahlof CG, Hargreaves RJ: Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies? Cephalalgia. 1998 Nov;18(9):593-604. [PubMed:9876882]
  7. Hammer D: Gastroesophageal reflux and prokinetic agents. Neonatal Netw. 2005 Mar-Apr;24(2):51-8; quiz 59-62. [PubMed:15835479]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Burger DM, Wiestner T, Hubler M, Binder H, Keiser M, Arnold S: Effect of anticholinergics (atropine, glycopyrrolate) and prokinetics (metoclopramide, cisapride) on gastric motility in beagles and labrador retrievers. J Vet Med A Physiol Pathol Clin Med. 2006 Mar;53(2):97-107. [PubMed:16466463]
  4. Hammer D: Gastroesophageal reflux and prokinetic agents. Neonatal Netw. 2005 Mar-Apr;24(2):51-8; quiz 59-62. [PubMed:15835479]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR4
Uniprot ID
Q13639
Uniprot Name
5-hydroxytryptamine receptor 4
Molecular Weight
43760.975 Da
References
  1. Guillemot J, Compagnon P, Cartier D, Thouennon E, Bastard C, Lihrmann I, Pichon P, Thuillez C, Plouin PF, Bertherat J, Anouar Y, Kuhn JM, Yon L, Lefebvre H: Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors. Endocr Relat Cancer. 2009 Mar;16(1):281-90. doi: 10.1677/ERC-08-0190. Epub 2008 Oct 23. [PubMed:18948374]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Voltage-gated potassium channel activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. Costall B, Gunning SJ, Naylor RJ, Tyers MB: The effect of GR38032F, novel 5-HT3-receptor antagonist on gastric emptying in the guinea-pig. Br J Pharmacol. 1987 Jun;91(2):263-4. [PubMed:2955843]
Details
5. Acetylcholinesterase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
reversible inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Petroianu G, Arafat K, Kosanovic M, Saleh A, Camasamudram V, Hasan MY: In vitro protection of red blood cell acetylcholinesterase by metoclopramide from inhibition by organophosphates (paraoxon and mipafox). J Appl Toxicol. 2003 Nov-Dec;23(6):447-51. [PubMed:14635269]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Gene Name
CYP11B2
Uniprot ID
P19099
Uniprot Name
Cytochrome P450 11B2, mitochondrial
Molecular Weight
57559.62 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 17-alpha-monooxygenase activity
Specific Function
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation ...
Gene Name
CYP17A1
Uniprot ID
P05093
Uniprot Name
Steroid 17-alpha-hydroxylase/17,20 lyase
Molecular Weight
57369.995 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on September 21, 2018 20:42