METOCLOPRAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H22ClN3O2
Molecular Weight	299.796
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC

InChI

InChIKey=TTWJBBZEZQICBI-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB01233
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017854s058lbl.pdf

Metoclopramide is a dopamine D2 antagonist that is used as an antiemetic. 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. Metoclopramide is used for the treatment of gastroesophageal reflux disease (GERD). It is also used in treating nausea and vomiting, and to increase gastric emptying.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL216 Sources: http://www.drugbank.ca/drugs/DB01233	Agonist 2752
Muscarinic acetylcholine receptor M3 160 Target ID: CHEMBL320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15105209	Antagonist 2849	24.0 µM [IC50]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB01233	Antagonist 2849	100.0 nM [IC50]
Serotonin 3a (5-HT3a) receptor 48 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16041395	Agonist 2752	0.064 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastroesophageal reflux disease 68 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017854s058lbl.pdf	Primary		Approved 8583	REGLAN Approved Use Symptomatic Gastroesophageal Reflux Reglan® tablets are indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy Diabetic Gastroparesis (Diabetic Gastric Stasis) Reglan® tablets (metoclopramide tablets, USP) is indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis. Launch Date 1980
Diabetic gastroparesis 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017854s058lbl.pdf	Palliative		Approved 8583	REGLAN Approved Use Symptomatic Gastroesophageal Reflux Reglan® tablets are indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy Diabetic Gastroparesis (Diabetic Gastric Stasis) Reglan® tablets (metoclopramide tablets, USP) is indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis. Launch Date 1980

C_max

Value	Dose	Co-administered	Analyte	Population
41 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209388s000lbl.pdf	15 mg single, nasal dose: 15 mg route of administration: Nasal experiment type: SINGLE co-administered:		METOCLOPRAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
367 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209388s000lbl.pdf	15 mg single, nasal dose: 15 mg route of administration: Nasal experiment type: SINGLE co-administered:		METOCLOPRAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209388s000lbl.pdf	15 mg single, nasal dose: 15 mg route of administration: Nasal experiment type: SINGLE co-administered:		METOCLOPRAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209388s000lbl.pdf	15 mg single, nasal dose: 15 mg route of administration: Nasal experiment type: SINGLE co-administered:		METOCLOPRAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1197

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017854s062lbl.pdf#page=15 Page: 15.0	likely		unlikely (co-administration study) Comment: metoclopramide is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017854s062lbl.pdf#page=15 Page: 15.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017854s062lbl.pdf#page=13 Page: 13.0	major	yes (co-administration study) Comment: patients who received concomitant metoclopramide and fluoxetine had a 40% and 90% increase in metoclopramide Cmax and AUC0-∞, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017854s062lbl.pdf#page=13 Page: 13.0
CYP1A2 1197	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor
CYP3A4 1946	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/15640612/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:107736	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:107736
eMolecules	877442	https://www.emolecules.com/cgi-bin/more?vid=877442
MolPort	MolPort-000-883-854	https://www.molport.com/shop/molecule-link/MolPort-000-883-854
ZINC	ZINC000001530716	http://zinc15.docking.org/substances/ZINC000001530716

PubMed

Title	Date	PubMed
Letter: Involuntary facial movements.	1975 Mar 29	1125690
Pharmacological options for the treatment of Tourette's disorder.	2001	11772131
Ondansetron: a review of its use as an antiemetic in children.	2001	11437189
Erythromycin as a gastrointestinal prokinetic agent.	2001 Apr	11817442
Mongolian spots with involvement of the temporal area.	2001 Apr	11454090
Placebo-controlled comparison of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in patients undergoing hysterectomy.	2001 Apr	11350463
Iatrogenic metoclopramide toxicity in an infant presenting to a pediatric emergency department.	2001 Apr	11334098
An endogenous 5-HT(7) receptor mediates pigment granule dispersion in Xenopus laevis melanophores.	2001 Apr	11309252
Ondansetron versus dehydrobenzoperidol and metoclopramide for management of postoperative nausea in laparoscopic surgery patients.	2001 Apr-Jun	11394426
Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors.	2001 Aug	11489465
[Acute treatment of infantile headache].	2001 Aug 1-15	11588717
Gastroparesis: prevalence, clinical significance and treatment.	2001 Dec	11773947
Metoclopramide versus ondansetron in prophylaxis of nausea and vomiting for laparoscopic cholecystectomy.	2001 Feb	11425054
Effects of dopamine antagonists in human eye accommodation.	2001 Feb	11322633
[Prevention of postoperative nausea and vomiting in gynecologic surgery with 3 fixed doses of metoclopramide, droperidol or placebo].	2001 Feb	11257953
Galactorrhoea, hyperprolactinaemia, and protease inhibitors.	2001 Feb 10	11273089
Galactorrhoea, hyperprolactinaemia, and protease inhibitors.	2001 Feb 10	11273088
Generalised seizures following ondansetron.	2001 Jan	11249042
Gastroparesis following bone marrow transplantation.	2001 Jul	11498745
[Prophylaxis of nausea and vomiting after thyroid surgery: comparison of oral and intravenous dolasetron with intravenous droperidol and placebo].	2001 Jul	11496617
[Sinus arrest after the administration of intravenous metoclopramide].	2001 Jul 14	11481103
The cardiovascular effects of metoclopramide in multiple system atrophy and pure autonomic failure.	2001 Jun	11605821
Gastric emptying in the critically ill.	2001 Jun	11395631
Serum prolactin is associated with apoptosis in men with human immunodeficiency virus infection.	2001 Jun	11380682
A spectrophotometric method for the determination of metoclopramide HCl and dapsone.	2001 Jun	11377044
Supraglottic dystonic reaction to metoclopramide in a child.	2001 Jun 4	11453338
Reproductive experience modulates dopamine-related behavioral responses.	2001 Mar	11325414
Gastroesophageal reflux medications in the treatment of apnea in premature infants.	2001 Mar	11241042
Small doses of propofol, droperidol, and metoclopramide for the prevention of postoperative nausea and vomiting after thyroidectomy.	2001 Mar	11240988
Effects of i.v. metoclopramide, atropine and their combination on gastric insufflation in children anaesthetized with sevoflurane and nitrous oxide.	2001 Mar	11240871
Induction of lactation in the intended mother of a surrogate pregnancy: case report.	2001 Mar	11228232
Comparison of granisetron, droperidol, and metoclopramide for prevention of postoperative vomiting in children with a history of motion sickness undergoing tonsillectomy.	2001 Mar	11226996
Dopaminergic modulation of human bronchial tone.	2001 Mar-Apr	11343812
Metoclopramide-induced akathisia during the second trimester of a 37-year-old woman's first pregnancy.	2001 Mar-Apr	11239130
Effect of ATP sensitive potassium channel modifiers on antinociceptive effect of metoclopramide.	2001 May	11510133
Study of drug release from pellets coated with Surelease containing hydroxypropylmethylcellulose.	2001 May	11448049
Central bromocriptine-induced tachycardia is reversed to bradycardia in conscious, deoxycorticosterone acetate-salt hypertensive rats.	2001 May	11393583
Ondansetron rather than metoclopramide for bupropion-induced nausea.	2001 May	11387797
Impact of antiemetic selection on postoperative nausea and vomiting and patient satisfaction.	2001 May	11349743
Nasty shock after an anti-emetic.	2001 May	11328920
Laryngospasm: an atypical manifestation of severe gastroesophageal reflux disease (GERD).	2001 Nov	11801981
Comparison of cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition in critically III, mechanically ventilated adults.	2001 Nov	11768837
Endoscopic balloon dilation of benign esophageal strictures in dogs and cats.	2001 Nov-Dec	11817059
In vitro release of metoclopramide from hydrophobic matrix tablets. influence of hydrodynamic conditions on kinetic release parameters.	2001 Oct	11605652
[ Ambulatory laparoscopic gynecological surgery in Africa: feasibility].	2001 Sep	11598560
Metoclopramide-related pisa syndrome in clozapine treatment.	2001 Summer	11514658
Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction.	2002 Jan	11816261
Why not to use erythromycin in GI motility.	2002 Jan	11796472
Effect of prolactin and dopaminergic drugs on uterine response to chronic estrogen exposure.	2002 Jan	11786374
Physical compatibility and in vivo evaluation of drug mixtures for subcutaneous infusion to cancer patients in palliative care.	2002 Jan	11777190

Patents

Sample Use Guides

In Vivo Use Guide

For the relief of Symptomatic Gastroesophageal Reflux Administer from 10 mg to 15 mg reglan® (metoclopramide hydrochloride, USP) orally up to q.i.d. 30 minutes before each meal and at bedtime, depending upon symptoms being treated and clinical response

Route of Administration: Oral

In Vitro Use Guide

200 nM metoclopramide led to 79% peak current suppression in HEK-293 cells

Name

Type

Language

ELIETEN

Preferred Name

English

METOCLOPRAMIDE

Official Name

English

METOCLOPRAMIDE [HSDB]

Common Name

English

4-AMINO-5-CHLORO-N-(2-(DIETHYLAMINO)ETHYL)-O-ANISAMIDE

Common Name

English

METOCLOPRAMIDE [JAN]

Common Name

English

METOCLOPRAMIDE [MART.]

Common Name

English

METOCLOPRAMIDE [MI]

Common Name

English

BENZAMIDE, 4-AMINO-5-CHLORO-N-(2-(DIETHYLAMINO)ETHYL)-2-METHOXY-

Systematic Name

English

METHOXYCLOPRAMIDE

Common Name

English

METOCLOPRAMIDE [EP MONOGRAPH]

Common Name

English

METOCLOPRAMIDE [VANDF]

Common Name

English

Metoclopramide [WHO-DD]

Common Name

English

metoclopramide [INN]

Common Name

English

TERPERAN

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C267