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=C(OC)C=C(N)C(Cl)=C1

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

Molecular Formula	C14H22ClN3O2
Molecular Weight	299.796
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 2637
Muscarinic acetylcholine receptor M3 158 Target ID: CHEMBL320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15105209	Antagonist 2737	24.0 µM [IC50]
Dopamine D2 receptor 290 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB01233	Antagonist 2737	100.0 nM [IC50]
Serotonin 3a (5-HT3a) receptor 46 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16041395	Agonist 2637	0.064 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastroesophageal reflux disease 61 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017854s058lbl.pdf	Primary		Approved 8307	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 3.46896007E11
Diabetic gastroparesis 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017854s058lbl.pdf	Palliative		Approved 8307	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 3.46896007E11

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 1670		substrate 1168 inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1013

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1826	inhibitor 3185 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 1168	substrate 3264 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 1013	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor
CYP3A4 1670	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 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
MolPort	MolPort-000-883-854	https://www.molport.com/shop/molecule-link/MolPort-000-883-854
ZINC	ZINC000001530716	http://zinc15.docking.org/substances/ZINC000001530716
eMolecules	877442	https://www.emolecules.com/cgi-bin/more?vid=877442

PubMed

Title	Date	PubMed
Metoclopramide and pimozide in Parkinson's disease and levodopa-induced dyskinesias.	1975 Apr	1095689
Cloning, expression, and characterization of ferret 5-HT(3) receptor subunit.	2000 Jul 7	10884508
Tetanus-like syndrome secondary to metoclopramide administration.	2000 Oct-Dec	11202633
Mongolian spots with involvement of the temporal area.	2001 Apr	11454090
Ondansetron versus dehydrobenzoperidol and metoclopramide for management of postoperative nausea in laparoscopic surgery patients.	2001 Apr-Jun	11394426
Variation in practice patterns of anesthesiologists in California for prophylaxis of postoperative nausea and vomiting.	2001 Aug	11498316
Prevention of vomiting after general anesthesia for pediatric ophthalmic surgery.	2001 Feb	11759137
Metoclopramide versus ondansetron in prophylaxis of nausea and vomiting for laparoscopic cholecystectomy.	2001 Feb	11425054
Galactorrhoea, hyperprolactinaemia, and protease inhibitors.	2001 Feb 10	11273089
Prevention of postoperative nausea and vomiting with antiemetics in patients undergoing middle ear surgery: comparison of a small dose of propofol with droperidol or metoclopramide.	2001 Jan	11177010
Gastroparesis following bone marrow transplantation.	2001 Jul	11498745
Preparation and in vivo evaluation of parenteral metoclopramide-loaded poly(alkylcyanoacrylate) nanospheres in rats.	2001 Jul-Aug	11428676
Pre-emptive metoclopramide and ondansetron for nausea and vomiting associated with iloprost infusions.	2001 Jun	11468879
Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection.	2001 Jun	11422107
Gastric emptying in the critically ill.	2001 Jun	11395631
Gastroesophageal reflux medications in the treatment of apnea in premature infants.	2001 Mar	11241042
Effects of i.v. metoclopramide, atropine and their combination on gastric insufflation in children anaesthetized with sevoflurane and nitrous oxide.	2001 Mar	11240871
Central bromocriptine-induced tachycardia is reversed to bradycardia in conscious, deoxycorticosterone acetate-salt hypertensive rats.	2001 May	11393583
Nasty shock after an anti-emetic.	2001 May	11328920
AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.	2001 Nov	11711261
Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome.	2001 Nov	11701732
Low-dose dexamethasone effectively prevents postoperative nausea and vomiting after ambulatory laparoscopic surgery.	2001 Nov	11698315
In vitro release of metoclopramide from hydrophobic matrix tablets. influence of hydrodynamic conditions on kinetic release parameters.	2001 Oct	11605652
Preoperative diagnosis and localization of aldosterone-producing adenoma by adrenal venous sampling after administration of metoclopramide.	2001 Sep	11695274
Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction.	2002 Jan	11816261

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

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:31:01 UTC 2022` Edited by `admin` on `Fri Dec 16 16:31:01 UTC 2022`
Record UNII	L4YEB44I46
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METOCLOPRAMIDE

Official Name

English

METOCLOPRAMIDE [HSDB]

Common Name

English

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

Common Name

English

ELIETEN

Brand 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