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 169 Target ID: CHEMBL216 Sources: http://www.drugbank.ca/drugs/DB01233	Agonist 2678
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15105209	Antagonist 2778	24.0 µM [IC50]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB01233	Antagonist 2778	100.0 nM [IC50]
Serotonin 3a (5-HT3a) receptor 46 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16041395	Agonist 2678	0.064 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastroesophageal reflux disease 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017854s058lbl.pdf	Primary		Approved 8429	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 8429	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 1737		substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1891	inhibitor 3277 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 1217	substrate 3367 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 1054	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor
CYP3A4 1737	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
Drug-induced motor complications in dopa-responsive dystonia: implications for the pathogenesis of dyskinesias and motor fluctuations.	1999 Jul-Aug	10442251
[Complete heart block induced by intravenous metoclopramide].	2000 Apr	10893782
[Hypertensive crisis caused by metoclopramide].	2000 Jan-Feb	10916355
Cloning, expression, and characterization of ferret 5-HT(3) receptor subunit.	2000 Jul 7	10884508
Ondansetron: a review of its use as an antiemetic in children.	2001	11437189
Erythromycin as a gastrointestinal prokinetic agent.	2001 Apr	11817442
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
[Acute treatment of infantile headache].	2001 Aug 1-15	11588717
[Acute dystonia caused by metoclopramide (Afipran) therapy].	2001 Aug 10	11571992
RP-HPLC method with electrochemical detection for the determination of metoclopramide in serum and its use in pharmacokinetic studies.	2001 Dec	11748686
[Evaluation and treatment of hyperemesis gravidarum].	2001 Dec	11723426
Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache.	2001 Dec	11719739
Gastroesophageal reflux in infants and children.	2001 Dec 1	11764863
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
Effects of dopamine antagonists in human eye accommodation.	2001 Feb	11322633
Evaluation of the effective drugs for the prevention of nausea and vomiting induced by morphine used for postoperative pain: a quantitative systematic review.	2001 Feb	11218733
Galactorrhoea, hyperprolactinaemia, and protease inhibitors.	2001 Feb 10	11273089
Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide-dexamethasone-lorazepam in the control of cisplatin induced emesis.	2001 Jul	11759977
Preparation and in vivo evaluation of parenteral metoclopramide-loaded poly(alkylcyanoacrylate) nanospheres in rats.	2001 Jul-Aug	11428676
The cardiovascular effects of metoclopramide in multiple system atrophy and pure autonomic failure.	2001 Jun	11605821
Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection.	2001 Jun	11422107
Metoclopramide-induced methemoglobinemia in a patient with co-existing deficiency of glucose-6-phosphate dehydrogenase and NADH-cytochrome b5 reductase: failure of methylene blue treatment.	2001 Jun	11418378
Reproductive experience modulates dopamine-related behavioral responses.	2001 Mar	11325414
Gastroesophageal reflux medications in the treatment of apnea in premature infants.	2001 Mar	11241042
Nasty shock after an anti-emetic.	2001 May	11328920
A simple method to investigate the inhibitory effects of drugs on gastric emptying in the mouse in vivo.	2001 May-Jun	11755388
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
One thousand small-bowel biopsies in children. A single-port versus a double-port capsule.	2001 Nov	11686227
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
[ Ambulatory laparoscopic gynecological surgery in Africa: feasibility].	2001 Sep	11598560
Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women.	2001 Sep	11561213
Prevention of postoperative nausea and vomiting after laparoscopic gynaecological surgery. Combined antiemetic treatment with tropisetron and metoclopramide vs. metoclopramide alone.	2001 Sep	11553257
Metoclopramide-related pisa syndrome in clozapine treatment.	2001 Summer	11514658
Comparison of ondansetron with metoclopramide in the symptomatic relief of uremia-induced nausea and vomiting.	2002	11834879
[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management].	2002 Feb	11823926
Acute dystonia due to metoclopramide: increased risk in AIDS.	2002 Feb 11	11822933
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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:12:49 GMT 2023` Edited by `admin` on `Fri Dec 15 15:12:49 GMT 2023`
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