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

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
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
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
[Pheochromocytoma with severe paralytic ileus occurred from acute pulmonary edema caused by metoclopramide].	2001 Aug 10	11573274
[Acute dystonia caused by metoclopramide (Afipran) therapy].	2001 Aug 10	11571992
Gastroparesis: prevalence, clinical significance and treatment.	2001 Dec	11773947
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
Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide-dexamethasone-lorazepam in the control of cisplatin induced emesis.	2001 Jul	11759977
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
Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.	2001 Jul 7	11440936
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
Gastric residual volume in children: a study comparing efficiency of erythromycin and metoclopramide as prokinetic agents.	2001 Jun	11573597
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
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
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
Dopaminergic modulation of human bronchial tone.	2001 Mar-Apr	11343812
Effect of transitory hyperprolactinemia on in vitro fertilization of human oocytes.	2001 May	11396370
A simple method to investigate the inhibitory effects of drugs on gastric emptying in the mouse in vivo.	2001 May-Jun	11755388
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
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
Endoscopic balloon dilation of benign esophageal strictures in dogs and cats.	2001 Nov-Dec	11817059
Initial experience with the stretta procedure for the treatment of gastroesophageal reflux disease.	2001 Oct	11642661
Preoperative diagnosis and localization of aldosterone-producing adenoma by adrenal venous sampling after administration of metoclopramide.	2001 Sep	11695274
Prevention of postoperative nausea and vomiting after laparoscopic gynaecological surgery. Combined antiemetic treatment with tropisetron and metoclopramide vs. metoclopramide alone.	2001 Sep	11553257
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
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

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