METOCLOPRAMIDE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H22ClN3O2.ClH.H2O
Molecular Weight	354.273
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of METOCLOPRAMIDE HYDROCHLORIDE

Structure Search

SMILES

O.Cl.CCN(CC)CCNC(=O)C1=C(OC)C=C(N)C(Cl)=C1

InChI

InChIKey=KJBLQGHJOCAOJP-UHFFFAOYSA-N

InChI=1S/C14H22ClN3O2.ClH.H2O/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);1H;1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

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

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

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
Letter: Involuntary facial movements.	1975 Mar 29	1125690
[Extrapyramidal reactions after epidural droperidol].	2000 Oct	11075569
Tetanus-like syndrome secondary to metoclopramide administration.	2000 Oct-Dec	11202633
Pharmacological options for the treatment of Tourette's disorder.	2001	11772131
Erythromycin as a gastrointestinal prokinetic agent.	2001 Apr	11817442
Placebo-controlled comparison of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in patients undergoing hysterectomy.	2001 Apr	11350463
Variation in practice patterns of anesthesiologists in California for prophylaxis of postoperative nausea and vomiting.	2001 Aug	11498316
Persistent hiccup associated with thoracic epidural injection.	2001 Aug	11475484
Nonulcer Dyspepsia.	2001 Aug	11469990
[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
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
[Prevention of postoperative nausea and vomiting in gynecologic surgery with 3 fixed doses of metoclopramide, droperidol or placebo].	2001 Feb	11257953
What is the optimal strategy for managing acute migraine headaches?	2001 Feb	11219568
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
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
Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide-dexamethasone-lorazepam in the control of cisplatin induced emesis.	2001 Jul	11759977
Pharmacoeconomic issues of the treatment of gastroesophageal reflux disease.	2001 Jul	11583061
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
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
Reproductive experience modulates dopamine-related behavioral responses.	2001 Mar	11325414
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 transitory hyperprolactinemia on in vitro fertilization of human oocytes.	2001 May	11396370
Laryngospasm: an atypical manifestation of severe gastroesophageal reflux disease (GERD).	2001 Nov	11801981
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
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
Comparing the efficacy of prophylactic metoclopramide, ondansetron, and placebo in cesarean section patients given epidural anesthesia.	2001 Sep	11578887
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
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
Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction.	2002 Jan	11816261
Why not to use erythromycin in GI motility.	2002 Jan	11796472

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 16:01:11 UTC 2022` Edited by `admin` on `Fri Dec 16 16:01:11 UTC 2022`
Record UNII	W1792A2RVD
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

METOCLOPRAMIDE HYDROCHLORIDE

Official Name

English

METOCLOPRAMIDE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

METOCLOPRAMIDE MONOHYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

METOZOLV ODT

Brand Name

English

METOCLOPRAMIDE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

NSC-757117

Code

English

REGLAN

Brand Name

English

METOCLOPRAMIDE HYDROCHLORIDE MONOHYDRATE [EP MONOGRAPH]

Common Name

English

METOCLOPRAMIDI HYDROCHLORIDUM [WHO-IP LATIN]

Common Name

English

CLOPRA

Brand Name

English

METIPAMID

Brand Name

English

Metoclopramide hydrochloride [WHO-DD]

Common Name

English

METOCLOPRAMIDE HYDROCHLORIDE MONOHYDRATE

Common Name

English

METOCLOPRAMIDE HYDROCHLORIDE [USP-RS]

Common Name

English

METOCLOPRAMIDE HYDROCHLORIDE [VANDF]

Common Name

English

GIMOTI

Brand Name

English

Metipamid [WHO-DD]

Common Name

English

METOCLOPRAMIDE HCL MONOHYDRATE

Common Name

English

AHR-3070-C

Code

English

4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-O-anisamide monohydrochloride monohydrate

Common Name

English

MAXOLON

Brand Name

English

METOCLOPRAMIDE HYDROCHLORIDE [WHO-IP]

Common Name

English

Metoclopramide hydrochloride monohydrate [WHO-DD]

Common Name

English

METOCLOPRAMIDE HYDROCHLORIDE [EP IMPURITY]

Common Name

English

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

Common Name

English

METOCLOPRAMIDE HYDROCHLORIDE [USAN]

Common Name

English

METOCLOPRAMIDE MONOHYDROCHLORIDE MONOHYDRATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C267