METOCLOPRAMIDE DIHYDROCHLORIDE MONOHYDRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H22ClN3O2.2ClH.H2O
Molecular Weight	390.734
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of METOCLOPRAMIDE DIHYDROCHLORIDE MONOHYDRATE

Structure Search

SMILES

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

InChI

InChIKey=IRQVJPHZDYMXNW-UHFFFAOYSA-N

InChI=1S/C14H22ClN3O2.2ClH.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);2*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	C14H22ClN3O2
Molecular Weight	299.796
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

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
Acute dystonia due to metoclopramide: increased risk in AIDS.	2002-02-11	11822933
[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management].	2002-02	11823926
Endoscopic balloon dilation of benign esophageal strictures in dogs and cats.	2002-01-31	11817059
A simple method to investigate the inhibitory effects of drugs on gastric emptying in the mouse in vivo.	2002-01-05	11755388
Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction.	2002-01	11816261
Why not to use erythromycin in GI motility.	2002-01	11796472
Effect of prolactin and dopaminergic drugs on uterine response to chronic estrogen exposure.	2002-01	11786374
Physical compatibility and in vivo evaluation of drug mixtures for subcutaneous infusion to cancer patients in palliative care.	2002-01	11777190
Comparison of ondansetron with metoclopramide in the symptomatic relief of uremia-induced nausea and vomiting.	2002	11834879
Gastroesophageal reflux in infants and children.	2001-12-01	11764863
Gastroparesis: prevalence, clinical significance and treatment.	2001-12	11773947
RP-HPLC method with electrochemical detection for the determination of metoclopramide in serum and its use in pharmacokinetic studies.	2001-12	11748686
[Evaluation and treatment of hyperemesis gravidarum].	2001-12	11723426
Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache.	2001-12	11719739
Laryngospasm: an atypical manifestation of severe gastroesophageal reflux disease (GERD).	2001-11	11801981
Comparison of cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition in critically III, mechanically ventilated adults.	2001-11	11768837
AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.	2001-11	11711261
Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome.	2001-11	11701732
Low-dose dexamethasone effectively prevents postoperative nausea and vomiting after ambulatory laparoscopic surgery.	2001-11	11698315
One thousand small-bowel biopsies in children. A single-port versus a double-port capsule.	2001-11	11686227
[Acute treatment of infantile headache].	2001-10-06	11588717
Initial experience with the stretta procedure for the treatment of gastroesophageal reflux disease.	2001-10	11642661
In vitro release of metoclopramide from hydrophobic matrix tablets. influence of hydrodynamic conditions on kinetic release parameters.	2001-10	11605652
Efficacy of metoclopramide in postoperative ileus after exploratory laparotomy.	2001-10	11601663
Preoperative diagnosis and localization of aldosterone-producing adenoma by adrenal venous sampling after administration of metoclopramide.	2001-09	11695274
[ Ambulatory laparoscopic gynecological surgery in Africa: feasibility].	2001-09	11598560
Comparing the efficacy of prophylactic metoclopramide, ondansetron, and placebo in cesarean section patients given epidural anesthesia.	2001-09	11578887
Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women.	2001-09	11561213
Prevention of postoperative nausea and vomiting after laparoscopic gynaecological surgery. Combined antiemetic treatment with tropisetron and metoclopramide vs. metoclopramide alone.	2001-09	11553257
[Pheochromocytoma with severe paralytic ileus occurred from acute pulmonary edema caused by metoclopramide].	2001-08-10	11573274
[Acute dystonia caused by metoclopramide (Afipran) therapy].	2001-08-10	11571992
Variation in practice patterns of anesthesiologists in California for prophylaxis of postoperative nausea and vomiting.	2001-08	11498316
Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors.	2001-08	11489465
Persistent hiccup associated with thoracic epidural injection.	2001-08	11475484
Nonulcer Dyspepsia.	2001-08	11469990
[Sinus arrest after the administration of intravenous metoclopramide].	2001-07-14	11481103
Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide-dexamethasone-lorazepam in the control of cisplatin induced emesis.	2001-07	11759977
Pharmacoeconomic issues of the treatment of gastroesophageal reflux disease.	2001-07	11583061
Gastroparesis following bone marrow transplantation.	2001-07	11498745
[Prophylaxis of nausea and vomiting after thyroid surgery: comparison of oral and intravenous dolasetron with intravenous droperidol and placebo].	2001-07	11496617
Supraglottic dystonic reaction to metoclopramide in a child.	2001-06-04	11453338
The cardiovascular effects of metoclopramide in multiple system atrophy and pure autonomic failure.	2001-06	11605821
Gastric residual volume in children: a study comparing efficiency of erythromycin and metoclopramide as prokinetic agents.	2001-06	11573597
Pre-emptive metoclopramide and ondansetron for nausea and vomiting associated with iloprost infusions.	2001-06	11468879
Effect of ATP sensitive potassium channel modifiers on antinociceptive effect of metoclopramide.	2001-05	11510133
Erythromycin as a gastrointestinal prokinetic agent.	2001-04	11817442
Mongolian spots with involvement of the temporal area.	2001-04	11454090
Prevention of vomiting after general anesthesia for pediatric ophthalmic surgery.	2001-02	11759137
Pharmacological options for the treatment of Tourette's disorder.	2001	11772131
Metoclopramide-related pisa syndrome in clozapine treatment.	2001	11514658

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 `Mon Mar 31 21:55:55 GMT 2025` Edited by `admin` on `Mon Mar 31 21:55:55 GMT 2025`
Record UNII	W1KXE205VU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BENZAMIDE, 4-AMINO-5-CHLORO-N-(2-(DIETHYLAMINO)ETHYL)-2-METHOXY-, HYDROCHLORIDE, HYDRATE (1:2:1)

Preferred Name

English

METOCLOPRAMIDE DIHYDROCHLORIDE MONOHYDRATE

Common Name

English

METOCLOPRAMIDE HYDROCHLORIDE [JAN]

Common Name

English

Metoclopramide dihydrochloride monohydrate [WHO-DD]

Common Name

English

Code System Code Type Description

CAS

5581-45-3