METOCLOPRAMIDE HYDROCHLORIDE ANHYDROUS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H22ClN3O2.ClH
Molecular Weight	336.2577
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of METOCLOPRAMIDE HYDROCHLORIDE ANHYDROUS

Structure Search

SMILES

CCN(CC)CCN=C(c1cc(c(cc1OC)N)Cl)O.Cl

InChI

InChIKey=RVFUNJWWXKCWNS-UHFFFAOYSA-N

InChI=1S/C14H22ClN3O2.ClH/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

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.4609
Charge	0
Count

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

Molecular Formula	C14H22ClN3O2
Molecular Weight	299.7969
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 160 Target ID: CHEMBL216 Sources: http://www.drugbank.ca/drugs/DB01233	Agonist 2470
Muscarinic acetylcholine receptor M3 151 Target ID: CHEMBL320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15105209	Antagonist 2575	24.0 µM [IC50]
Dopamine D2 receptor 283 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB01233	Antagonist 2575	100.0 nM [IC50]
Serotonin 3a (5-HT3a) receptor 44 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16041395	Agonist 2470	0.064 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastroesophageal reflux disease 45 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017854s058lbl.pdf	Primary		Approved 8043	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 8043	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 1601		substrate 1118 inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 972

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1738	inhibitor 3045 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 1118	substrate 3113 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 972	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor
CYP3A4 1601	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027056/	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 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
Letter: Involuntary facial movements.	1975 Mar 29	1125690
Pharmacological options for the treatment of Tourette's disorder.	2001	11772131
Ondansetron: a review of its use as an antiemetic in children.	2001	11437189
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
An endogenous 5-HT(7) receptor mediates pigment granule dispersion in Xenopus laevis melanophores.	2001 Apr	11309252
Variation in practice patterns of anesthesiologists in California for prophylaxis of postoperative nausea and vomiting.	2001 Aug	11498316
Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors.	2001 Aug	11489465
Persistent hiccup associated with thoracic epidural injection.	2001 Aug	11475484
Nonulcer Dyspepsia.	2001 Aug	11469990
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
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
[Prevention of postoperative nausea and vomiting in gynecologic surgery with 3 fixed doses of metoclopramide, droperidol or placebo].	2001 Feb	11257953
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
Gastroparesis following bone marrow transplantation.	2001 Jul	11498745
[Sinus arrest after the administration of intravenous metoclopramide].	2001 Jul 14	11481103
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
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
Supraglottic dystonic reaction to metoclopramide in a child.	2001 Jun 4	11453338
Reproductive experience modulates dopamine-related behavioral responses.	2001 Mar	11325414
Gastroesophageal reflux medications in the treatment of apnea in premature infants.	2001 Mar	11241042
Dopaminergic modulation of human bronchial tone.	2001 Mar-Apr	11343812
Effect of ATP sensitive potassium channel modifiers on antinociceptive effect of metoclopramide.	2001 May	11510133
Study of drug release from pellets coated with Surelease containing hydroxypropylmethylcellulose.	2001 May	11448049
Central bromocriptine-induced tachycardia is reversed to bradycardia in conscious, deoxycorticosterone acetate-salt hypertensive rats.	2001 May	11393583
Ondansetron rather than metoclopramide for bupropion-induced nausea.	2001 May	11387797
Impact of antiemetic selection on postoperative nausea and vomiting and patient satisfaction.	2001 May	11349743
Nasty shock after an anti-emetic.	2001 May	11328920
Initial experience with the stretta procedure for the treatment of gastroesophageal reflux disease.	2001 Oct	11642661
Efficacy of metoclopramide in postoperative ileus after exploratory laparotomy.	2001 Oct	11601663
Preoperative diagnosis and localization of aldosterone-producing adenoma by adrenal venous sampling after administration of metoclopramide.	2001 Sep	11695274
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
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

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 `Sat Jun 26 03:48:16 UTC 2021` Edited by `admin` on `Sat Jun 26 03:48:16 UTC 2021`
Record UNII	7B1QZY5SWZ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METOCLOPRAMIDE HYDROCHLORIDE ANHYDROUS

Common Name

English

NSC-354467

Code

English

METOCLOPRAMIDE HCL

Common Name

English

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

Common Name

English

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

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66883