METHYLATROPINE NITRATE

US Previously Marketed

First marketed in 1911

Details

Stereochemistry	EPIMERIC
Molecular Formula	C18H26NO3.NO3
Molecular Weight	366.4088
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[O-][N+]([O-])=O.C[N+]1(C)[C@H]2CC[C@@H]1C[C@@H](C2)OC(=O)C(CO)C3=CC=CC=C3

InChI

InChIKey=NEDVJZNVOSNSHF-KUMOIWDRSA-N

InChI=1S/C18H26NO3.NO3/c1-19(2)14-8-9-15(19)11-16(10-14)22-18(21)17(12-20)13-6-4-3-5-7-13;2-1(3)4/h3-7,14-17,20H,8-12H2,1-2H3;/q+1;-1/t14-,15+,16+,17?;

HIDE SMILES / InChI

Molecular Formula	NO3
Molecular Weight	62.0049
Charge	-1
Count

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

Molecular Formula	C18H26NO3
Molecular Weight	304.4039
Charge	1
Count

Stereochemistry	MIXED
Additional Stereochemistry	No
Defined Stereocenters	3 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21032188http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1987730/pdf/archdisch01465-0039.pdf

Methylatropine (methylatroponium) is a belladonna derivative. In 1902 the Bayer Company introduced atropine methonitrate, a quaternary ammonium salt of atropine (Eumydrin), as a mydriatic for dilation of the pupil during ophthalmic examination. Due to its highly polar nature it penetrates less readily into the central nervous system than atropine and was therefore introduced for relieving pyloric spasms in infants. Atropine methyl nitrate is a muscarinic acetylcholine receptor antagonist that does not cross the blood-brain barrier. Atropine methyl nitrate has been used for its peripheral muscarinic effects (targeting the bladder, respiratory tract, and to block parasympathetic signaling to the heart, among others) and to separate central from peripheral nervous system effects, or to protect against peripheral side effects when using muscarinics that do cross the blood brain barrier.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor 160 Target ID: CHEMBL2094109 Sources: DOI: 10.1021/jm980320h, Gyermek L., 'Pharmacology of Antimuscarinic Agents' (1997), p. 162, Retrieved from https://books.google.es/books?id=_VyDxfdunv4C&pg	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Pyloric stenosis 3 Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1987730/pdf/archdisch01465-0039.pdf	Curative	Preclinical	Unknown Approved Use Unknown
Eye diseases 25 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18799813	Diagnostic	Approved 8429	Eumydrin Approved Use Unknown Launch Date 1901
Pyloric stenosis 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21032188	Palliative	Approved 8429	Eumydrin Approved Use Unknown

Doses

Dose	Population	Adverse events
0.8 mg multiple, oral (total) Dose: 0.8 mg Route: oral Route: multiple Dose: 0.8 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	unhealthy, 1 week n = 1 Health Status: unhealthy Age Group: 1 week Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	Other AEs: Paralytic ileus, Hypotonic urinary bladder... Other AEs: Paralytic ileus (1 patient) Hypotonic urinary bladder (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6807409
0.4 mg 6 times / day multiple, oral Dose: 0.4 mg, 6 times / day Route: oral Route: multiple Dose: 0.4 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5909489	unhealthy, 2 month n = 1 Health Status: unhealthy Age Group: 2 month Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5909489	Other AEs: Dilated pupils, Fever... Other AEs: Dilated pupils Fever Sources: https://pubmed.ncbi.nlm.nih.gov/5909489
2.5 mL 1 times / day multiple, oral Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21032188	unhealthy, 37 days n = 1 Health Status: unhealthy Age Group: 37 days Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21032188	Other AEs: Paralytic ileus... Other AEs: Paralytic ileus (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/21032188
16 mg multiple, oral (total) Highest studied dose Dose: 16 mg Route: oral Route: multiple Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	unhealthy, 7 weeks n = 1 Health Status: unhealthy Age Group: 7 weeks Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	Other AEs: Irritable, Hypertonia... Other AEs: Irritable (1 patient) Hypertonia (1 patient) Dilated pupils (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6807409
0.1 mg 1 times / day multiple, oral (starting) Dose: 0.1 mg, 1 times / day Route: oral Route: multiple Dose: 0.1 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21032188	unhealthy, babies n = 15 Health Status: unhealthy Age Group: babies Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/21032188	Disc. AE: Abdominal distension... AEs leading to discontinuation/dose reduction: Abdominal distension Sources: https://pubmed.ncbi.nlm.nih.gov/21032188

AEs

AE	Significance	Dose	Population
Hypotonic urinary bladder	1 patient	0.8 mg multiple, oral (total) Dose: 0.8 mg Route: oral Route: multiple Dose: 0.8 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	unhealthy, 1 week n = 1 Health Status: unhealthy Age Group: 1 week Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6807409
Paralytic ileus	1 patient	0.8 mg multiple, oral (total) Dose: 0.8 mg Route: oral Route: multiple Dose: 0.8 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	unhealthy, 1 week n = 1 Health Status: unhealthy Age Group: 1 week Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6807409
Dilated pupils		0.4 mg 6 times / day multiple, oral Dose: 0.4 mg, 6 times / day Route: oral Route: multiple Dose: 0.4 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5909489	unhealthy, 2 month n = 1 Health Status: unhealthy Age Group: 2 month Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5909489
Fever		0.4 mg 6 times / day multiple, oral Dose: 0.4 mg, 6 times / day Route: oral Route: multiple Dose: 0.4 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5909489	unhealthy, 2 month n = 1 Health Status: unhealthy Age Group: 2 month Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5909489
Paralytic ileus	grade 5	2.5 mL 1 times / day multiple, oral Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21032188	unhealthy, 37 days n = 1 Health Status: unhealthy Age Group: 37 days Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21032188
Dilated pupils	1 patient	16 mg multiple, oral (total) Highest studied dose Dose: 16 mg Route: oral Route: multiple Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	unhealthy, 7 weeks n = 1 Health Status: unhealthy Age Group: 7 weeks Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6807409
Hypertonia	1 patient	16 mg multiple, oral (total) Highest studied dose Dose: 16 mg Route: oral Route: multiple Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	unhealthy, 7 weeks n = 1 Health Status: unhealthy Age Group: 7 weeks Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6807409
Irritable	1 patient	16 mg multiple, oral (total) Highest studied dose Dose: 16 mg Route: oral Route: multiple Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6807409	unhealthy, 7 weeks n = 1 Health Status: unhealthy Age Group: 7 weeks Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6807409
Abdominal distension	Disc. AE	0.1 mg 1 times / day multiple, oral (starting) Dose: 0.1 mg, 1 times / day Route: oral Route: multiple Dose: 0.1 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21032188	unhealthy, babies n = 15 Health Status: unhealthy Age Group: babies Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/21032188

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	6458AF
AK Scientific	6459AF
BOC Sciences	2870-71-5
BOC Sciences	52-88-0
Chem Scene	CS-0043286
ChemDiv	6264-0458
Chemieliva Pharmaceutical Co., Ltd	PBCM1271376
Compound Cloud	23724526
Compound Cloud	656597
Compound Cloud	656598
Compound Cloud	656864
Compound Cloud	657381
Enamine	EN300-312881
Hairui	HR142467
Hairui	HR144203
IBScreen	STOCK1N-27068
IBScreen	STOCK1N-93371
Lab Network	395
Lab Network	LN01753260
Lab Network	LN01755054
MedChem Express	HY-112076
MolPort	MolPort-000-703-558
MolPort	MolPort-000-711-438
MolPort	MolPort-009-758-008
MolPort	MolPort-039-140-487
MolPort	MolPort-044-179-469
MuseChem	M010675
MuseChem	R034282
NCI Plated 2007	61810
Pharmeks	PHAR009239
Pharmeks	PHAR018930
Princeton BioMolecular Research	OSSK_579999
Scientific Exchange	F-035069
TimTec	ST51039050
Vitas-M Laboratory	STK108600
ZINC	ZINC000001620937	http://zinc15.docking.org/substances/ZINC000001620937
ZINC	ZINC000012466871	http://zinc15.docking.org/substances/ZINC000012466871
ZINC	ZINC000012466998	http://zinc15.docking.org/substances/ZINC000012466998
ZINC	ZINC000100371013	http://zinc15.docking.org/substances/ZINC000100371013
ZINC	ZINC000100371018	http://zinc15.docking.org/substances/ZINC000100371018
eMolecules	104671449
eMolecules	35780000
eMolecules	36091971
eMolecules	50420744
eMolecules	7349288
mcule	MCULE-1521238572
mcule	MCULE-7662254879

PubMed

Title	Date	PubMed
Clinical pertussis treated with methyl atropine nitrate (eumydrin).	1950 Oct 7	14778526
Ganglionic blocking action of atropine and methylatropine.	1953 Dec	13109700
The difference in the effects of tertiary and quaternary ammonium bases (proserine, serine, methylatropine and atropine) depending on the method of administration.	1962 Mar	14038511
Analysis of cardiac chronotropic responses to diazepam and bromazepam in conscious trained dogs.	1976 Feb	2483
Influence of several anesthetic agents on the effect of delta9-tetrahydrocannabinol on the heart rate and blood pressure of the mongrel dog.	1977 Jul 1	885163
Participation of cholinergic pathways in sinoaortic denervated rats.	1985	3996883
Apparent reduction in baroreflex sensitivity to adenosine in conscious dogs.	1985 Sep	3929624
Investigation into the cardioregulatory properties of the alpha 1-adrenoceptor blocker indoramin.	1986 Feb	3955309
Central interactions between dihydropyridines and cholinergic systems in the control of blood pressure in rat.	1987 Dec 1	2448012
L-glutamate stimulation of the zona incerta in the rat decreases heart rate and blood pressure.	1988 Aug 16	2905195
Endogenous gamma-aminobutyric acid (GABA) mediates ethanol inhibition of vagally mediated reflex bradycardia elicited from aortic baroreceptors.	1994 Feb	8113962
The role of cholinergic systems in the expression of morphine withdrawal.	1996 Jun	8829152
Bupivacaine inhibits baroreflex control of heart rate in conscious rats.	2000 Jan	10638917
Central muscarinic receptors signal pilocarpine-induced salivation.	2003 Dec	14630901
Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate.	2003 Dec	14561847
Cardiac effects of hypocretin-1 in nucleus ambiguus.	2003 Jun	12573979
Inhibition of [18F]FP-TZTP binding by loading doses of muscarinic agonists P-TZTP or FP-TZTP in vivo is not due to agonist-induced reduction in cerebral blood flow.	2003 Nov	12923818
Dual effects of acupuncture on gastric motility in conscious rats.	2003 Oct	12959921
Pharmacologic evidence for a parasympathetic role in seizure-induced neurocardiac regulatory abnormalities.	2004 Feb	14751203
Effects of angiotensin II on autonomic components of nasopharyngeal stimulation in male conscious rabbits.	2005 May	15649867
Effects of AV3V lesion on pilocarpine-induced pressor response and salivary gland vasodilation.	2005 Sep 7	16054600
Facilitation of cardiac vagal activity by CRF-R1 antagonists during swim stress in rats.	2006 Dec	16710322
Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats.	2006 Dec 11	17113926
Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors.	2006 Feb	16199474
Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX.	2007 Mar	17188727
Medullary pathways mediating the parasubthalamic nucleus depressor response.	2008 Apr	18287224
Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeability.	2008 Jan 2	18082973
Ghrelin infused into the portal vein inhibits glucose-stimulated insulin secretion in Wistar rats.	2008 Jul	18436343
Effect of ghrelin on glucose-insulin homeostasis: therapeutic implications.	2010	20700401
Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism.	2010 Jun 25	20421298
Final answer: ghrelin can suppress insulin secretion in humans, but is it clinically relevant?	2010 Nov	20980471

Patents

Sample Use Guides

In Vivo Use Guide

Pyloric stenosis: The first dose was usually 0.5-1 ml (0.05-0.1 mgm. per dose), increasing by 0.5 ml at each feed till a dose of 2-3 ml, six times daily, was reached, i.e. 1.2-1.8 mgm. in twenty-four hours.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:10:35 GMT 2023` Edited by `admin` on `Fri Dec 15 15:10:35 GMT 2023`
Record UNII	Q48D9J47K2
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

METHYLATROPINE NITRATE

Official Name

English

EKOMINE

Brand Name

English

ATROPINE METHYLNITRATE [MI]

Common Name

English

ATROPINE METHONITRATE [MART.]

Common Name

English

ATROPINE METHYL NITRATE

Common Name

English

atropine methonitrate [INN]

Common Name

English

ATROPINE METHYLNITRATE

Common Name

English

ATROPINE METHONITRATE

Official Name

English

Atropine methonitrate [WHO-DD]

Common Name

English

8-AZONIABICYCLO(3.2.1)OCTANE, 3-(3-HYDROXY-1-OXO-2-PHENYLPROPOXY)-8,8-DIMETHYL-, ENDO-(±)-, NITRATE (SALT)

Common Name

English

ATROPINE METHYLNITRATE [VANDF]

Common Name

English

ATROPINE METHONITRATE [JAN]

Common Name

English

NSC-759122

Code

English

8-METHYLATROPINIUM NITRATE

Common Name

English

METHYLATROPINE NITRATE [EP IMPURITY]

Common Name

English

EUMYDRIN

Brand Name

English

N-METHYLATROPINE NITRATE

Common Name

English

METHYLATROPINE NITRATE [USAN]

Common Name

English

Code System Code Type Description

EVMPD

SUB12156MIG