NEOSTIGMINE

First marketed in 1931

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H19N2O2
Molecular Weight	223.2915
Optical Activity	NONE
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)C(=O)OC1=CC(=CC=C1)[N+](C)(C)C

InChI

InChIKey=ALWKGYPQUAPLQC-UHFFFAOYSA-N

InChI=1S/C12H19N2O2/c1-13(2)12(15)16-11-8-6-7-10(9-11)14(3,4)5/h6-9H,1-5H3/q+1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB01400
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/neostigmine-methylsulfate-injection.html

Neostigmine is a cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. By inhibiting acetylcholinesterase, more acetylcholine is available in the synapse, therefore, more of it can bind to the fewer receptors present in myasthenia gravis and can better trigger muscular contraction. Neostigmine is used for the symptomatic treatment of myasthenia gravis by improving muscle tone.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acetylcholinesterase 209 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8978837	Inhibitor 8504		91.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Myasthenia gravis 21 Sources: https://www.drugs.com/cdi/prostigmin.html	Primary		Approved 8583	Prostigmin Approved Use Neostigmine is used for: Treating myasthenia gravis. Launch Date 1938

C_max

Value	Dose	Co-administered	Analyte	Population
300 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/382915/	0.07 mg/kg single, intravenous dose: 0.07 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NEOSTIGMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
69.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/382915/	0.07 mg/kg single, intravenous dose: 0.07 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NEOSTIGMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
79.8 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/382915/	0.07 mg/kg single, intravenous dose: 0.07 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NEOSTIGMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204078s007lbl.pdf	0.03 mg/kg single, intravenous dose: 0.03 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NEOSTIGMINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
75% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204078s007lbl.pdf	0.03 mg/kg single, intravenous dose: 0.03 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NEOSTIGMINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 227

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A 317	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11913717/	yes		yes (co-administration study) Comment: information obtained from abstract: AUC of coadministered drug, parathion, parathion was significantly greater than control (65.1 versus 74.3 microg min/ml) Sources: https://pubmed.ncbi.nlm.nih.gov/11913717/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7514	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7514
eMolecules	31796384	https://www.emolecules.com/cgi-bin/more?vid=31796384
ZINC	ZINC000000001792	http://zinc15.docking.org/substances/ZINC000000001792

PubMed

Title	Date	PubMed
Antagonism of succinylcholine paralysis in a patient with atypical pseudocholinesterase.	1972 May	5021954
Neuropharmacology of the parasitic trematode, Schistosoma mansoni.	1983 Jan	6130710
Refractory bradycardia after reversal of muscle relaxant in a diabetic with vagal neuropathy.	1986 Nov	3767025
Prolonged bradycardia and hypotension after neostigmine administration in a patient receiving atenolol.	1987 Dec	3434760
Portal hypertension secondary to azathioprine in myasthenia gravis.	1988 Dec	3256814
Impairment of the antagonism of vecuronium-induced paralysis and intra-operative disopyramide administration.	1989 Jan	2564745
Complete heart block following glycopyrronium/neostigmine mixture.	1989 May	2742112
Sensitivity to both vecuronium and neostigmine in a sero-negative myasthenic patient.	1989 Oct	2573388
Reversal of antihypertensive agent-induced postural hypotension with physostigmine.	1991 May-Jun	1665057
Effects of adrenergic blockers on central nervous system-mediated hyperglycemia in fed rats.	1992 May	1350317
Subarachnoid neostigmine does not affect blood pressure or heart rate during bupivacaine spinal anesthesia.	1996 Nov-Dec	8956398
Effect of long-term administration of berberine on scopolamine-induced amnesia in rats.	1997 Jul	9268086
Postoperative reparalysis after rocuronium following nebulized epinephrine.	1997 Mar	9067054
Effect of glyceryl trinitrate on the sphincter of Oddi spasm evoked by prostigmine-morphine administration.	1997 Nov	9431903
A multi-center study of intrathecal neostigmine for analgesia following vaginal hysterectomy.	1998 Oct	9778009
[Prevention and release of epidural-morphine-induced urinary retention with phenoxybenzamine and neostigmine].	2000 Dec	12903414
Factors affecting gallbladder motility: drugs.	2003 Jul	12974504
Safety of enteral naloxone and i.v. neostigmine when used to relieve constipation.	2003 Jun 15	12845923
Heart block and prolonged Q-Tc interval following muscle relaxant reversal: a case report.	2008 Feb	18323319
The effect of piroxicam on the formation of postoperative, intraabdominal adhesion in rats.	2008 Oct	19568538
Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing.	2008 Sep	18559352

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose range of Neostigmine Methylsulfate Injection is 0.03 mg/kg to 0.07 mg/kg administered as an intravenous bolus.

Route of Administration: Intravenous

In Vitro Use Guide

In vitro, neostigmine (10⁻⁵ and 10⁻⁴ M) potentiated neurogenic relaxations in the rabbit corpus cavernosum.

Name

Type

Language

NEOSTIGMINE

Common Name

English

NEOSTIGMINE (CATION)

Preferred Name

English

NEOSTIGMINE [VANDF]

Common Name

English

NEOSTIGMINE ION

Common Name

English

BENZENAMINIUM, 3-(((DIMETHYLAMINO)CARBONYL)OXY)-N,N,N-TRIMETHYL-

Systematic Name

English

NEOSTIGMINE [MI]

Common Name

English

NEOSTIGMINE CATION

Common Name

English

NEOSTIGMINE [HSDB]

Common Name

English

NEOSTIGMINE [MART.]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N07AA01