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Details

Stereochemistry ACHIRAL
Molecular Formula C28H42Cl2N4O2
Molecular Weight 537.5656
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 2

SHOW SMILES / InChI
Structure of AMBENONIUM

SMILES

CC[N+](CC)(CCN=C(C(=NCC[N+](CC)(CC)Cc1ccccc1Cl)O)O)Cc2ccccc2Cl

InChI

InChIKey=OMHBPUNFVFNHJK-UHFFFAOYSA-P
InChI=1S/C28H40Cl2N4O2/c1-5-33(6-2,21-23-13-9-11-15-25(23)29)19-17-31-27(35)28(36)32-18-20-34(7-3,8-4)22-24-14-10-12-16-26(24)30/h9-16H,5-8,17-22H2,1-4H3/p+2

HIDE SMILES / InChI
Ambenonium is a cholinesterase inhibitor with all the pharmacologic actions of acetylcholine, both the muscarinic and nicotinic types. It was marketed under the brand name Mytelase, but was withdrawn from the market in the United States in 2010. Ambenonium, similar to pyridostigmine and neostigmine, is used for the treatment of muscle weakness and fatigue in people with myasthenia gravis.Ambenonium exerts its actions against myasthenia gravis by competitive, reversible inhibition of acetylcholinesterase. The disease myasthenia gravis occurs when the body inappropriately produces antibodies against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission (when acetylcholine binds to acetylcholine receptors of striated muscle fibers, it stimulates those fibers to contract). Ambenonium reversibly binds acetylcholinesterase at the anionic site, which results in the blockage of the site of acetycholine binding, thereby inhibiting acetylcholine hydrolysis and enhancing cholinergic function through the accumulation of acetycholine at cholinergic synpases. In turn this facilitates transmission of impulses across the myoneural junction and effectively treats the disease.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MYTELASE

Approved Use

This drug is indicated for the treatment of myasthenia gravis.

Launch Date

-4.31395209E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.129 μg/mL
10 mg 4 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.812 μg/mL
5 mg 4 times / day multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
1.29 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
2.5 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
5.61 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.12 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8.4 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1.38 μg × h/mL
10 mg 4 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6.5 μg × h/mL
5 mg 4 times / day multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
0.112 μg × min/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
0.23 μg × min/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
0.5 μg × min/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1.07 μg × min/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMBENONIUM serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
5 mg 4 times / day multiple, oral
Dose: 5 mg, 4 times / day
Route: oral
Route: multiple
Dose: 5 mg, 4 times / day
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: chronic cystitis
Age Group: 31 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Muscle weakness, Fatigue...
AEs leading to
discontinuation/dose reduction:
Muscle weakness (1 patient)
Fatigue (1 patient)
Chest pain (1 patient)
Sources:
10 mg 3 times / 2 days multiple, oral
Dose: 10 mg, 3 times / 2 days
Route: oral
Route: multiple
Dose: 10 mg, 3 times / 2 days
Sources:
unhealthy, 81 years
n = 1
Health Status: unhealthy
Condition: pernicious anemia
Age Group: 81 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Muscle weakness, Nausea...
AEs leading to
discontinuation/dose reduction:
Muscle weakness (1 patient)
Nausea (1 patient)
Abdominal pain (1 patient)
Sources:
1000 mg 1 times / day multiple, oral
Studied dose
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
AEs

AEs

AESignificanceDosePopulation
Chest pain 1 patient
Disc. AE
5 mg 4 times / day multiple, oral
Dose: 5 mg, 4 times / day
Route: oral
Route: multiple
Dose: 5 mg, 4 times / day
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: chronic cystitis
Age Group: 31 years
Sex: F
Population Size: 1
Sources:
Fatigue 1 patient
Disc. AE
5 mg 4 times / day multiple, oral
Dose: 5 mg, 4 times / day
Route: oral
Route: multiple
Dose: 5 mg, 4 times / day
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: chronic cystitis
Age Group: 31 years
Sex: F
Population Size: 1
Sources:
Muscle weakness 1 patient
Disc. AE
5 mg 4 times / day multiple, oral
Dose: 5 mg, 4 times / day
Route: oral
Route: multiple
Dose: 5 mg, 4 times / day
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: chronic cystitis
Age Group: 31 years
Sex: F
Population Size: 1
Sources:
Abdominal pain 1 patient
Disc. AE
10 mg 3 times / 2 days multiple, oral
Dose: 10 mg, 3 times / 2 days
Route: oral
Route: multiple
Dose: 10 mg, 3 times / 2 days
Sources:
unhealthy, 81 years
n = 1
Health Status: unhealthy
Condition: pernicious anemia
Age Group: 81 years
Sex: F
Population Size: 1
Sources:
Muscle weakness 1 patient
Disc. AE
10 mg 3 times / 2 days multiple, oral
Dose: 10 mg, 3 times / 2 days
Route: oral
Route: multiple
Dose: 10 mg, 3 times / 2 days
Sources:
unhealthy, 81 years
n = 1
Health Status: unhealthy
Condition: pernicious anemia
Age Group: 81 years
Sex: F
Population Size: 1
Sources:
Nausea 1 patient
Disc. AE
10 mg 3 times / 2 days multiple, oral
Dose: 10 mg, 3 times / 2 days
Route: oral
Route: multiple
Dose: 10 mg, 3 times / 2 days
Sources:
unhealthy, 81 years
n = 1
Health Status: unhealthy
Condition: pernicious anemia
Age Group: 81 years
Sex: F
Population Size: 1
Sources:
PubMed

PubMed

TitleDatePubMed
Effects of acetylcholinesterase inhibitors on the metabolism of amyloid precursor protein in vitro.
2001
Differential inhibition of [3H]-oxotremorine-M and [3H]-quinuclinidyl benzilate binding to muscarinic receptors in rat brain membranes with acetylcholinesterase inhibitors.
2001 Apr
Reversible and irreversible acetylcholinesterase inhibitors cause changes in neuronal amyloid precursor protein processing and protein kinase C level in vitro.
2001 Mar
Thyroid gland tumour, pemphigus foliaceus and myasthenia gravis in the daughter of a woman with myasthenia gravis.
2001 Sep
Sequence of a cDNA encoding acetylcholinesterase from susceptible and resistant two-spotted spider mite, Tetranychus urticae.
2003 May
Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors.
2003 Sep
[Biochemical characteristics of cholinesterase from taenia Hymenolepis diminuta].
2004
Identification and quantitation of six non-depolarizing neuromuscular blocking agents by LC-MS in biological fluids.
2004 Mar
[Nephrotic syndrome after extended thymectomy for thymoma with myasthenia gravis; report of a case].
2006 Mar
Similarities between CSF-brain extracellular transfer and neurofibrillary tangle invasion in Alzheimer's disease.
2006 Mar
Activation of group II metabotropic glutamate receptors reduces directional selectivity in retinal ganglion cells.
2006 Nov 29
Concurrence of non-myasthenic symptoms with myasthenia gravis.
2007 Apr
Characterization of reversible and pseudo-irreversible acetylcholinesterase inhibitors by means of an immobilized enzyme reactor.
2007 Mar 9
Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens.
2008 Aug
Preoperative steroid therapy stabilizes postoperative respiratory conditions in myasthenia gravis.
2008 Mar
Preoperative steroid therapy stabilizes postoperative respiratory condition in myasthenia gravis.
2008 Mar
AChR deficiency due to epsilon-subunit mutations: two common mutations in the Netherlands.
2009 Oct
Patents

Patents

Sample Use Guides

For the patient with moderately severe myasthenia, from 5 mg to 25 mg of MYTELASE three or four times daily is an effective dose. In some patients a 5 mg dose is effective, whereas other patients require as much as from 50 mg to 75 mg per dose. The physician should start with a 5 mg dose, carefully observing the effect of the drug on the patient. The dosage may then be increased gradually to determine the effective and safe dose.
Route of Administration: Oral
In Vitro Use Guide
Inhibitory constant of ambenonium to bovine erythrocyte AChE determined in vitro was 3.7 nM.
Name Type Language
AMBENONIUM
VANDF   WHO-DD  
Common Name English
BENZENEMETHANAMINIUM, N,N'-((1,2-DIOXO-1,2-ETHANEDIYL)BIS(IMINO-2,1-ETHANEDIYL))BIS(2-CHLORO-N',N'-DIETHYL-
Common Name English
OXALYLBIS(IMINOETHYLENE))BIS((O-CHLOROBENZYL)DIETHYLAMMONIUM
Common Name English
AMBENONIUM ION
Common Name English
AMBENONIUM CATION
Common Name English
AMBENONIUM [WHO-DD]
Common Name English
AMBENONIUM [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000177
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
WHO-ATC N07AA30
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
NDF-RT N0000175723
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
LIVERTOX 34
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
NCI_THESAURUS C47792
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
WHO-VATC QN07AA30
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
Code System Code Type Description
CAS
7648-98-8
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY
DRUG CENTRAL
146
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY
EPA CompTox
7648-98-8
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY
RXCUI
623
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C76136
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY
DRUG BANK
DB01122
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY
EVMPD
SUB00425MIG
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY
PUBCHEM
2131
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY
FDA UNII
L16PUN799N
Created by admin on Sat Jun 26 06:33:55 UTC 2021 , Edited by admin on Sat Jun 26 06:33:55 UTC 2021
PRIMARY