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Details

Stereochemistry ACHIRAL
Molecular Formula C9H13N2O2.Cl
Molecular Weight 216.665
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PYRIDOSTIGMINE CHLORIDE

SMILES

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

InChI

InChIKey=TYXYRYORUZYJDX-UHFFFAOYSA-M
InChI=1S/C9H13N2O2.ClH/c1-10(2)9(12)13-8-5-4-6-11(3)7-8;/h4-7H,1-3H3;1H/q+1;/p-1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21815707

Acquired myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction, characterized clinically by muscle weakness and abnormal fatigability on exertion. Current guidelines and recommendations for MG treatment are based largely on clinical experience, retrospective analyses and expert consensus. Pyridostigmine (under the trade names Mestinon (Valeant Pharmaceuticals)), has been used as a treatment for MG for over 50 years and is generally considered safe. It is suitable as a long-term treatment in patients with generalized non-progressive milder disease, and as an adjunctive therapy in patients with severe disease who are also receiving immunotherapy. Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft by competing with acetylcholine for attachment to acetylcholinesterase, thus slowing down the hydrolysis of acetylcholine, and thereby increases efficiency of cholinergic transmission in the neuromuscular junction and prolongs the effects of acetylcholine. The side effects of Mestinon are most commonly related to over dosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis. Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Muscarinic side effects can usually be counteracted by atropine, but for reasons shown in the preceding section the expedient is not without danger. As with any compound containing the bromide radical, a skin rash may be seen in an occasional patient. Such reactions usually subside promptly upon discontinuance of the medication.

CNS Activity

Curator's Comment: Known to be CNS penetrant in mouse. Human data not available

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MESTINON

Approved Use

Pyridostigmine bromide is useful in the treatment of myasthenia gravis.

Launch Date

1955
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
176.03 ng/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PYRIDOSTIGMINE BROMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
819.999 ng × h/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PYRIDOSTIGMINE BROMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
909.86 ng × h/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PYRIDOSTIGMINE BROMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.787 h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PYRIDOSTIGMINE BROMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
18.8%
single, unknown
PYRIDOSTIGMINE BROMIDE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
180 mg 3 times / day multiple, oral
MTD
Dose: 180 mg, 3 times / day
Route: oral
Route: multiple
Dose: 180 mg, 3 times / day
Sources:
unhealthy, 18-67 years
n = 10
Health Status: unhealthy
Condition: autonomic neuropathy | constipation
Age Group: 18-67 years
Sex: M+F
Population Size: 10
Sources:
160 mg 3 times / day multiple, oral
Studied dose
Dose: 160 mg, 3 times / day
Route: oral
Route: multiple
Dose: 160 mg, 3 times / day
Sources:
unhealthy, 18-67 years
n = 10
Health Status: unhealthy
Condition: autonomic neuropathy | constipation
Age Group: 18-67 years
Sex: M+F
Population Size: 10
Sources:
DLT: Diaphoresis, Sweating...
Dose limiting toxicities:
Diaphoresis (10%)
Sweating (10%)
Abdominal cramps (10%)
Sources:
30 mg 3 times / day multiple, oral
Recommended
Dose: 30 mg, 3 times / day
Route: oral
Route: multiple
Dose: 30 mg, 3 times / day
Sources:
healthy, adult
n = 41650
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 41650
Sources:
Disc. AE: Headache, Hypertension...
AEs leading to
discontinuation/dose reduction:
Headache (0.002%)
Hypertension (0.005%)
Allergic reaction (0.005%)
Bronchitis (0.007%)
Nausea (0.05%)
Diarrhea (0.05%)
Sources:
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Other AEs: Abdominal cramps, Diarrhea...
Other AEs:
Abdominal cramps
Diarrhea
Emesis
Nausea
Hypersalivation
Urinary incontinence
Muscle weakness
Blurred vision
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal cramps 10%
DLT
160 mg 3 times / day multiple, oral
Studied dose
Dose: 160 mg, 3 times / day
Route: oral
Route: multiple
Dose: 160 mg, 3 times / day
Sources:
unhealthy, 18-67 years
n = 10
Health Status: unhealthy
Condition: autonomic neuropathy | constipation
Age Group: 18-67 years
Sex: M+F
Population Size: 10
Sources:
Diaphoresis 10%
DLT
160 mg 3 times / day multiple, oral
Studied dose
Dose: 160 mg, 3 times / day
Route: oral
Route: multiple
Dose: 160 mg, 3 times / day
Sources:
unhealthy, 18-67 years
n = 10
Health Status: unhealthy
Condition: autonomic neuropathy | constipation
Age Group: 18-67 years
Sex: M+F
Population Size: 10
Sources:
Sweating 10%
DLT
160 mg 3 times / day multiple, oral
Studied dose
Dose: 160 mg, 3 times / day
Route: oral
Route: multiple
Dose: 160 mg, 3 times / day
Sources:
unhealthy, 18-67 years
n = 10
Health Status: unhealthy
Condition: autonomic neuropathy | constipation
Age Group: 18-67 years
Sex: M+F
Population Size: 10
Sources:
Headache 0.002%
Disc. AE
30 mg 3 times / day multiple, oral
Recommended
Dose: 30 mg, 3 times / day
Route: oral
Route: multiple
Dose: 30 mg, 3 times / day
Sources:
healthy, adult
n = 41650
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 41650
Sources:
Allergic reaction 0.005%
Disc. AE
30 mg 3 times / day multiple, oral
Recommended
Dose: 30 mg, 3 times / day
Route: oral
Route: multiple
Dose: 30 mg, 3 times / day
Sources:
healthy, adult
n = 41650
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 41650
Sources:
Hypertension 0.005%
Disc. AE
30 mg 3 times / day multiple, oral
Recommended
Dose: 30 mg, 3 times / day
Route: oral
Route: multiple
Dose: 30 mg, 3 times / day
Sources:
healthy, adult
n = 41650
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 41650
Sources:
Bronchitis 0.007%
Disc. AE
30 mg 3 times / day multiple, oral
Recommended
Dose: 30 mg, 3 times / day
Route: oral
Route: multiple
Dose: 30 mg, 3 times / day
Sources:
healthy, adult
n = 41650
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 41650
Sources:
Diarrhea 0.05%
Disc. AE
30 mg 3 times / day multiple, oral
Recommended
Dose: 30 mg, 3 times / day
Route: oral
Route: multiple
Dose: 30 mg, 3 times / day
Sources:
healthy, adult
n = 41650
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 41650
Sources:
Nausea 0.05%
Disc. AE
30 mg 3 times / day multiple, oral
Recommended
Dose: 30 mg, 3 times / day
Route: oral
Route: multiple
Dose: 30 mg, 3 times / day
Sources:
healthy, adult
n = 41650
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 41650
Sources:
Abdominal cramps
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Blurred vision
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Diarrhea
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Emesis
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Hypersalivation
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Muscle weakness
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Nausea
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
Urinary incontinence
900 mg 1 times / day single, oral
Studied dose
Dose: 900 mg, 1 times / day
Route: oral
Route: single
Dose: 900 mg, 1 times / day
Sources:
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 1
Sources:
PubMed

PubMed

TitleDatePubMed
Neurotoxicology of the brain barrier system: new implications.
2001
[Myasthenia gravis associated with HIV infection].
2001
Familial autoimmune myasthenia gravis.
2001 Apr
Combined exposure to sarin and pyridostigmine bromide increased levels of rat urinary 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanosine, biomarkers of oxidative stress.
2001 Aug 6
Bretazenil, a benzodiazepine receptor partial agonist, as an adjunct in the prophylactic treatment of OP poisoning.
2001 Dec
Intramuscular diazepam pharmacokinetics in soman-exposed guinea pigs.
2001 Dec
Combination anticonvulsant treatment of soman-induced seizures.
2001 Dec
The effect of continuous pyridostigmine administration on functional (A12) acetylcholinesterase activity in guinea-pig muscles.
2001 Dec
Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans.
2001 Dec
Effects of contralateral white noise stimulation on distortion product otoacoustic emissions in myasthenic patients.
2001 Dec
A validated HPLC method for the determination of pyridostigmine bromide, acetaminophen, acetylsalicylic acid and caffeine in rat plasma and urine.
2001 Dec
Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects.
2001 Feb
Many Gulf War illnesses may be autoimmune disorders caused by the chemical and biological stressors pyridostigmine bromide, and adrenaline.
2001 Feb
Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C.
2001 Jul
High-performance liquid chromatographic determination of pyridostigmine bromide, nicotine, and their metabolites in rat plasma and urine.
2001 Jul
Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice.
2001 Jul-Aug
Involvement of the cholinergic pathway in the pathogenesis of pituitary Cushing's syndrome.
2001 Jun
Pyridostigmine-induced microcephaly.
2001 Jun 12
Myasthenia gravis with autoimmune autonomic neuropathy.
2001 May 14
The effects of pyridostigmine bromide, permethrin, and DEET alone, or in combination, on fixed-ratio and fixed-interval behavior in male and female rats.
2001 May-Jun
Long-term evaluation of extended thymectomy with anterior mediastinal dissection for myasthenia gravis.
2001 Oct
Peri-operative management of patients for video assisted thoracoscopic thymectomy in myasthenia gravis.
2001 Oct-Dec
Minimal change nephrotic syndrome associated with malignant thymoma: case report and literature review.
2001 Sep
Myasthenia gravis in children: analysis of 18 patients.
2001 Sep
Electroplegia: an alternative to blood cardioplegia for arresting the heart during conventional (on-pump) cardiac operation.
2001 Sep
Effects of melatonin on fuel utilization in exercised rats: role of nitric oxide and growth hormone.
2001 Sep
The use of carbamates, atropine, and 2-pyridine aldoxime methoiodide in the protection of Artemia salina against poisoning by carbophenothion.
2001 Sep
Determination of depleted uranium, pyridostigmine bromide and its metabolite in plasma and urine following combined administration in rats.
2001 Sep
Major review: the clinical spectrum of pediatric myasthenia gravis: blepharoptosis, ophthalmoplegia and strabismus. A report of 14 cases.
2002
Subchronic administration of pyridostigmine or huperzine to primates: compared efficacy against soman toxicity.
2002 Aug
A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice.
2002 Aug 15
Myasthenia gravis in pregnancy: report on 69 cases.
2002 Aug 5
B Cell lymphoma of the brain stem masquerading as myasthenia.
2002 Feb
Peripheral cholinergic pathway modulates hyperthermia induced by stress in rats exposed to open-field stress.
2002 Feb
Pyridophens: binary pyridostigmine-aprophen prodrugs with differential inhibition of acetylcholinesterase, butyrylcholinesterase, and muscarinic receptors.
2002 Feb 14
The use of the pyridostigmine growth hormone-releasing hormone stimulation test to detect growth hormone deficiency in patients with pituitary adenomas.
2002 Jan
Prevention and treatment of injury from chemical warfare agents.
2002 Jan 7
Ocular myasthenia presenting as progressive external ophthalmoplegia.
2002 Jan-Feb
Neither forced running nor forced swimming affect acute pyridostigmine toxicity or brain-regional cholinesterase inhibition in rats.
2002 Jul 1
Cardiorespiratory effects following acute exposure to pyridostigmine bromide and/or N,N-diethyl-m-toluamide (DEET) in rats.
2002 Jul-Aug
Pyridostigmine bromide and the long-term subjective health status of a sample of over 700 male Reserve Component Gulf War era veterans.
2002 Jun
Cholinergic stimulation with pyridostigmine reduces the QTc interval in coronary artery disease.
2002 Jun
[Growth disorders in Down's syndrome: growth hormone treatment].
2002 Jun
Risk factors for multisymptom illness in US Army veterans of the Gulf War.
2002 Mar
Caramiphen and scopolamine prevent soman-induced brain damage and cognitive dysfunction.
2002 May
Review of the value of huperzine as pretreatment of organophosphate poisoning.
2002 May
Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin.
2002 May
[Myasthenia gravis in infancy. A report of 12 cases].
2002 May 16-31
Idiotypic mimicry of a catalytic antibody active site.
2002 Oct
Pharmacokinetic/pharmacodynamic modeling of rocuronium in myasthenic patients is improved by taking into account the number of unbound acetylcholine receptors.
2002 Sep
Patents

Sample Use Guides

Syrup: This form permits accurate dosage adjustment for children and "brittle" myasthenic patients who require fractions of 60 mg doses. It is more easily swallowed, especially in the morning, by patients with bulbar involvement. Timespan Tablets: This form provides uniformly slow release, hence prolonged duration of drug action; it facilitates control of myasthenic symptoms with fewer individual doses daily. The immediate effect of a 180 mg Timespan Tablet is about equal to that of a 60 mg Conventional Tablet; however, its duration of effectiveness, although varying in individual patients, averages 2½ times that of a 60 mg dose.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: The objective of this study was to investigate the effect of Mestinon (Pyridostigmin) on platelet aggregation stimulated with various agonists in vitro. The results showed that in the presence of pyridostigmine, platelet aggregation was inhibited in response to ADP and collagen stimulations. However, when agonists such as ristocetin and arachidonic acid were used, aggregation of platelets was detectable even though the degree of aggregation was relatively reduced when compared with control samples. Pyridostigmine interferes with human platelet aggregation and uncommonly in susceptible patient may result in bleeding tendency.
Unknown
Name Type Language
PYRIDOSTIGMINE CHLORIDE
Common Name English
PYRIDINIUM, 3-(((DIMETHYLAMINO)CARBONYL)OXY)-1-METHYL-, CHLORIDE (1:1)
Systematic Name English
Code System Code Type Description
FDA UNII
45X1P9AO69
Created by admin on Fri Dec 15 15:17:25 GMT 2023 , Edited by admin on Fri Dec 15 15:17:25 GMT 2023
PRIMARY
EPA CompTox
DTXSID90998129
Created by admin on Fri Dec 15 15:17:25 GMT 2023 , Edited by admin on Fri Dec 15 15:17:25 GMT 2023
PRIMARY
PUBCHEM
202190
Created by admin on Fri Dec 15 15:17:25 GMT 2023 , Edited by admin on Fri Dec 15 15:17:25 GMT 2023
PRIMARY
CAS
7681-22-3
Created by admin on Fri Dec 15 15:17:25 GMT 2023 , Edited by admin on Fri Dec 15 15:17:25 GMT 2023
PRIMARY
DRUG BANK
DBSALT002338
Created by admin on Fri Dec 15 15:17:25 GMT 2023 , Edited by admin on Fri Dec 15 15:17:25 GMT 2023
PRIMARY