U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C9H13N2O2
Molecular Weight 181.2121
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 1

SHOW SMILES / InChI
Structure of PYRIDOSTIGMINE

SMILES

CN(C)C(=O)Oc1ccc[n+](C)c1

InChI

InChIKey=RVOLLAQWKVFTGE-UHFFFAOYSA-N
InChI=1S/C9H13N2O2/c1-10(2)9(12)13-8-5-4-6-11(3)7-8/h4-7H,1-3H3/q+1

HIDE SMILES / InChI

Description
Curator's Comment:: 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

-465177600000
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
Health Status: unhealthy
Age Group: 18-67 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 18-67 years
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: unhealthy
Age Group: 18-67 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 18-67 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 18-67 years
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M+F
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: healthy
Age Group: adult
Sex: M
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
Health Status: healthy
Age Group: adult
Sex: M
Sources:
PubMed

PubMed

TitleDatePubMed
Neurotoxicology of the brain barrier system: new implications.
2001
[Myasthenia gravis associated with HIV infection].
2001
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
Beneficial effects of TCP on soman intoxication in guinea pigs: seizures, brain damage and learning behaviour.
2001 Dec
Insulin-like growth factor-I restores the reduced somatostatinergic tone controlling growth hormone secretion in cirrhotic rats.
2001 Dec
The effect of continuous pyridostigmine administration on functional (A12) acetylcholinesterase activity in guinea-pig muscles.
2001 Dec
Effects of contralateral white noise stimulation on distortion product otoacoustic emissions in myasthenic patients.
2001 Dec
Laryngeal myasthenia gravis: report of 40 cases.
2001 Mar
Central nervous system effects from a peripherally acting cholinesterase inhibiting agent: interaction with stress or genetics.
2001 Mar
Peri-operative management of patients for video assisted thoracoscopic thymectomy in myasthenia gravis.
2001 Oct-Dec
The combined effects of pyridostigmine and chronic stress on brain cortical and blood acetylcholinesterase, corticosterone, prolactin and alternation performance in rats.
2001 Oct-Nov
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
Major review: the clinical spectrum of pediatric myasthenia gravis: blepharoptosis, ophthalmoplegia and strabismus. A report of 14 cases.
2002
Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome.
2002 Aug
Altered hypothalamic cholinergic responses in patients with nonulcer dyspepsia: a study of pyridostigmine-stimulated growth hormone release.
2002 Aug
Pharmacological antagonism of lethal effects induced by O-isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate.
2002 Aug
Subchronic administration of pyridostigmine or huperzine to primates: compared efficacy against soman toxicity.
2002 Aug
Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin. Alone and in combination.
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
Preparation and in vitro evaluation of pyridostigmine bromide microparticles.
2002 Aug 21
Myasthenia gravis in pregnancy: report on 69 cases.
2002 Aug 5
Poor ovarian response to gonadotrophin stimulation the role of adjuvant treatments.
2002 Feb
The Department of Defense's Persian Gulf War registry year 2000: an examination of veterans' health status.
2002 Feb
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
Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis.
2002 Jul
Sensitivity to vecuronium in seropositive and seronegative patients with myasthenia gravis.
2002 Jul
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
[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
Sensorimotor deficit and cholinergic changes following coexposure with pyridostigmine bromide and sarin in rats.
2002 Mar
In vitro human metabolism and interactions of repellent N,N-diethyl-m-toluamide.
2002 Mar
Impaired growth hormone secretion in fibromyalgia patients: evidence for augmented hypothalamic somatostatin tone.
2002 May
Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin.
2002 May
Actions of pyridostigmine and organophosphate agents on chick cells, mice, and chickens.
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
In myasthenia gravis, clinical and immunological improvement post-thymectomy segregate with results of in vitro antibody secretion by immunocytes.
2002 Oct 15
Acute and repeated restraint stress have little effect on pyridostigmine toxicity or brain regional cholinesterase inhibition in rats.
2002 Sep
Complete inhibition of hypothalamic somatostatin activity is only partially responsible for the growth hormone response to strenuous exercise.
2002 Sep
Pharmacokinetic/pharmacodynamic modeling of rocuronium in myasthenic patients is improved by taking into account the number of unbound acetylcholine receptors.
2002 Sep
Gulf War related exposure factors influencing topical absorption of 14C-permethrin.
2002 Sep 5
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.
Route of Administration: Oral
Name Type Language
PYRIDOSTIGMINE
VANDF   WHO-DD  
Common Name English
PYRIDOSTIGMINE [WHO-DD]
Common Name English
3-((DIMETHYLCARBAMOYL)OXY)-1-METHYLPYRIDINIUM
Systematic Name English
PYRIDINIUM, 3-(((DIMETHYLAMINO)CARBONYL)OXY)-1-METHYL-
Systematic Name English
PYRIDOSTIGMINE CATION
Common Name English
PYRIDOSTIGMINE ION
Common Name English
PYRIDOSTIGMINE [VANDF]
Common Name English
Classification Tree Code System Code
WHO-ATC N07AA02
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 20
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
WHO-VATC QN07AA02
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
NDF-RT N0000175723
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
LIVERTOX 818
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
NCI_THESAURUS C47792
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
NDF-RT N0000000177
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
Code System Code Type Description
CAS
155-97-5
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
LACTMED
Pyridostigmine
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
DRUG BANK
DB00545
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
EPA CompTox
155-97-5
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
WIKIPEDIA
PYRIDOSTIGMINE
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
NCI_THESAURUS
C76139
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
PUBCHEM
4991
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
FDA UNII
19QM69HH21
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
EVMPD
SUB15059MIG
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
DRUG CENTRAL
2330
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY
RXCUI
9000
Created by admin on Sat Jun 26 03:47:51 UTC 2021 , Edited by admin on Sat Jun 26 03:47:51 UTC 2021
PRIMARY RxNorm