Details
Stereochemistry | ACHIRAL |
Molecular Formula | C9H13N2O2 |
Molecular Weight | 181.2117 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 1 |
SHOW SMILES / InChI
SMILES
CN(C)C(=O)OC1=C[N+](C)=CC=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
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21815707
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10814558 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | MESTINON Approved UsePyridostigmine bromide is useful in the treatment of myasthenia gravis. Launch Date-4.65177608E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
18.8% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12029383 |
single, unknown |
PYRIDOSTIGMINE BROMIDE unknown | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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%) Sources: Sweating (10%) Abdominal cramps (10%) |
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%) Sources: Hypertension (0.005%) Allergic reaction (0.005%) Bronchitis (0.007%) Nausea (0.05%) Diarrhea (0.05%) |
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 Sources: Diarrhea Emesis Nausea Hypersalivation Urinary incontinence Muscle weakness Blurred vision |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/12642463/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no |
PubMed
Title | Date | PubMed |
---|---|---|
Prognostic factors of thymectomy in patients with myasthenia gravis: a cohort of 132 patients. | 2001 |
|
[Myasthenia gravis associated with HIV infection]. | 2001 |
|
Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine. | 2001 Apr |
|
Development of a high-performance liquid chromatographic method for the quantification of chlorpyrifos, pyridostigmine bromide, N,N-diethyl-m-toluamide and their metabolites in rat plasma and urine. | 2001 Apr 25 |
|
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 |
|
Combination anticonvulsant treatment of soman-induced seizures. | 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 |
|
The role of cholinergic transmission in outer hair cell functioning evaluated by distortion product otoacoustic emissions in myasthenic patients. | 2001 Jan |
|
Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C. | 2001 Jul |
|
Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice. | 2001 Jul-Aug |
|
Central nervous system effects from a peripherally acting cholinesterase inhibiting agent: interaction with stress or genetics. | 2001 Mar |
|
Myasthenia gravis with autoimmune autonomic neuropathy. | 2001 May 14 |
|
The use of intravenous immunoglobulin as maintenance therapy in myasthenia gravis. | 2001 May-Jun |
|
Fetal antigen 1 in healthy adults and patients with pituitary disease: relation to physiological, pathological, and pharmacological GH levels. | 2001 Nov |
|
Long-term evaluation of extended thymectomy with anterior mediastinal dissection for myasthenia gravis. | 2001 Oct |
|
The combined effects of pyridostigmine and chronic stress on brain cortical and blood acetylcholinesterase, corticosterone, prolactin and alternation performance in rats. | 2001 Oct-Nov |
|
Myasthenia gravis in children: analysis of 18 patients. | 2001 Sep |
|
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 |
|
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 |
|
[Growth disorders in Down's syndrome: growth hormone treatment]. | 2002 Jun |
|
Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa. | 2002 Mar |
|
Risk factors for multisymptom illness in US Army veterans of the Gulf War. | 2002 Mar |
|
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 |
|
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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19694313
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
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Classification Tree | Code System | Code | ||
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WHO-ATC |
N07AA02
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WHO-ESSENTIAL MEDICINES LIST |
20
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WHO-VATC |
QN07AA02
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NDF-RT |
N0000175723
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LIVERTOX |
818
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NCI_THESAURUS |
C47792
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NDF-RT |
N0000000177
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Code System | Code | Type | Description | ||
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155-97-5
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Pyridostigmine
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DB00545
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DTXSID20165786
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PYRIDOSTIGMINE
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C76139
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4991
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19QM69HH21
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SUB15059MIG
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2330
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19QM69HH21
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9000
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PRIMARY | RxNorm |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)