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
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
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 Date1955 |
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 |
---|---|---|
Neurotoxicology of the brain barrier system: new implications. | 2001 |
|
Familial autoimmune myasthenia gravis. | 2001 Apr |
|
Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience. | 2001 Apr |
|
Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination. | 2001 Apr |
|
Intramuscular diazepam pharmacokinetics in soman-exposed guinea pigs. | 2001 Dec |
|
Insulin-like growth factor-I restores the reduced somatostatinergic tone controlling growth hormone secretion in cirrhotic rats. | 2001 Dec |
|
Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans. | 2001 Dec |
|
Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition. | 2001 Dec |
|
Many Gulf War illnesses may be autoimmune disorders caused by the chemical and biological stressors pyridostigmine bromide, and adrenaline. | 2001 Feb |
|
Bulbar presentations of myasthenia gravis in the elderly patient. | 2001 Jan |
|
Viral neuroinvasion as a marker for BBB integrity following exposure to cholinesterase inhibitors. | 2001 Jan 19 |
|
Involvement of the cholinergic pathway in the pathogenesis of pituitary Cushing's syndrome. | 2001 Jun |
|
Central nervous system effects from a peripherally acting cholinesterase inhibiting agent: interaction with stress or genetics. | 2001 Mar |
|
Subchronic administration of various pretreatments of nerve agent poisoning. I. Protection of blood and central cholinesterases, innocuousness towards blood-brain barrier permeability. | 2001 May |
|
Effects of melatonin on fuel utilization in exercised rats: role of nitric oxide and growth hormone. | 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 |
|
Poor ovarian response to gonadotrophin stimulation the role of adjuvant treatments. | 2002 Feb |
|
Prevention and treatment of injury from chemical warfare agents. | 2002 Jan 7 |
|
Sensitivity to vecuronium in seropositive and seronegative patients with myasthenia gravis. | 2002 Jul |
|
Pyridostigmine bromide and the long-term subjective health status of a sample of over 700 male Reserve Component Gulf War era veterans. | 2002 Jun |
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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45X1P9AO69
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DTXSID90998129
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202190
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7681-22-3
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DBSALT002338
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ACTIVE MOIETY
SUBSTANCE RECORD