Identification

Name
Pyridostigmine
Accession Number
DB00545  (APRD00380)
Type
Small Molecule
Groups
Approved, Investigational
Description

A cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.

Structure
Thumb
Synonyms
  • Pyridostigmine cation
Product Ingredients
IngredientUNIICASInChI Key
Pyridostigmine bromideKVI301NA53101-26-8VNYBTNPBYXSMOO-UHFFFAOYSA-M
Pyridostigmine chloride45X1P9AO697681-22-3TYXYRYORUZYJDX-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MestinonSyrup60 mg/5mLOralValeant Pharmaceuticals North America1965-01-25Not applicableUs
MestinonTablet, extended release180 mg/1OralValeant Pharmaceuticals North America1959-01-12Not applicableUs
MestinonTablet60 mg/1OralValeant Pharmaceuticals North America1955-04-06Not applicableUs
Mestinon Tab 60mg USPTablet60 mgOralValeant Canada Lp Valeant Canada S.E.C.1990-12-31Not applicableCanada
Mestinon-SRTablet, extended release180 mgOralValeant Canada Lp Valeant Canada S.E.C.1991-12-31Not applicableCanada
Pyridostigmine bromideTablet30 mg/1OralValeant Pharmaceuticals2008-10-27Not applicableUs
RegonolInjection, solution5 mg/1mLIntravenous; ParenteralSandoz2005-05-10Not applicableUs
Regonol Inj 5mg/mlLiquid5 mgIntramuscular; IntravenousOrganon Canada Ltd Ltee1977-12-311999-08-11Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pyridostigmine BromideTablet60 mg/1OralCadila Pharnmaceuticals2015-08-07Not applicableUs
Pyridostigmine BromideTablet60 mg/1OralKaiser Foundations Hospitals2010-08-022012-07-31Us
Pyridostigmine BromideTablet60 mg/1OralSandoz2003-01-072013-02-28Us
Pyridostigmine BromideTablet60 mg/1Oralbryant ranch prepack2015-08-07Not applicableUs
Pyridostigmine BromideTablet, extended release180 mg/1OralOceanside Pharmaceuticals1959-01-12Not applicableUs
Pyridostigmine BromideTablet60 mg/1OralImpax Generics2003-04-24Not applicableUs0115 351120180907 15195 mydvku
Pyridostigmine BromideTablet, extended release180 mg/1OralImpax Generics2015-09-18Not applicableUs
Pyridostigmine BromideTablet, extended release180 mg/1OralAlvogen, Inc.2015-06-29Not applicableUs
Pyridostigmine BromideTablet60 mg/1OralOceanside Pharmaceuticals2007-10-30Not applicableUs
Pyridostigmine BromideTablet60 mg/1OralZydus Pharmaceuticals Usa, Inc.2015-08-07Not applicableUs
International/Other Brands
Amiasten (AC Farma) / Amygra (Tabros) / Antilon (Yuan Chou) / Astinon (Samarth) / Kalymin (Arzneimittelwerk Dresden) / Kalymin forte (Temmler) / Kalymin N (Temmler) / Kalymin retard (Temmler) / Meshanon60 (Hasan) / Mestinon / Mestinon retard (Meda) / Myestin (VHB) / Pyrimine (Sriprasit Dispensary) / Regonol
Categories
UNII
19QM69HH21
CAS number
155-97-5
Weight
Average: 181.2117
Monoisotopic: 181.09770267
Chemical Formula
C9H13N2O2
InChI Key
RVOLLAQWKVFTGE-UHFFFAOYSA-N
InChI
InChI=1S/C9H13N2O2/c1-10(2)9(12)13-8-5-4-6-11(3)7-8/h4-7H,1-3H3/q+1
IUPAC Name
3-[(dimethylcarbamoyl)oxy]-1-methylpyridin-1-ium
SMILES
CN(C)C(=O)OC1=C[N+](C)=CC=C1

Pharmacology

Indication

For the treatment of myasthenia gravis.

Associated Conditions
Pharmacodynamics

Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and doesn't cross the blood-brain barrier. Pyridostigmine has a slightly longer duration of action than NEOSTIGMINE. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.

Mechanism of action

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 prolonges the effects of acetylcholine.

TargetActionsOrganism
AAcetylcholinesterase
antagonist
inhibitor
Human
ACholinesterase
antagonist
Human
USerum albuminNot AvailableHuman
Absorption

Poorly absorbed from the GI tract with an oral bioavailability of 7.6 +/- 2.4%.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hydrolysis by cholinesterases and by liver.

Route of elimination
Not Available
Half life

3 hours following oral administration.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe therapeutic efficacy of (2-benzhydryloxyethyl)diethyl-methylammonium iodide can be decreased when used in combination with Pyridostigmine.
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Pyridostigmine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Pyridostigmine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Pyridostigmine.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Pyridostigmine.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Pyridostigmine.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Pyridostigmine.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Pyridostigmine.
AcebutololPyridostigmine may increase the bradycardic activities of Acebutolol.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Pyridostigmine.
Food Interactions
  • Take with food to decrease adverse effects.

References

Synthesis Reference

Thomas Zich, "Preparation of substituted pyridine N-oxide compounds." U.S. Patent US20040063957, issued April 01, 2004.

US20040063957
General References
  1. Singer W, Opfer-Gehrking TL, McPhee BR, Hilz MJ, Bharucha AE, Low PA: Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension. J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1294-8. [PubMed:12933939]
External Links
Human Metabolome Database
HMDB0014685
KEGG Drug
D00487
KEGG Compound
C07410
PubChem Compound
4991
PubChem Substance
46506129
ChemSpider
4817
BindingDB
50313079
ChEBI
8665
ChEMBL
CHEMBL1115
Therapeutic Targets Database
DNC001171
PharmGKB
PA451185
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pyridostigmine
ATC Codes
N07AA02 — Pyridostigmine
AHFS Codes
  • 12:04.00 — Parasympathomemetic (Cholinergic) Agents
FDA label
Download (120 KB)
MSDS
Download (74.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
0RecruitingDiagnosticOrthostatic Intolerance / Postural Orthostatic Tachycardia Syndrome (POTS) / POTS1
0TerminatedTreatmentPompe's Disease1
1CompletedNot AvailableAutonomic Failure / Idiopathic orthostatic hypotension1
1RecruitingBasic ScienceDiabetes Mellitus (DM)1
1RecruitingBasic SciencePostural Tachycardia Syndrome1
1, 2CompletedTreatmentColonic Transit / Diabetes Mellitus (DM) / Gastric Emptying / Occasional Constipation1
2Active Not RecruitingTreatmentAutonomic Disturbances in Parkinson's Disease1
2Active Not RecruitingTreatmentCD4+ T Lymphocytopenia / HIV-1-infection / Immune Deficiencies / Immuno-senescence1
2CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentFibromyalgia1
2CompletedTreatmentHeart Failure, Unspecified1
2CompletedTreatmentKugelberg-Welander Disease / SMA / Spinal Muscular Atrophy (SMA)1
2CompletedTreatmentIdiopathic orthostatic hypotension1
2RecruitingTreatmentAutonomic Dysreflexia / Autonomic Integrity / Baroreceptor Integrity / Blood Pressures / Cerebral Blood Flow / Cognitive Function / Hypotensive / Spinal Cord Injuries (SCI) / Sympathetic Integrity / Vagal Integrity1
2RecruitingTreatmentSpinal Muscular Atrophy Type 31
2RecruitingTreatmentIdiopathic orthostatic hypotension1
3CompletedTreatmentLeukemias1
3Not Yet RecruitingTreatmentDyspnea / Fibromyalgia / Myalgic Encephalomyelitis (ME) / Preload Failure1
3TerminatedTreatmentOcular Myasthenia Gravis1
4Active Not RecruitingSupportive CareMuscle Relaxation1
4CompletedTreatmentPostural Orthostatic Tachycardia Syndrome (POTS)1
4RecruitingTreatmentMyasthenia Gravis1
4RecruitingTreatmentOrthostatic; Hypotension, Neurogenic1
Not AvailableCompletedTreatmentDiabetes Complications1
Not AvailableRecruitingTreatmentPostural Tachycardia Syndrome1

Pharmacoeconomics

Manufacturers
  • Valeant pharmaceuticals international
  • Sandoz canada inc
  • Barr laboratories inc
  • Corepharma llc
  • Impax laboratories inc
  • Solvay pharmaceuticals
  • United states army office surgeon general
Packagers
  • Barr Pharmaceuticals
  • Corepharma LLC
  • DSM Corp.
  • Global Pharmaceuticals
  • Heartland Repack Services LLC
  • Impax Laboratories Inc.
  • Kaiser Foundation Hospital
  • Legacy Pharmaceuticals Packaging LLC
  • Murfreesboro Pharmaceutical Nursing Supply
  • Oceanside Pharmaceuticals Incorporated
  • Professional Co.
  • Sandoz
  • Southcoast Pharmaceuticals Inc.
  • Valeant Ltd.
Dosage forms
FormRouteStrength
SyrupOral60 mg/5mL
TabletOral60 mg
Tablet, extended releaseOral180 mg
TabletOral180 mg/1
TabletOral30 mg/1
TabletOral60 mg/1
Tablet, extended releaseOral180 mg/1
Injection, solutionIntravenous; Parenteral5 mg/1mL
LiquidIntramuscular; Intravenous5 mg
Prices
Unit descriptionCostUnit
Mestinon 30 180 mg Controlled Release Tabs Bottle129.42USD bottle
Pyridostigmine bromide powder87.6USD g
Regonol 5 mg/ml ampul13.64USD ml
Mestinon 180 mg timespan3.59USD each
Mestinon 60 mg tablet2.46USD tablet
Mestinon-Sr 180 mg Sustained-Release Tablet1.06USD tablet
Pyridostigmine Bromide 60 mg tablet0.62USD tablet
Pyridostigmine br 60 mg tablet0.6USD tablet
Mestinon 60 mg Tablet0.48USD tablet
Mestinon 60 mg/5ml Syrup0.43USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)153 °CNot Available
logP1.554Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.04 mg/mLALOGPS
logP-3.1ALOGPS
logP-3.5ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)19.53ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area33.42 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity49.66 m3·mol-1ChemAxon
Polarizability19.38 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9441
Blood Brain Barrier+0.9818
Caco-2 permeable+0.6465
P-glycoprotein substrateNon-substrate0.737
P-glycoprotein inhibitor INon-inhibitor0.915
P-glycoprotein inhibitor IINon-inhibitor0.8654
Renal organic cation transporterNon-inhibitor0.8863
CYP450 2C9 substrateNon-substrate0.7541
CYP450 2D6 substrateNon-substrate0.7082
CYP450 3A4 substrateSubstrate0.586
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9341
CYP450 2D6 inhibitorNon-inhibitor0.9274
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9782
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8422
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9193
BiodegradationReady biodegradable0.5528
Rat acute toxicity3.1468 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9248
hERG inhibition (predictor II)Non-inhibitor0.8484
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-methylpyridinium compounds. These are methylpyridines that carry a methyl group at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Methylpyridines
Direct Parent
N-methylpyridinium compounds
Alternative Parents
Pyridinium derivatives / Heteroaromatic compounds / Carbamate esters / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
show 1 more
Substituents
N-methylpyridinium / Pyridinium / Carbamic acid ester / Heteroaromatic compound / Carbonic acid derivative / Azacycle / Organic oxide / Organopnictogen compound / Organic oxygen compound / Organooxygen compound
show 6 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyridinium ion (CHEBI:8665)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Drake-Baumann R, Seil FJ: Effects of exposure to low-dose pyridostigmine on neuromuscular junctions in vitro. Muscle Nerve. 1999 Jun;22(6):696-703. [PubMed:10366222]
  2. Ricordel I, Meunier J: [Chemical weapons: antidotes. View about the real means, perspectives]. Ann Pharm Fr. 2000 Jan;58(1):5-12. [PubMed:10669805]
  3. Prasad V, Scotch R, Chaudhuri AR, Walss C, Fathy DB, Miller C, Luduena RF: Interactions of bovine brain tubulin with pyridostigmine bromide and N,N'-diethyl-m-toluamide. Neurochem Res. 2000 Jan;25(1):19-25. [PubMed:10685600]
  4. Sinton CM, Fitch TE, Petty F, Haley RW: Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the Rat. Toxicol Appl Pharmacol. 2000 May 15;165(1):99-105. [PubMed:10814558]
  5. Servatius RJ, Ottenweller JE, Guo W, Beldowicz D, Zhu G, Natelson BH: Effects of inescapable stress and treatment with pyridostigmine bromide on plasma butyrylcholinesterase and the acoustic startle response in rats. Physiol Behav. 2000 May;69(3):239-46. [PubMed:10869589]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Somani SM, Husain K, Asha T, Helfert R: Interactive and delayed effects of pyridostigmine and physical stress on biochemical and histological changes in peripheral tissues of mice. J Appl Toxicol. 2000 Jul-Aug;20(4):327-34. [PubMed:10942908]
  2. Servatius RJ, Ottenweller JE, Guo W, Beldowicz D, Zhu G, Natelson BH: Effects of inescapable stress and treatment with pyridostigmine bromide on plasma butyrylcholinesterase and the acoustic startle response in rats. Physiol Behav. 2000 May;69(3):239-46. [PubMed:10869589]
  3. Abou-Donia MB, Wilmarth KR, Abdel-Rahman AA, Jensen KF, Oehme FW, Kurt TL: Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. Fundam Appl Toxicol. 1996 Dec;34(2):201-22. [PubMed:8954750]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Abu-Qare AW, Abou-Donia MB: Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin. Arch Toxicol. 2002 May;76(4):203-8. Epub 2002 Mar 9. [PubMed:12029383]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2018 20:23