Identification

Name
Pralidoxime
Accession Number
DB00733  (APRD01193)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Pralidoxime is an antidote to organophosphate pesticides and chemicals. Organophosphates bind to the esteratic site of acetylcholinesterase, which results initially in reversible inactivation of the enzyme. If given within 24 hours,after organophosphate exposure, pralidoxime reactivates the enzyme cholinesterase by cleaving the phosphate-ester bond formed between the organophosphate and acetylcholinesterase.

Structure
Thumb
Synonyms
  • 2-PAM
  • Pralidoxim
  • Pralidoxima
  • Pralidoxime
  • Pralidoximum
External IDs
NSC 164614
Product Ingredients
IngredientUNIICASInChI Key
Pralidoxime chloride8ZGS5FTO5L51-15-0HIGSLXSBYYMVKI-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pralidoxime ChlorideInjection600 mg/2mLIntramuscularMeridian Medical Technologies , Inc.1983-04-26Not applicableUs
Protopam ChlorideInjection, powder, lyophilized, for solution1 g/20mLIntramuscular; Intravenous; SubcutaneousBaxter Laboratories1965-03-10Not applicableUs
Protopam Chloride - (pws 1g/vial)Powder, for solution1 gIntramuscular; Intravenous; SubcutaneousWyeth Ltd.1996-10-252007-05-23Canada
Protopam Chloride Inj 1gmPowder, for solution1 gIntramuscular; Intravenous; SubcutaneousAyerst Laboratories1966-12-311997-08-15Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ATNAA atropine and pralidoxime chloride Auto-InjectorPralidoxime chloride (600 mg/2mL) + Atropine (2.1 mg/0.7mL)KitIntramuscularMeridian Medical Technologies, Inc.2002-01-17Not applicableUs
DuoDotePralidoxime chloride (600 mg/2mL) + Atropine (2.1 mg/0.7mL)KitIntramuscularMeridian Medical Technologies, Inc.2006-09-28Not applicableUs
International/Other Brands
ComboPen / Contrathion (Sanofi-Aventis) / Nispam (Neiss) / Pamcl (Oriental) / Pampara (Siu Guan) / Pamu (Choong Wae) / Pralidoxime Chloride (Meridian) / Protopam (Baxter Healthcare Corp.)
Categories
UNII
P7MU9UTP52
CAS number
6735-59-7
Weight
Average: 137.1592
Monoisotopic: 137.07148792
Chemical Formula
C7H9N2O
InChI Key
JBKPUQTUERUYQE-UHFFFAOYSA-O
InChI
InChI=1S/C7H8N2O/c1-9-5-3-2-4-7(9)6-8-10/h2-6H,1H3/p+1
IUPAC Name
2-[(1E)-(hydroxyimino)methyl]-1-methylpyridin-1-ium
SMILES
C[N+]1=C(\C=N\O)C=CC=C1

Pharmacology

Indication

For the treatment of poisoning due to those pesticides and chemicals of the organophosphate class which have anticholinesterase activity and in the control of overdosage by anticholinesterase drugs used in the treatment of myasthenia gravis.

Associated Conditions
Pharmacodynamics

Pralidoxime is to reactivate cholinesterase (mainly outside of the central nervous system) which has been inactivated by phosphorylation due to an organophosphate pesticide or related compound. The destruction of accumulated acetylcholine can then proceed, and neuromuscular junctions will again function normally. Pralidoxime also slows the process of "aging" of phosphorylated cholinesterase to a nonreactivatable form, and detoxifies certain organophosphates by direct chemical reaction. The drug has its most critical effect in relieving paralysis of the muscles of respiration. Because pralidoxime is less effective in relieving depression of the respiratory center, atropine is always required concomitantly to block the effect of accumulated acetylcholine at this site. Pralidoxime relieves muscarinic signs and symptoms, salivation, bronchospasm, etc., but this action is relatively unimportant since atropine is adequate for this purpose.

Mechanism of action

Pralidoxime is an antidote to organophosphate pesticides and chemicals. Organophosphates bind to the esteratic site of acetylcholinesterase, which results initially in reversible inactivation of the enzyme. Acetylcholinesterase inhibition causes acetylcholine to accumulate in synapses, producing continuous stimulation of cholinergic fibers throughout the nervous systems. If given within 24 hours after organophosphate exposure, pralidoxime reactivates the acetylcholinesterase by cleaving the phosphate-ester bond formed between the organophosphate and acetylcholinesterase.

TargetActionsOrganism
AAcetylcholinesterase
activator
Human
ACholinesterase
activator
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

No binding to plasma proteins

Metabolism

Hepatic

Route of elimination

The drug is rapidly excreted in the urine partly unchanged, and partly as a metabolite produced by the liver.

Half life

74-77 minutes

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

Interactions

Drug Interactions
DrugInteraction
AbacavirPralidoxime may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Pralidoxime which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Pralidoxime which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Pralidoxime which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Pralidoxime which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Pralidoxime which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Pralidoxime which could result in a higher serum level.
AclidiniumPralidoxime may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastinePralidoxime may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Pralidoxime which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014871
KEGG Compound
C07400
PubChem Compound
5353894
PubChem Substance
46509152
ChemSpider
5193737
BindingDB
234367
ChEBI
8354
ChEMBL
CHEMBL1420
PharmGKB
PA164744926
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pralidoxime
ATC Codes
V03AB04 — Pralidoxime
FDA label
Download (147 KB)
MSDS
Download (74.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentThe Mortality Rate1
3CompletedTreatmentOrganophosphate Poisoning1
Not AvailableCompletedTreatmentAcute Organophosphorus Pesticide Poisoning1

Pharmacoeconomics

Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • Meridian medical technologies inc
  • Wyeth ayerst laboratories
Packagers
  • Baxter International Inc.
  • Meridian Medical Technologies Inc.
Dosage forms
FormRouteStrength
KitIntramuscular
InjectionIntramuscular600 mg/2mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Subcutaneous1 g/20mL
Powder, for solutionIntramuscular; Intravenous; Subcutaneous1 g
Prices
Unit descriptionCostUnit
Protopam chloride 1 gm vial104.04USD tablet
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)215-225 °CNot Available
logP1.564Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.149 mg/mLALOGPS
logP-3ALOGPS
logP-3.3ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)5.78ChemAxon
pKa (Strongest Basic)-1.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area36.47 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity40.33 m3·mol-1ChemAxon
Polarizability14.44 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8407
Blood Brain Barrier+0.9544
Caco-2 permeable+0.6113
P-glycoprotein substrateNon-substrate0.7408
P-glycoprotein inhibitor INon-inhibitor0.9154
P-glycoprotein inhibitor IINon-inhibitor0.9824
Renal organic cation transporterNon-inhibitor0.7049
CYP450 2C9 substrateNon-substrate0.7624
CYP450 2D6 substrateNon-substrate0.8025
CYP450 3A4 substrateNon-substrate0.6683
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9463
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9289
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9238
Ames testNon AMES toxic0.7247
CarcinogenicityNon-carcinogens0.7872
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity2.4000 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8628
hERG inhibition (predictor II)Non-inhibitor0.858
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
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0900000000-20fdfd5334ead907481e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00kr-1900000000-28213070bfa027f76396
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00kf-9600000000-e526d65f27b45380a401
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9100000000-5b6d1f4a0b4b4f3b44d8
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014l-9000000000-dcac00013d3eaf2dd6d9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00ko-4900000000-030938e55f082376a8fc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00kf-9200000000-7ee2419716b3f943ce85

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 / Aldoximes / Azacyclic compounds / Organopnictogen compounds / Organic oxygen compounds / Hydrocarbon derivatives / Organic cations
Substituents
N-methylpyridinium / Pyridinium / Heteroaromatic compound / Aldoxime / Azacycle / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyridinium ion (CHEBI:8354)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Activator
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. Jokanovic M, Prostran M: Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds. Curr Med Chem. 2009;16(17):2177-88. [PubMed:19519385]
  2. Kovacic P: Mechanism of organophosphates (nerve gases and pesticides) and antidotes: electron transfer and oxidative stress. Curr Med Chem. 2003 Dec;10(24):2705-9. [PubMed:14529460]
  3. Jokanovic M: Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol Lett. 2009 Oct 28;190(2):107-15. doi: 10.1016/j.toxlet.2009.07.025. Epub 2009 Aug 3. [PubMed:19651196]
  4. Wong L, Radic Z, Bruggemann RJ, Hosea N, Berman HA, Taylor P: Mechanism of oxime reactivation of acetylcholinesterase analyzed by chirality and mutagenesis. Biochemistry. 2000 May 16;39(19):5750-7. [PubMed:10801325]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Activator
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. Pohanka M, Jun D, Kuca K: In vitro reactivation of trichlorfon-inhibited butyrylcholinesterase using HI-6, obidoxime, pralidoxime and K048. J Enzyme Inhib Med Chem. 2009 Jun;24(3):680-3. doi: 10.1080/14756360802328315. [PubMed:18825528]
  2. Khan S, Hemalatha R, Jeyaseelan L, Oommen A, Zachariah A: Neuroparalysis and oxime efficacy in organophosphate poisoning: a study of butyrylcholinesterase. Hum Exp Toxicol. 2001 Apr;20(4):169-74. [PubMed:11393267]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 07:03