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Identification
NamePralidoxime
Accession NumberDB00733  (APRD01193)
TypeSmall Molecule
GroupsApproved, Vet Approved
DescriptionPralidoxime 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 Identifiers
  • NSC 164614
  • UNII-P7MU9UTP52
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Protopam Chlorideinjection, powder, lyophilized, for solution1 g/20mLintramuscular; intravenous; subcutaneousBaxter Healthcare Corporation1965-03-10Not applicableUs
Protopam Chloride - (pws 1g/vial)powder for solution1 gintramuscular; intravenous; subcutaneousWyeth Canada1996-10-252007-05-23Canada
Protopam Chloride Inj 1gmpowder for solution1 gintramuscular; intravenous; subcutaneousAyerst Laboratories1966-12-311997-08-15Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ComboPenNot Available
ContrathionSanofi-Aventis
NispamNeiss
PamclOriental
PamparaSiu Guan
PamuChoong Wae
Pralidoxime ChlorideMeridian
ProtopamBaxter Healthcare Corp.
Brand mixtures
NameLabellerIngredients
DuodoteMeridian Medical Technologies , Inc.
Salts
Name/CASStructureProperties
Pralidoxime Chloride
Thumb
  • InChI Key: HIGSLXSBYYMVKI-UHFFFAOYSA-N
  • Monoisotopic Mass: 172.040340627
  • Average Mass: 172.612
DBSALT000242
Categories
UNIIP7MU9UTP52
CAS number6735-59-7
WeightAverage: 137.1592
Monoisotopic: 137.07148792
Chemical FormulaC7H9N2O
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyridinium derivatives. These are compounds containing a pyridinium ring, which is the cationic form of pyridine.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPyridinium derivatives
Direct ParentPyridinium derivatives
Alternative Parents
Substituents
  • Pyridinium
  • Heteroaromatic compound
  • Aldoxime
  • Azacycle
  • Oxime
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organic cation
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsPralidoxime 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 actionPralidoxime 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNo binding to plasma proteins
Metabolism

Hepatic

Route of eliminationThe drug is rapidly excreted in the urine partly unchanged, and partly as a metabolite produced by the liver.
Half life74-77 minutes
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • Meridian medical technologies inc
  • Wyeth ayerst laboratories
Packagers
Dosage forms
FormRouteStrength
Kitintramuscular
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point215-225 °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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesV03AB04
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (147 KB)
MSDSDownload (74.1 KB)
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

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
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
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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23