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Identification
Name Pralidoxime
Accession Number DB00733 (APRD01193)
Type small molecule
Groups 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Pralidoxime Chloride
Synonyms
Pralidoxime Chloride
Salts Not Available
Brand names
Name Company
ComboPen
Protopam
Brand mixtures Not Available
Categories
  • Antidotes
  • Cholinesterase Reactivators
CAS number 6735-59-7
Weight Average: 137.1592
Monoisotopic: 137.07148792
Chemical Formula C7H9N2O
InChI Key InChIKey=JBKPUQTUERUYQE-UHFFFAOYSA-O
InChI
InChI=1S/C7H8N2O/c1-9-5-3-2-4-7(9)6-8-10/h2-6H,1H3/p+1
Plain Text
IUPAC Name
2-[(1E)-(hydroxyimino)methyl]-1-methylpyridin-1-ium
SMILES
C[N+]1=C(\C=N\O)C=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
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.
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.
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
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • Meridian medical technologies inc
  • Wyeth ayerst laboratories
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intramuscular
Prices
Unit description Cost Unit
Protopam chloride 1 gm vial 104.04 USD tablet
Patents Not Available
Properties
State solid
Melting point 215-225 oC
Experimental Properties
Property Value Source
logP 1.564 PhysProp
Predicted Properties
Property Value Source
water solubility 1.49e-01 g/l ALOGPS
logP -3 ALOGPS
logP -3.3 ChemAxon Molconvert
logS -3.1 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 36.47 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 40.33 ChemAxon Molconvert
polarizability 14.44 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07400 Link_out
BindingDB 50241085 Link_out
ChEBI 8354 Link_out
ChEMBL 8354 Link_out
PharmGKB PA451083 Link_out
Drug Product Database 2043475 Link_out
RxList http://www.rxlist.com/cgi/generic2/pralidoxime.htm Link_out
Drugs.com http://www.drugs.com/mtm/pralidoxime-injection.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Pralidoxime Link_out
ATC Codes
  • V03AB04
AHFS Codes
  • 92:00.00
PDB Entries Not Available
FDA label show (147 KB)
MSDS show (74.1 KB)
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Acetylcholinesterase

Pharmacological action: yes
Actions: activator

Rapidly hydrolyzes choline released into the synapse

Organism class: human
UniProt ID: P22303 Link_out
Gene: ACHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Jokanovic M: Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol Lett. 2009 Oct 28;190(2):107-15. Epub 2009 Aug 3. Pubmed
  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

2. Cholinesterase

Pharmacological action: yes
Actions: activator

An acylcholine + H(2)O = choline + a carboxylate

Organism class: human
UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2012 13:14