You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2014-09-11 05:22:32 UTC
Update Date2014-12-24 20:26:59 UTC
Accession NumberT3D4920
Identification
Common NameParaoxon
ClassSmall Molecule
DescriptionParaoxon is an acetylcholinesterase inhibitor. It is an organophosphate oxon, and the active metabolite of the insecticide parathion. It is also used as an opthamological drug against glaucoma. Paraoxon is one of the most potent acetylcholinesterase-inhibiting insecticides available, around 70% as potent as the nerve agent sarin, and so is now rarely used as an insecticide due to the risk of poisoning to humans and other animals. It is easily absorbed through skin, and was used as an assassination weapon by the apartheid-era South African chemical weapons program Project Coast.
Compound Type
  • Food Toxin
  • Insecticide
  • Metabolite
  • Organic Compound
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
O,O-Diethyl-O-p-nitrophenylphosphoric acid
Chemical FormulaC10H14NO6P
Average Molecular Mass275.195 g/mol
Monoisotopic Mass275.056 g/mol
CAS Registry Number311-45-5
IUPAC Namediethyl 4-nitrophenyl phosphate
Traditional Nameparaoxon
SMILESCCOP(=O)(OCC)OC1=CC=C(C=C1)N(=O)=O
InChI IdentifierInChI=1S/C10H14NO6P/c1-3-15-18(14,16-4-2)17-10-7-5-9(6-8-10)11(12)13/h5-8H,3-4H2,1-2H3
InChI KeyInChIKey=WYMSBXTXOHUIGT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as nitrobenzenes. Nitrobenzenes are compounds containing a nitrobenzene moiety, which consists of a benzene ring with a carbon bearing a nitro group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNitrobenzenes
Direct ParentNitrobenzenes
Alternative Parents
Substituents
  • Nitrobenzene
  • Phenoxy compound
  • Nitroaromatic compound
  • Dialkyl phosphate
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Alkyl phosphate
  • C-nitro compound
  • Organic nitro compound
  • Organic oxoazanium
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point300 °C
Boiling PointNot Available
Solubility3.64 mg/mL at 20 °C
LogP1.98
Predicted Properties
PropertyValueSource
Water Solubility1.44 g/LALOGPS
logP2.05ALOGPS
logP2.43ChemAxon
logS-2.3ALOGPS
pKa (Strongest Basic)-9.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area90.58 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity64.7 m³·mol⁻¹ChemAxon
Polarizability24.97 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4m-4910000000-9e80686be84777f12897JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4m-4910000000-9e80686be84777f12897JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01ot-1490000000-49af8e137482487310cbJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-00di-1490000000-8d48b56d5d32ad4f5d91JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-1290000000-6438528767f006512903JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0gb9-0090000000-775108cc711fdc42be34JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-7900000000-0b2814cb44352b4577e1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0190000000-cfd94300e89fae9a0128JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-1490000000-609dc6a1aa30dd298795JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00fr-2940000000-ab53630a454ec7edd2b2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dj-0090000000-4a26b1cf19be9be1c3a4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0090000000-e9fc319d73d2521066baJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-3940000000-a73e447d3d81875336b5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00e9-0090000000-d817a293e17ff8d661c9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0960000000-d7e8a3a00ae9564d521dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pb9-2910000000-8234e0a0630a65f206b4JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-054k-9840000000-ed91d6d60187378e30e6JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityParaoxon is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismMetabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsSymptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB13035
PubChem Compound ID9395
ChEMBL IDNot Available
ChemSpider ID9026
KEGG IDC06606
UniProt IDNot Available
OMIM ID
ChEBI ID27827
BioCyc IDPARAOXON
CTD IDD010261
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkParaoxon
References
Synthesis ReferenceNot Available
MSDST3D4920.pdf
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Cation transmembrane transporter activity
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name:
CHRNE
Uniprot ID:
Q04844
Molecular Weight:
54696.54 Da
References
  1. Radic Z, Sit RK, Garcia E, Zhang L, Berend S, Kovarik Z, Amitai G, Fokin VV, Barry Sharpless K, Taylor P: Mechanism of interaction of novel uncharged, centrally active reactivators with OP-hAChE conjugates. Chem Biol Interact. 2013 Mar 25;203(1):67-71. doi: 10.1016/j.cbi.2012.08.014. Epub 2012 Sep 4. [22975155 ]
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Peeples ES, Schopfer LM, Duysen EG, Spaulding R, Voelker T, Thompson CM, Lockridge O: Albumin, a new biomarker of organophosphorus toxicant exposure, identified by mass spectrometry. Toxicol Sci. 2005 Feb;83(2):303-12. Epub 2004 Nov 3. [15525694 ]
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508 uMTox21_Aromatase_InhibitionTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.52 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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. Petroianu G, Kuhn F, Thyes C, Ewald V, Missler A: In vitro protection of plasma cholinesterases by metoclopramide from inhibition by paraoxon. J Appl Toxicol. 2003 Jan-Feb;23(1):75-9. [12518340 ]