U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C7H9N2O.CH3O3S
Molecular Weight 232.257
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PRALIDOXIME MESYLATE

SMILES

CS([O-])(=O)=O.C[N+]1=C(\C=N\O)C=CC=C1

InChI

InChIKey=WWZYJJGFUIAWNW-UHFFFAOYSA-N
InChI=1S/C7H8N2O.CH4O3S/c1-9-5-3-2-4-7(9)6-8-10;1-5(2,3)4/h2-6H,1H3;1H3,(H,2,3,4)

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C7H8N2O
Molecular Weight 136.1512
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00733 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21175_Atnaa_prntlbl.pdf | http://reference.medscape.com/drug/protopam-2pam-antidote-pralidoxime-343744 | https://www.ncbi.nlm.nih.gov/pubmed/27450532

Pralidoxime is a cholinesterase reactivator used as the antidote to organophosphate pesticides or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam. 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. Pralidoxime is indicated as an adjunct in the treatment of moderate and severe poisoning caused by organophosphate pesticides that have anticholinesterase activity or by chemicals with anticholinesterase activity such as some chemicals used as nerve agents during chemical warfare. Pralidoxime is also indicated as an adjunct in the management of the overdose of cholinesterase inhibitors, such as ambenonium, neostigmine, and pyridostigmine, used in the treatment of myasthenia gravis. Pralidoxime, used in conjunction with atropine, reverses nicotinic effects, such as muscle weakness and fasciculation, respiratory depression, and central nervous system (CNS) effects, associated with toxic exposure to organophosphate anticholinesterase pesticides and chemicals and with cholinesterase inhibitor overdose. Atropine, by antagonizing the action of cholinesterase inhibitors at muscarinic receptor sites, reverses muscarinic effects, such as tracheobronchial and salivary secretion, bronchoconstriction, bradycardia, and, to a moderate extent, CNS effects.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
31.4 µM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
PROTOPAM CHLORIDE

Approved Use

PROTOPAM Chloride is indicated as an antidote: 1.In the treatment of poisoning due to those pesticides and chemicals (e.g., nerve agents) of the organophosphate class which have anticholinesterase activity and 2.In the control of overdosage by anticholinesterase drugs used in the treatment of myasthenia gravis. The principal indications for the use of PROTOPAM Chloride are muscle weakness and respiratory depression. In severe poisoning, respiratory depression may be due to muscle weakness.

Launch Date

-1.83254401E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3988 ng/mL
700 mg single, intramuscular
dose: 700 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.5 μg/mL
1000 mg single, intramuscular
dose: 1000 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
9.9 μg/mL
1000 mg single, intramuscular
dose: 1000 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10070 ng × h/mL
700 mg single, intramuscular
dose: 700 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.94 h
700 mg single, intramuscular
dose: 700 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3 h
1000 mg single, intramuscular
dose: 1000 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
3 h
1000 mg single, intramuscular
dose: 1000 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
1000 mg single, intramuscular
dose: 1000 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
PRALIDOXIME plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2000 g 2 times / day multiple, oral
Dose: 2000 g, 2 times / day
Route: oral
Route: multiple
Dose: 2000 g, 2 times / day
Sources:
healthy, adult
n = 29
Health Status: healthy
Age Group: adult
Population Size: 29
Sources:
Other AEs: Lymphocytosis, Thymol turbidity test increased...
Other AEs:
Lymphocytosis (5 patients)
Thymol turbidity test increased (4 patients)
Urobilinogen urine positive (11 patient)
Change in ECG (9 patients)
Sources:
4 g single, oral
Dose: 4 g
Route: oral
Route: single
Dose: 4 g
Sources:
healthy, adult
n = 10
Health Status: healthy
Age Group: adult
Population Size: 10
Sources:
45 mg/kg single, intramuscular
Dose: 45 mg/kg
Route: intramuscular
Route: single
Dose: 45 mg/kg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
45 mg/kg single, intravenous
Dose: 45 mg/kg
Route: intravenous
Route: single
Dose: 45 mg/kg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
Other AEs: Hypertension, Headache...
Other AEs:
Hypertension
Headache
Visual accommodation disturbance of
Epigastric discomfort
Vomiting
Sources:
AEs

AEs

AESignificanceDosePopulation
Urobilinogen urine positive 11 patient
2000 g 2 times / day multiple, oral
Dose: 2000 g, 2 times / day
Route: oral
Route: multiple
Dose: 2000 g, 2 times / day
Sources:
healthy, adult
n = 29
Health Status: healthy
Age Group: adult
Population Size: 29
Sources:
Thymol turbidity test increased 4 patients
2000 g 2 times / day multiple, oral
Dose: 2000 g, 2 times / day
Route: oral
Route: multiple
Dose: 2000 g, 2 times / day
Sources:
healthy, adult
n = 29
Health Status: healthy
Age Group: adult
Population Size: 29
Sources:
Lymphocytosis 5 patients
2000 g 2 times / day multiple, oral
Dose: 2000 g, 2 times / day
Route: oral
Route: multiple
Dose: 2000 g, 2 times / day
Sources:
healthy, adult
n = 29
Health Status: healthy
Age Group: adult
Population Size: 29
Sources:
Change in ECG 9 patients
2000 g 2 times / day multiple, oral
Dose: 2000 g, 2 times / day
Route: oral
Route: multiple
Dose: 2000 g, 2 times / day
Sources:
healthy, adult
n = 29
Health Status: healthy
Age Group: adult
Population Size: 29
Sources:
Epigastric discomfort
45 mg/kg single, intravenous
Dose: 45 mg/kg
Route: intravenous
Route: single
Dose: 45 mg/kg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
Headache
45 mg/kg single, intravenous
Dose: 45 mg/kg
Route: intravenous
Route: single
Dose: 45 mg/kg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
Hypertension
45 mg/kg single, intravenous
Dose: 45 mg/kg
Route: intravenous
Route: single
Dose: 45 mg/kg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
Visual accommodation disturbance of
45 mg/kg single, intravenous
Dose: 45 mg/kg
Route: intravenous
Route: single
Dose: 45 mg/kg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
Vomiting
45 mg/kg single, intravenous
Dose: 45 mg/kg
Route: intravenous
Route: single
Dose: 45 mg/kg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim
PubMed

PubMed

TitleDatePubMed
The reactivation by oximes and hydroxamic acids of cholinesterase inhibited by organo-phosphorus compounds.
1955 Dec
Patents

Patents

Sample Use Guides

1-2 g IV infusion (10-20 mg/mL) over 15-30 min, repeat in 1 hr if necessary and repeat q12hr thereafter PRN; if not practical or if pulmonary edema present or fluid restriction necessary administer as 50 mg/mL over 5 min; a second bolus of 1-2 g may be indicated after about 1 hr if muscle weakness has not been relieved; may repeat q10-12hr prn Alternatively, administer 30 mg/kg IV (IM, SC if no IV access) over 20 min; follow by 4-8 mg/kg/hr maintenance IV infusion Use with atropine, which affects muscarinic receptors; pralidoxime's actions most striking at nicotonic sites (increase muscle strength 10-40 min) IM: 600 mg IM x3 doses; administer each dose 15 minutes apart for mild symptoms, or in rapid succession for severe symptoms; not to exceed 1800 mg total dose initially; if symptoms persist may repeat series of three injections 1 hr after last injection
Route of Administration: Other
The stock solutions of the nerve agents, sarin and VX were prepared freshly in 2-propanol and stored under refrigeration. Appropriate quantity of the individual NA (sarin and VX) was added to the suspension of enzyme hAChE in phosphate buffer at 37 C and incubated for ten minutes to achieve 95–98% inhibition of the control activity. The oxime (Pralidoxime) solution of particular concentration (1.0–0.01 mkM) was added to the nerve agent inhibited hAChE and the reactivation profile was monitored over the time period of sixty minutes at different time intervals. Spontaneous reactivation of the inhibited hAChE was determined using the same protocol (reaction mixture containing enzyme and OP but no oxime), but the spontaneous reactivation was found to be insignificant. All the values were corrected for their oxime induced hydrolysis of ATChI.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:37:10 UTC 2023
Edited
by admin
on Fri Dec 15 15:37:10 UTC 2023
Record UNII
45CO7XIN2K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PRALIDOXIME MESYLATE
MI   USAN  
USAN  
Official Name English
PRALIDOXIME MESYLATE [USAN]
Common Name English
PRALIDOXIME METHANE SULPHONATE
Common Name English
PRALIDOXIME MESILATE [MART.]
Common Name English
PRALIDOXIME MESYLATE [MI]
Common Name English
PRALIDOXIME MESILATE
MART.   WHO-DD  
Common Name English
PRALIDOXIME METHANESULFONATE
Common Name English
Pralidoxime mesilate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47796
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C73848
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
EVMPD
SUB45388
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
EPA CompTox
DTXSID40858961
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
PUBCHEM
65349
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
ECHA (EC/EINECS)
205-839-8
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
CAS
105404-71-5
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
CAS
154-97-2
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
NON-SPECIFIC STEREOCHEMISTRY
MESH
C028797
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
RXCUI
55053
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY RxNorm
MERCK INDEX
m9092
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY Merck Index
ChEMBL
CHEMBL1420
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
FDA UNII
45CO7XIN2K
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
SMS_ID
100000131431
Created by admin on Fri Dec 15 15:37:10 UTC 2023 , Edited by admin on Fri Dec 15 15:37:10 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY