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Details

Stereochemistry ACHIRAL
Molecular Formula C7H9N2O.I
Molecular Weight 264.0636
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0
Stereo Comments Assumed E-isomer (MM2 minimum energy for E and Z isomers of moieties are 9.9968 and 13.3275 kcal/mol)

SHOW SMILES / InChI
Structure of PRALIDOXIME IODIDE

SMILES

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

InChI

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

HIDE SMILES / InChI

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

1964
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.
Name Type Language
PRALIDOXIME IODIDE
INN   JAN   MART.   USAN   WHO-DD  
USAN   INN  
Official Name English
2-Formyl-1-methylpyridinium iodide oxime
Systematic Name English
PRALIDOXIME IODIDE [JAN]
Common Name English
1-METHYL-2-HYDROXYIMINOETHYLPYRIDINIUM IODIDE
Systematic Name English
NSC-7760
Code English
NSC-40164
Code English
Pralidoxime iodide [WHO-DD]
Common Name English
PRALIDOXIME IODIDE [MART.]
Common Name English
PRALIDOXIME IODIDE [USAN]
Common Name English
PRALIDOXIME IODIDE [MI]
Common Name English
pralidoxime iodide [INN]
Common Name English
PAM
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C47796
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
Code System Code Type Description
FDA UNII
7H254VC0NT
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
NCI_THESAURUS
C73847
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
NSC
40164
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
CHEBI
32038
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
INN
851
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
SMS_ID
100000081393
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
ChEMBL
CHEMBL1420
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
CAS
74070-01-2
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
ALTERNATIVE
PUBCHEM
65342
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
ECHA (EC/EINECS)
202-349-6
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
NSC
7760
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
RXCUI
55052
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY RxNorm
EVMPD
SUB09988MIG
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
MESH
C028797
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
EPA CompTox
DTXSID80916716
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY
CAS
94-63-3
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
NON-SPECIFIC STEREOCHEMISTRY
MERCK INDEX
m9092
Created by admin on Fri Dec 15 15:49:11 GMT 2023 , Edited by admin on Fri Dec 15 15:49:11 GMT 2023
PRIMARY Merck Index