Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C7H9N2O.Br |
| Molecular Weight | 217.063 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
| Stereo Comments | Assumed E-isomer as in chloride salt in USP/NF |
SHOW SMILES / InChI
SMILES
[Br-].C[N+]1=C(\C=N\O)C=CC=C1
InChI
InChIKey=UHVXAXRWEJONPZ-UHFFFAOYSA-N
InChI=1S/C7H8N2O.BrH/c1-9-5-3-2-4-7(9)6-8-10;/h2-6H,1H3;1H
| 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 |
| Molecular Formula | BrH |
| Molecular Weight | 80.912 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator'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
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.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL220 |
31.4 µM [Kd] | ||
Target ID: CHEMBL1914 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | PROTOPAM CHLORIDE Approved UsePROTOPAM 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 Date1964 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3988 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20804498 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10070 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20804498 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.94 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20804498 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Dose | Population | Adverse 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) Sources: Thymol turbidity test increased (4 patients) Urobilinogen urine positive (11 patient) Change in ECG (9 patients) |
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 Sources: Headache Visual accommodation disturbance of Epigastric discomfort Vomiting |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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: |
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
Edited
Sat Dec 16 10:42:38 GMT 2023
by
admin
on
Sat Dec 16 10:42:38 GMT 2023
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| Record UNII |
ON33043VUD
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| Record Status |
Validated (UNII)
|
| Record Version |
|
-
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1532-28-1
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admin on Sat Dec 16 10:42:38 GMT 2023 , Edited by admin on Sat Dec 16 10:42:38 GMT 2023
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NON-SPECIFIC STEREOCHEMISTRY | |||
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14018-51-0
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PRIMARY | |||
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ON33043VUD
Created by
admin on Sat Dec 16 10:42:38 GMT 2023 , Edited by admin on Sat Dec 16 10:42:38 GMT 2023
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PRIMARY | |||
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135565168
Created by
admin on Sat Dec 16 10:42:38 GMT 2023 , Edited by admin on Sat Dec 16 10:42:38 GMT 2023
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PRIMARY |
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |