Document Detail

A comparison of cholinergic effects of HI-6 and pralidoxime-2-chloride (2-PAM) in soman poisoning.
MedLine Citation:
PMID:  1998202     Owner:  NLM     Status:  MEDLINE    
The effects of HI-6 and pralidoxime chloride (2-PAM) on soman-induced lethality, time to death and several cholinergic parameters in rats were compared to understand the beneficial action of HI-6. Treatment with atropine sulfate (ATS) or HI-6 alone protected against 1.2 and 2.5 LD50s of soman respectively, whereas 2-PAM or methylated atropine (AMN) alone afforded no protection. Addition of ATS, but not AMN, to HI-6-treated rats enhanced the protection from 2.5 to 5.5 LD50s. HI-6 increased the time-to-death, while 2-PAM had no effect; a combination of HI-6 and ATS provided the most significant increase in time-to-death. Cholinesterase (ChE) activity was not altered in any tissue by ATS, HI-6 or 2-PAM treatment individually, but was markedly inhibited in all tissues by 100 micrograms/kg of soman. In soman-poisoned rats, the HI-6, but not the 2-PAM, group had significantly higher levels of ChE in blood and other peripheral tissues than did the group given soman alone. Neither HI-6 nor 2-PAM affected soman-inhibited ChE in the brain. Additional ATS treatment had no effect on ChE activity. HI-6 and 2-PAM neither modified baseline brain acetylcholine (ACh) or choline (Ch) levels nor protected against soman-induced ACh or Ch elevation. 2-PAM exhibited a 4-fold more potent in vitro inhibition of 3H-quinuclidinyl benzilate (3H-QNB) binding and sodium-dependent high-affinity Ch uptake (HACU) than did HI-6 in brain tissues. The findings that 2-PAM is a more potent in vitro inhibitor of muscarinic receptor binding and HACU than HI-6, and yet neither elevates ChE activity in the periphery nor protects rats against soman poisoning, indicate the importance of higher ChE activity in the periphery of HI-6-treated rats. Maintenance by HI-6 of a certain amount of active ChE in the periphery appears to be important for survival after soman exposure.
T Shih; C E Whalley; J J Valdes
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Toxicology letters     Volume:  55     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  1991 Feb 
Date Detail:
Created Date:  1991-04-01     Completed Date:  1991-04-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  131-47     Citation Subset:  IM    
U.S. Army Medical Research Institute of Chemical Defense Center, Aberdeen Proving Ground, MD.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Acetylcholinesterase / metabolism
Atropine / therapeutic use
Brain / drug effects,  metabolism
Cholinesterase Reactivators / therapeutic use*
Cholinesterases / blood,  metabolism*
Drug Interactions
Lethal Dose 50
Pralidoxime Compounds / therapeutic use*
Pyridinium Compounds / therapeutic use*
Quinuclidinyl Benzilate / metabolism
Rats, Inbred Strains
Receptors, Muscarinic / metabolism
Soman / antagonists & inhibitors,  poisoning*
Reg. No./Substance:
0/Cholinesterase Reactivators; 0/Pralidoxime Compounds; 0/Pyridinium Compounds; 0/Receptors, Muscarinic; 34433-31-3/HI 6; 51-55-8/Atropine; 6581-06-2/Quinuclidinyl Benzilate; 6735-59-7/pralidoxime; 96-64-0/Soman; EC; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Chlorothalonil exposure of workers on mechanical tomato harvesters.
Next Document:  Correlation of changes in serum analytes and hepatic histopathology in rats exposed to carbon tetrac...